CN101522908A - Modified microbial nucleic acid for use in detection and analysis of microorganisms - Google Patents

Abstract

The present invention provides derivatives or modified nucleic acid sequences of several microorganisms for use in the detection and analysis of said microorganisms. The derivative nucleic acids contain the bases adenosine (A), guanosine (G), T (thymine) and U (uracil or some other non-A, G or T base or base-like entity). Given that microbial nucleic acids do not contain methylated cytosine (C) orother C alterations, all C are converted to U. These sequences are amplified where the U in the derivative nucleic acid is replaced by a T, resulting in a modified sequence with the same number of to tal bases as the corresponding unmodified microbial nucleic acid sequence but made up of a combination of three bases only: A, G and T. As a consequence of this process the nucleic acids derived from the upper and lower strands of the original dsDNA are no longer complementary and the modified microbial sequences have reduced relative genomic complexity for use in detection and analysis of microorganisms.

Description

The microorganism modification of nucleic acids that is used for microorganism detection and analysis

Technical field

The present invention relates to be used to detect and analyze the modification of nucleic acids of microorganism.

Background technology

There is the multiple method that is used to detect the specific nucleic acid molecule at present.These methods depend on the sequence dependent hybridization between target nucleic acid and nucleic acid probe usually, and the length of described nucleic acid probe can be from short oligonucleotide (20 base or still less) to changing between the thousands of bases (kb).

The most popular method of amplification particular sequence is polymerase chain reaction (PCR) (Dieffenbach from the nucleotide sequence group, C and Dveksler, G.eds.PCR Primer:A Laboratory Manual.ColdSpring Harbor Press, Plainview NY).In this amplification method, utilize length on the complementary dna chain to be generally 20 to 30 Nucleotide and be positioned at the terminal arbitrarily oligonucleotide in zone to be amplified, on the sex change single stranded DNA, cause the synthetic of DNA.Sex change, primer hybridization and utilize the continuous circulation of thermostability archaeal dna polymerase synthetic DNA chain can realize the index amplification of sequence between primer.Can use reverse transcription to produce complementary DNA (cDNA) copy, to copy cloning RNA by first.Can survey the dna fragmentation of amplification by several different methods, comprise gel electrophoresis, with the probe hybridization of mark, use can be carried out the primer (for example surveying by the enzyme joint inspection) of the tape label of follow-up evaluation, and the primer that can produce the band fluorescence labels of signal after use and the target DNA hybridization.

Except PCR, also developed other and multiplely be used to detect and the technology of the specific nucleic acid sequence that increases.Example be ligase chain reaction (1991, Barany, F.et al., Proc.Natl.Acad.Sci.USA88,189-193).

Another example is isothermal duplication (the Walker GT that set forth first in 1992, Little MC, Nadeau JG and Shank D.Isothermal in vitro amplification of DNA by arestriction enzyme/DNA polymerase system.PNAS 89:392-396 (1992)), also be known as strand displacement amplification (SDA).Many other isothermal amplification techniques appear again thereafter, comprise the amplification (TMA) of transcriptive intermediate, and utilize RNA polymerase replicated rna sequence but not the amplification based on nucleotide sequence (NASBA) (the Guatelli JC of corresponding gene group DNA, Whitfield KM, Kwoh DY, BarringerKJ, Richmann DD and Gingeras TR.Isothermal, in vitro amplification of nucleicacids by a multienzyme reaction modeled after retroviral replication.PNAS 87:1874-1878 (1990); Kievits T, van Gemen B, van Strijp D, Schukkink R, Dircks M, Adriaanse H, Malek L, Sooknanan R, Lens P.NASBA isothermal enzymatic invitro nucleic acid amplification optimized for the diagnosis of HIV-1 infection.JVirol Methods.1991Dec; 35 (3): 273-86).

Other temperature technique that waits based on DNA comprises: use archaeal dna polymerase to extend the rolling circle amplification (RCA) (Fire A and Xu SQ.Rolling replication of short circles.PNAS92:4641-4645 (1995)) of the primer of target circular template, cycling probe is used for netted branch augmentation (RAM) (the Zhang W that target detects, Cohenford M, Lentrichia B, Isenberg HD, Simson E, Li H, YiJ, Zhang DY.Detection of Chlamydia trachomatis by isothermal ramificationamplification method:a feasibility study.J Clin Microbiol.2002 Jan; 40 (1): 128-32.), and use helicase to replace helicase dependent isothermal dna amplification (HAD) (Vincent M that heat is unwind DNA recently, Xu Y, Kong H.Helicase-dependent isothermalDNA amplification.EMBO Rep.2004 Aug; 5 (8): 795-800).

Recently, set forth isothermal method (the Walker GT of DNA cloning, Little MC, Nadeau JG andShank D.Isothermal in vitro amplification of DNA by a restriction enzyme/DNApolymerase system.PNAS 89:392-396 (1992)).Traditional amplification technique depends on the continuous circulation of target molecules sex change and renaturation in each circulation of amplified reaction.The thermal treatment of DNA can cause dna molecular shearing (shearing) to a certain degree, therefore, when DNA for example is limited at from a few cell of growing blastaea DNA isolation, be that this heating-refrigeration cycle may further be destroyed DNA and cause losing of amplified signal under the situation of fragmentation form (for example DNA in tissue slice, paraffin mass and outmoded dna sample) at DNA especially perhaps.The lasting sex change that isothermal method does not rely on template DNA to be producing as the further single chain molecule of the template of amplification, but depends under steady temperature special restriction endonuclease to the enzymatic nicking (nicking) of dna molecular.

The technology that is called as strand displacement amplification (SDA) depends in specific limited enzyme nicking half modifying DNA ability of modified chain not and lacks the polymerase extension of 5 '-3 ' exonuclease activity and replace the ability of downstream chain.Subsequently, react and the antisense reaction with coupling justice as the template of antisense reaction by the displacement chain that will be obtained from the justice reaction, thereby realize index amplification (Walker GT, Little MC, Nadeau JGand Shank D.Isothermal in vitro amplification of DNA by a restrictionenzyme/DNA polymerase system.PNAS 89:392-396 (1992)).This type of technology mycobacterium tuberculosis (Mycobacterium tuberculosis) (Walker GT that has been used for successfully increasing, LittleMC, Nadeau JG and Shank D.Isothermal in vitro amplification of DNA by arestriction enzyme/DNA polymerase system.PNAS89:392-396 (1992), HIV-1, Hepatitis Cand HPV-16 Nuovo G.J., 2000), chlamydia trachomatis (Chlamydiatrachomatis) (Spears PA, Linn P, Woodard DL and Walker GT.SimultaneousStrand Displacement Amplification and Fluorescence Polarization Detection ofChlamydia trachomatis.Anal.Biochem.247:130-137 (1997)).

The application-dependent of SDA is in modifying thiophosphatephosphorothioate Nucleotide to produce half phosphorothioate dna two strands at present, and its modification chain will have resistance to the shearing of enzyme, drive replacement(metathesis)reaction thereby produce the enzymatic nicking but not degrade.Yet, utilize genetically engineered to produce multiple " nickase " recently.These enzymes are cutting DNA in a conventional manner not, but produces otch on the chain of DNA." nickase " comprises N.Alw1 (Xu Y, Lunnen KD and Kong H.Engineering a nicking endonucleaseN.Alwl by domain swapping.PNAS98:12990-12995 (2001)), N.BstNB1 (Morgan RD, Calvet C, Demeter M, Agra R, Kong H.Characterization of thespecific DNA nicking activity of restriction endonuclease N.BstNBI.Biol Chem.2000 Nov; 381 (11): 1123-5) and Mlyl (Besnier CE, Kong H.Converting MlyIendonuclease into a nicking enzyme by changing its oligomerization state.EMBORep.2001 Sep; 2 (9): 782-6.Epub 2001 Aug 23).Therefore, use this fermentoid can simplify the SDA method.

In addition, now improve SDA by the combination of using heat-staple Restriction Enzyme (Aval) and heat-staple circumscribed polysaccharase (exo-polymerase) (Bst polysaccharase).Verified this combination can with the reaction amplification efficiency from 10 ⁸Doubly amplification is increased to 10 ¹⁰Doubly amplification is so use single copy molecule that it is unique that this technology may increase.Using the amplification factor that the heat-stabilised poly synthase/the enzyme combination is produced is 10 ⁹The order of magnitude (Milla M.A., Spears P.A., Pearson R.E.and Walker G.T.Use of theRestriction Enzyme Ava l and Exo-Bst Polymerase in Strand DisplacementAmplification Biotechniques 1997 24:392-396).

At present, all isothermal dna amplification techniques all need make the sex change of initial double-stranded template dna molecular before the amplification beginning.In addition, each firing event only can initiate once to increase.

For direct detection, modal is to come a minute isolated target nucleic acid by gel electrophoresis according to size, and (Southern and Northern hybridization) is preceding to be transferred to target nucleic acid on the solid support hybridizing with the probe of target complement sequence.Probe can be natural acid or analogue, for example peptide nucleic acid(PNA) (PNA) or lock nucleic acid (LNA) or imbedibility nucleic acid (INA).Can use direct mark probe (for example by ³²The P mark), also can use Indirect Detecting Method.Indirect method depends on usually in probe introduces one " label " as vitamin H or digoxin, subsequently by join as enzyme substrate conversion or chemiluminescent method detect as described in probe.

Another the widely used method that is used for directly detecting nucleic acid is " sandwich " hybridization.In this method, capture probe is coupled on the solid support, and makes target nucleic acid and bonded probe hybridization in the solution.The unconjugated target nucleic acid of flush away, and second probe of utilization and target sequence hybridization detects bonded nucleic acid.Can use the direct or indirect method of above summary to detect.The example of these class methods comprise " branched DNA " signal detection system of using the sandwich hybridization principle (1991, Urdea, M.S., et al., Nucleic Acids Symp.Ser.24,197-200).The field that utilizes nucleic acid hybridization directly to detect a fast development of nucleotide sequence be dna microarray (2002, Nature Genetics, 32, [Supplement]; 2004, Cope, L.M., et al., Bioinformatics, 20,323-331; 2004, Kendall, S.L., et al., Trends in Microbiology, 12,537-544).In this method, with short chain oligonucleotide (in the Affymetrix system, being generally 25-mers) to long-chain oligonucleotide (in Applied Biosystems and Agilent platform, being generally 60-mers), even the nucleic acid molecule individuality in longer sequence (for example cDNA clone) scope is fixed on the reticulation solid support or on solid support photoetching synthetic.Carry out quantitatively subsequently with tape label or the nucleic acid group and the hybridization array that are labeled, and to the hybridization level of each point in this array.Though can use as chemiluminescent other detection system, more normal use is radio-labeling or fluorescently-labeled nucleic acid (for example cRNA or cDNA) in the hybridization.

The field that utilizes nucleic acid hybridization directly to detect a fast development of nucleotide sequence is dna microarray (Young RA Biomedical discovery with DNA arrays.Cell 102:9-15 (2000); Watson A New tools.A new breed of hightech detectives.Science 289:850-854 (2000)).In this method, oligonucleotide to the nucleic acid molecule individuality in longer sequence (for example complementary DNA (cDNA) clone) scope is fixed on the reticulation solid support.Carry out quantitatively subsequently with tape label or the nucleic acid group and the hybridization array that are labeled, and to the hybridization level of each point in this array.Though can use other detection system, more normal use is radio-labeling or fluorescently-labeled nucleic acid (for example cDNA) in the hybridization.

The traditional method that detects microorganism (for example bacterium, yeast and fungi) is included in and cultivates described microorganism on the selectivity nutritional medium, produces, as the feature of biochemistry or enzymatic reaction and special dyeing property (for example gramstaining) microorganism is classified according to observed size under conventional opticmicroscope, shape, spore subsequently.Viral species must be cultivated in the tissue of specialization or cell, according to its structure determined by electron microscope and size described virus is classified subsequently.A main drawback of this technology is that not all microorganism can both grow under conventional culture condition or cell condition, thereby has limited the application of these class methods.For example, for bacterium, for example Neisseria meningitidis (Neisseriameningitidis), streptococcus pneumoniae (Streptococcus pneumoniae) and hemophilus influenzae (Haemophilus influenzae) (can both cause meningitis, and wherein Neisseria meningitidis causing meningitis and acute cerebral meningitis coccus microbemia simultaneously) all are difficult to for these three kinds cultivate.For Blood culture bottle, in 7 days, carry out routine examination every day, and the cultivation of need going down to posterity.Hemophilus influenzae need comprise the special culture medium of Reduced nicotinamide-adenine dinucleotide and protohemine and cultivate on the Chocolate Agar flat board.Hemoculture needs trypticase soybean broth or brain heart infusion, and needs to add multiple additives, for example poly-methyl allylphenol sodium sulfonate.For microorganism, for example cause the Clostridium botulinum (Clostridium botulinum) of the soft syndrome of serious food poisoning and baby (floppybaby syndrome), the evaluation of toxin comprises to injected in mice food extract or culture supernatant, and after 2 days observations.In addition, on special culture medium, cultivate potential microorganism and need a week.Can absorb or in several minutes, detect streptococcus aureus (Staphylococcus aureus) enterotoxin (cause of food poisoning and skin infections, blood infection, pneumonia, osteomyelitis, sacroiliitis and cerebral abscess) in the selectivity when the ion exchange resin by toxin by the reverse passive latex agglutination (Reverse Passive LatexAgglutination) that utilizes monoclonal antibody.The staphylococcus epidermidis close with it (S.epidermis) causes blood infection and pollutes equipment and surface and the health care machine and the utensil of hospital.

Non-viral micro-organisms can also be classified according to its metabolic characteristic, for example utilizing the substrate as glucose, maltose or sucrose to carry out in the fermentation reaction process, produces special amino acid or metabolite.Also can carry out somatotype to antibiotic susceptibility to microorganism according to it.Also use at the specific antibody of cell-surface antigens or secretory protein (for example toxin) and differentiate microorganism or it is carried out somatotype.Yet, more than all methods all depend on the cultivation of the microorganism before detecting.The cultivation of microorganism consumption money is consuming time, and also may take place to pollute or overgrowth when cultivating the not too harsh microorganism of nutritional condition.This type of technology is also very unripe, therefore need carry out a plurality of detections to obtain definite diagnostic result on same sample.When the typical hybrid colony of different types of microorganisms is present in the wild sample or when relevant with higher organism, because most of microbe all is not easy growth in known substratum, so can not reach detection level.

The method of other detection or evaluation pathogenic micro-organism is based on the serology approach of antibody with the response infected by microbes that produce.For example, for meningococcus (meningococci), can classify according to the textural difference of its capsular polysaccharide.These capsular polysaccharides have different antigenicities, can determine five kinds of main serotypes (A, B, C, Y and W-135) thus.Enzyme linked immunosorbent assay (ELISA) or radioimmunoassay test (RIA) can be assessed this type of production of antibodies.These two kinds of methods can detect the specific antibody that host animal produces in course of infection.The shortcoming of these two kinds of methods is that host animal produces antibody and needs certain hour, and regular meeting misses the extremely early stage of infection thus.In addition, use this antibody-like can not distinguish previous infection and existing disease infection reliably.

Recently, the purposes of molecular method in the diagnose infections disease caused people's interest.These methods can be carried out responsive and special detection to microorganism.The example of these class methods comprises " branched DNA " signal detection system.This method is to use an example (Urdea MS et al.Branched DNA amplification multimers for the sensitive, the direct detection ofhuman HIV and hepatitis viruses.Nucleic Acids Symp Ser.1991 of sandwich hybridization principle; (24): 197-200).

Another method of Bacteria Detection and classification is an amplification 16S ribosome-RNA(rRNA) sequence.Reported that 16SrRNA is to use the suitable targets of pcr amplification test bacterial detection kind in various clinical or environmental samples, and, 16S rRNA gene is often used in the multiple special microorganism (Cloud of evaluation owing to having the special polymorphism of species, J.L., H.Neal, R.Rosenberry, C.Y.Turenne, M.Jama, D.R.Hillyard, and K.C.Carroll.2002.J.Clin.Microbiol.40:400-406).Yet, these class methods need the pure growth of bacterium, and after pcr amplification, still need to sample check order or with microarray type device hybridization to determine kind (the Fukushima M of bacterium, Kakinuma K, Hayashi H, Nagai H, Ito K, Kawaguchi R.J Clin Microbiol.2003 Jun; 41 (6): 2605-15).Therefore, the consuming time and consumption power of this class methods consumption wealth.

Though determined the genome of most microorganisms, obtained the specific probe or the primer that are used to detect target microorganism and still have any problem by sequential analysis.Because genome comprises four kinds of bases, what therefore very difficult usually preparation was enough has specific degenerated primer or probe to specified microorganisms.Another potential problem is by some important gene of the specified microorganisms of Granting of patent right or the genomic right to use.This right of ownership can stop or postpone competitive detection method and come into the market.The new nucleic acid that therefore, need can be used as the marker of specified microorganisms.

The present invention has obtained the modification of nucleic acids of multiple microorganism, and described modification of nucleic acids has the microorganism specificity, and can be used for detecting microorganism.

Summary of the invention

On the one hand, the invention provides derivative nucleic acids or the modification of nucleic acids of hepatitis C virus (Hepatitis C virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:76 in the sequence table 51, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of acinetobacter (Acinetobacter sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 1, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of bacillus (Bacillus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 2, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Bacteroides (Bacteroides sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 3, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Bartonella (Bartonella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 4, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Bordetella (Bordetella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 5, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Borrelia (Borrelia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 6, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Brucella (Brucella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 7, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Campylobacter (Campylobacter sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 8, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of chlamydiaceae (Chlamydia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 9, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of fusobacterium (Clostridium sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:39 in the sequence table 10, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of corynebacterium (Cornebacterium sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 11, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of intestinal bacteria (Escherichia coli), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 12, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or modification of nucleic acids that the Ai Like body belongs to (Ehrlichia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 13, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of enterococcus spp (Enterococcus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 14, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of fusobacterium (Fusobacterium sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 15, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of hemophilus (Haemophilus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 16, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of screw rod Pseudomonas (Helicobacter sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 17, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of legionella (Legionella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 18, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of leptospira (Leptospira sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 19, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of listeria (Listeria sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 20, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Mycobacterium (Mycobacterium sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 21, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Mycoplasma (Mycoplasma sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 22, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Neisseria (Neisseria sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 23, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Nocardia (Norcadia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 24, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Rhodopseudomonas (Pseudomonas sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 25, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Dermacentroxenus (Rickettsia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 26, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of salmonella (Salmonella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 27, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of serratia (Seratia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 28, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Shigella (Shigella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 29, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Staphylococcus (Staphylococcus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:52 in the sequence table 30, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of streptococcus (Streptococcus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 31, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of streptomyces (Streptomyces), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 32, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of treponema (Treponema), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 33, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Trophermya sp, its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 34, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of plasmodium (Plasmodium sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:60 in the sequence table 35, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Aspergillus (Aspergillis sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 36, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Candida (Candida sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:24 in the sequence table 37, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of genera cryptococcus (Cryptococcus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 38, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Paracoccidioides (Paracoccidioides sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 39, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Rhizopus (Rhizopus sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 40, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Mark Lewis-Francis Pseudomonas (Francisella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 41, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Vibrio (Vibrio sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 42, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of yersinia's genus (Yersinia sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 43, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of JC polyomavirus (JC polyomavirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 44, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Andean virus (Andes virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 46, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of hepatitis virus (hepatitis virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:24 in the sequence table 52, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides human immunodeficiency virus (Human Immunodeficiencyvirus, HIV) derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:128 in the sequence table 53, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of influenza virus (Influenza virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:162 in the sequence table 54, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of BK virus (BK virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 55, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Barmah virus (Barmah virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 56, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of tin pest poison in the card (Calcivirus virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 57, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of colorado tick fever virus (Colorado tick fever virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQID NO:48 in the sequence table 58, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of foot and mouth disease virus (Foot and Mouth virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:28 in the sequence table 59, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of GB Hepatitis virus (Hepatitis GB virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 60, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Heng Dela virus (Hendra virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 61, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human adenovirus (Human adenovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:24 in the sequence table 62, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human astrovirus virus (Human astrovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 63, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human bocavirus (Human bocavirus virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 64, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human coronary virus (Human coronavirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 65, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human intestine's virus (Human enterovirus virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 66, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of nerpes vinrus hominis (Human Herpes Virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:36 in the sequence table 67, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human metapneumovirus (Human metapneumovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 68, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human parainfluenza virus (Human parainfluenzavirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQID NO:12 in the sequence table 69, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of the lonely virus of human intestine (Human parechovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 70, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human rhinovirus (Human Rhinovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 71, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of human airway syncytial virus (Human respiratorysyncytial virus), its sequence is selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 72, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Measles virus (Measles virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 73, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of mumps virus (Mumps virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 74, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of norovirus (Norovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 75, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Norwalk virus (Norwalk virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 76, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of parvovirus (Parvovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 77, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of poliovirus (Poliovirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 78, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of rabies virus (Rabies virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 79, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of ross river virus (Ross River virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 80, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of rotavirus (Rotavirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:124 in the sequence table 81, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of sars coronavirus (SARS coronavirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 82, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of TT virus (TT virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 83, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of TTV microvirus (TTV minivirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 84, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of west nile virus (WestNile virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 85, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, (derivative nucleic acids or the modification of nucleic acids of α-virus), its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 86, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition to the invention provides alphavirus.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of camelpox virus (Camel pox virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 87, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of vaccinia virus (Cow pox virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 88, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or modification of nucleic acids that the Cox body belongs to (Coxiella sp), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 89, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of crimean-Congo hemorrhagic fever virus (Crimean-Congo HF), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQID NO:12 in the sequence table 90, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of dengue fever virus (Dengue virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 91, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Eastern equine encephalitis virus (Eastern Equine Encephalitisvirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 92, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Ebola virus (Ebola virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 93, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Marburg virus (Marburg virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 94, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of guanarito virus (Guanarito virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 95, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Hantaan virus (hanta virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 96, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of hantaan virus (Hantan virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 97, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of japanese encephalitis virus (Japanese encephalitis virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ IDNO:4 in the sequence table 97, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Junin virus (Junin virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 99, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of lassa virus (Lassa virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 100, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of machupo virus (Machupo virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 101, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of monkey pox virus (Monkey pox virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 102, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides the derivative nucleic acids or the modification of nucleic acids of the scorching virus of Lay valley head not (Murray Valley encephalitisvirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 103, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Nipah virus (Nipah virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 104, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Rift Valley fever virus (Rift Valley Fever virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 105, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Sabia's virus (Sabia virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 106, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Xin Nuobai C-type virus C (Sin Nombre virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 107, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of variola major virus (Variola major vruis), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 108, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of milk-pox virus (Variola minor virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 109, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Venezuelan equine encephalitis virus (Venezuelan equineencephalitis virus), its sequence is selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 110, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of Western equine encephalitis virus (Western equine encephalitisvirus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 111, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

On the other hand, the invention provides derivative nucleic acids or the modification of nucleic acids of yellow fever virus (Yellow Fever virus), its sequence is selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 112, comprises at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

The part of derivative nucleic acids or microbial nucleic acids can be at least 20,21,22,23,24,25,26,27,28,29,30,40,50,60,70,80,90,100 etc. Nucleotide or more Nucleotide.Some derive or microbial nucleic acids in, its part can for example be 15,16,17,18 or 19 Nucleotide less than 20 Nucleotide.

Can the reagent (for example hydrosulfate) that cytosine(Cyt) changes uridylic into be handled the derivative nucleic acids that microbial nucleic acids forms microorganism by utilization.After the derivative nucleic acids amplification, form the modified microorganism nucleic acid that has VITAMIN B4, guanine and thymine alkali bases basically.

For the double-stranded DNA that does not contain the cytosine(Cyt) that methylates usually, treatment step produces two kinds of derivative nucleic acids, and every kind all comprises VITAMIN B4, guanine, thymus pyrimidine and uridylic base.Two kinds of derivative nucleic acids originate from two strands in double-stranded DNA.Described two kinds of derivative nucleic acids do not contain cytosine(Cyt) substantially, but still have identical total alkali cardinal sum sequence length with the initial dna molecular that is untreated.Importantly, described two kinds of derivatives and be complimentary to one another and form cochain and following chain.Can use one or more chain to produce derivative nucleic acids or one or more chain that increases to produce modified nucleic acid molecule.

Unless article content has needs in addition, in this specification, term " comprises " (comprise, comprises, comprising) should be understood that to contain specified element, integral body or step, perhaps element set, integral body are organized or the step group, but do not get rid of other element, integral body or step, perhaps element set, whole group or step group yet.

Any discussion that comprises in this manual file (document), operation, material, device, article etc. all is only for the purpose that content of the present invention is provided.Can not think since above in each perhaps all the elements before the priority date of every claim of the application, exist in Australia, just assert that these contents form the basis of part prior aries or the general general knowledge of association area of the present invention.

In order more to be expressly understood the present invention, can do preferred embodiment is set forth with embodiment with reference to the following drawings.

The accompanying drawing summary

Fig. 1: genome (cochain) sequence (SEQ ID NO:77 in the sequence table 51) that shows hepatitis C virus 1a.

Fig. 2: genome (following chain) sequence (SEQ ID NO:78 in the sequence table 51) that shows hepatitis C virus 1a.

Fig. 3: the genome of deriving (cochain) sequence (SEQID NO:1 in the sequence table 51) that shows hepatitis C virus 1a.

Fig. 4: the genome of deriving (following chain) sequence (SEQID NO:20 in the sequence table 51) that shows hepatitis C virus 1a.

Fig. 5: modifying factor group (cochain) sequence (SEQID NO:39 in the sequence table 51) that shows hepatitis C virus 1a.

Fig. 6: modifying factor group (following chain) sequence (SEQID NO:58 in the sequence table 51) that shows hepatitis C virus 1a.

Embodiments of the present invention

Definition

Term as used herein " genomic modification " expression is modified to genome (or other) nucleic acid and comprises bases adenine (A), guanine (G), thymus pyrimidine (T) basically, but still have the form of essentially identical total alkali radix by the form that comprises VITAMIN B4 (A), guanine (G), thymus pyrimidine (T) and four bases of cytosine(Cyt) (C).

Term as used herein " derivative nucleic acids " expression comprises A, G, T and U base (or the base of some other non-A, G or T or base sample material) basically and has nucleic acid with the essentially identical total alkali radix of corresponding unmodified microbial nucleic acids.In using the process of agent treated, cytosine(Cyt)s all basically in the microbial DNA all are converted into uridylic.The variant (for example methylated cytosine(Cyt)) that is appreciated that cytosine(Cyt) may not be converted into uridylic (or the base of some other non-A, G or T or base sample material).Because microbial nucleic acids does not comprise the cytosine(Cyt) that methylates (or other cytosine(Cyt) variant) usually, so treatment step preferably transforms all cytosine(Cyt)s.Preferred cytosine(Cyt) is modified to uridylic.

The nucleic acid product of being obtained after term as used herein " modification of nucleic acids " the expression amplification derivative nucleic acids.In the process of amplification derivative nucleic acids, the uridylic in the derivative nucleic acids is replaced by thymus pyrimidine (T) to form modified nucleic acid molecule.The product that is produced has with corresponding unmodified microbial nucleic acids and has essentially identical total alkali radix, but is made up of the combination of three kinds of bases (A, G and T) basically.

Term as used herein " modification sequence " expression amplification derivative nucleic acids forms the nucleotide sequence that produces behind the modification of nucleic acids.The modification sequence that is produced has and the essentially identical total alkali radix of corresponding unmodified microbial nucleic acids sequence, but is made up of the combination of three kinds of bases (A, G and T) basically.

The nucleotide sequence of microbial nucleic acids before term as used herein " unconverted sequence " expression is handled.Unconverted sequence is the sequence of naturally occurring microbial nucleic acids normally.

Term as used herein " modification " expression cytosine(Cyt) is to the conversion of another kind of Nucleotide.Preferred reagent is modified into uridylic to form derivative nucleic acids with cytosine(Cyt).

Term as used herein " is modified the reagent of cytosine(Cyt) ", and expression can be converted into cytosine(Cyt) the reagent of another chemical substance.Preferably, reagent is converted into uridylic with cytosine(Cyt), replaces described uridylic by thymus pyrimidine subsequently in the amplification procedure of derivative nucleic acids.The reagent that is used to modify cytosine(Cyt) is preferably sodium bisulfite.Can also use in the method for the invention cytosine(Cyt) but other reagent that cytosine(Cyt) that methylates is not carried out similar modification.Example includes but not limited to hydrosulphite, acetate or Citrate trianion.Described reagent preferably can be modified into cytosine(Cyt) the sodium bisulfite of uridylic under the acidic aqueous solution condition.Sodium bisulfite (NaHSO ₃) easily with 5 of cytosine(Cyt), the two keys reactions of 6-are forming sulfonation cytosine(Cyt) reaction intermediates, and deamination easily takes place this intermediate, and under the situation that has water to exist generation uridylic sulphite.If necessary, can under weak basic condition, remove the sulphite group, thereby produce uridylic.Therefore, all cytosine(Cyt)s all may be converted into uridylic.Yet,, modify reagent and can not transform any cytosine(Cyt) that methylates owing to be subjected to methylated protection.Be appreciated that also and can modify cytosine(Cyt) (or other any base) to obtain the derivative nucleic acids that the present invention was instructed by the mode of enzymatic.

The genetics method of base mainly contains two kinds in the modification of nucleic acids, i.e. chemical process and enzymatic means.Therefore, modification of the present invention can also be implemented by naturally occurring enzyme, and perhaps the enzyme that obtains of artificial constructed enzyme or the screening by present report is implemented.Chemical treatment, for example the hydrosulphite method can be converted into uridylic with cytosine(Cyt) by suitable chemical step.Similarly, for example Isocytosine deaminase can be finished this conversion to form derivative nucleic acids.As far as we know, be 1932 about the reported first of Isocytosine deaminase, Schmidt, G., Z.physiol.Chem., 208,185; (in addition referring to 1950, Wang, TP., Sable, H.Z., Lampen, J.O., J.Biol.Chem, 184,17-28, Enzymatic deamination ofcytosines nucleosides).In this early stage work, can not obtain the Isocytosine deaminase that does not contain other nucleodeaminase, yet people such as Wang can be purified into from yeast or intestinal bacteria and have this type of active material.Therefore, any Enzymatic transformation (finally causing inserting the base that is different from cytosine(Cyt) in the site that Enzymatic transformation takes place in the reproduction process subsequently) for the cytosine(Cyt) that carries out for the formation derivative nucleic acids all can produce the modifying factor group.Successively produce the chemistry or the Enzymatic transformation of deriving with the modifying factor group and can be applied to any nuclear base (nucleo-base), no matter described nuclear base is natural purine or the pyrimidine that exists in the nucleic acid in the microorganism.

Term as used herein " modified forms of genome or nucleic acid " expression since by suitable chemically modified with subsequently amplification procedure with most of in the genome or all C change into T, thereby the natural existence that comprises four common bases G, A, T and C usually or synthetic genome or nucleic acid mainly only are made up of three kinds of bases G, A and C now.Genomic modified forms means that genomic relative complexity has reduced, and it is reduced to the composition of three bases from the composition based on four bases.

The material that forms is modified in term as used herein " base sample material " expression by cytosine(Cyt).In the amplification procedure of derivative nucleic acids, archaeal dna polymerase can be discerned base sample material, and described polysaccharase make A, G or T be distributed on the complementary dna chain of new formation with described derivative nucleic acids on the relative position of base sample material.Usually, base sample material is that the cytosine(Cyt) in the corresponding microbial nucleic acids that is untreated is modified the uridylic that obtains.The example of base sample material comprises any nuclear base, and no matter described nuclear base is purine or pyrimidine.

Term as used herein " relative complexity reduction " is relevant with probe length, promptly under given molecule condition, two genomes for identical size, the increase of required average probe length when reaching phase homospecificity and hybridization level at the probe of specific site, wherein first genome is " virgin state ", and by G, A, T and four kinds of based compositions of C, and second genome has identical length, but some of them cytosine(Cyt) (ideally being all cytosine(Cyt)s) has been converted into thymus pyrimidine.The site of detecting is positioned at identical position in the unconverted genome of primary and transforming gene group.On average, be in the normal gene group of 4,194,304 bases in length by G, A, T and four kinds of based compositions of C, have only a unique position accurately to hybridize (4 with the 11-mer probe ¹¹=4,194,304).Yet in a single day by the conversion of hydrosulphite or other appropriate method, the genome that is transformed is just only by three kinds of based compositions, and its complicacy significantly descends for the normal gene group of these type of 4,194,304 bases.Yet the result that this genome complicacy reduces no longer has the unique site that can hybridize mutually with the 11-mer probe of the above-mentioned uniqueness of this paper in the modifying factor group.And the result who carries out the hydrosulphite conversion is other possible sites of equal value that produced a lot of 11 base sequences separately.Therefore, the probe that just needs a 14-mer with seek original site and with its hybridization.Though as if this disagree with intuition at first, seem identical part (its have more multiclass like sequence) because have in the genome, so the length that people need prolong probe is to detect original site in the modifying factor group that comprises three kinds of bases at present more.Therefore, the reduction of genome relative complexity (in other words conj.or perhaps, comprising three kinds of simplification that base is such) means that the longer probe of needs design is to seek initial unique site.

Term as used herein " relatively genome complicacy reduce " can be by comparing with not modified DNA, and the length increase of desired microorganisms specific probe is calculated.This term is also contained and is measured whether microorganism exists and the type of the probe sequence that uses.These probes can have unconventional skeleton, the unconventional skeleton of PNA or LNA for example, perhaps as the unconventional skeleton of the modification skeleton additive (modified additions to a backbone) of in INA, setting forth.Therefore, it is irrelevant to think that genome has an added ingredients (for example described in the INA) whether the relative complexity of minimizing and probe have as imbedibility pseudonucleus thuja acid (Intercalatingpseudonucleotides).Example includes but not limited to, DNA, RNA, lock nucleic acid (LNA), peptide nucleic acid(PNA) (PNA), MNA, altritol nucleic acid (altritol nucleic acid, ANA), hexitol nucleic acid (HNA), imbedibility nucleic acid (INA), cyclohexyl nucleic acid (CNA) and composition thereof and its hybrid, with and the phosphorus atom modifier, such as but not limited to thiophosphatephosphorothioate, methyl phosphorodithioate, phosphoramidite, phosphorodithioate (phosphorodithiates), seleno phosphoric acid ester (phosphoroselenoates), phosphotriester and boryl phosphoric acid ester (phosphoboranates).The Nucleotide that non-natural exists includes but not limited to be contained in the Nucleotide in the and the following: DNA, RNA, PNA, INA, HNA, MNA, ANA, LNA, CNA, CeNA, TNA, (2 '-NH)-TNA, (3 '-NH)-TNA, α-L-ribo-LNA, α-L-wood sugar-LNA, β-D-wood sugar-LNA, α-D-ribo-LNA, [3.2.1]-LNA, dicyclo-DNA, 6-amino-dicyclo-DNA, 5-table-dicyclo-DNA, α-dicyclo-DNA, three ring-DNA, dicyclo [4.3.0]-DNA, dicyclo [3.2.1]-DNA, dicyclo [4.3.0] acid amides-DNA, β-D-ribopyranose base-NA, α-L-pyrans lysol glycosyl-NA, 2 '-R-RNA, α-L-RNA or α-D-RNA, β-D-RNA.In addition, can use and not wrap phosphorated compound connection Nucleotide, described compound is such as but not limited to the linking group of methyl-imino methyl, formacetate, thioformacetate and amide containing.Especially, nucleic acid and nucleic acid analog can comprise one or more imbedibility pseudonucleus thuja acids (IPN).The existence of IPN does not belong to the nucleic acid molecule complicacy and describes this part content, skeleton part (for example in PNA) that neither this complicacy.

" INA " expression according to WO 03/051901, WO 03/052132, WO 03/052133 and WO 03/052134 (Unest A/S) instruction imbedibility nucleic acid, more than incorporate this paper by reference into.INA is oligonucleotide or the oligonucleotide analogs that comprises one or more imbedibility pseudonucleus thuja acids (IPN) molecule.

The nucleic acid that " HNA " expression is set forth in nineteen ninety-five as people such as Van Aetschot.

The nucleic acid that " MNA " expression is set forth in 1998 as people such as Hossain.

" ANA " refers to the nucleic acid in elaboration in 1999 by people such as Allert.

" LNA " can be any LNA molecule that WO 99/14226 (Exiqon) sets forth, and LNA is preferably selected from the molecule of describing in WO 99/14226 summary.LNA is people such as the Singh nucleic acid that the people sets forth in 1997 in people such as 1998 or Obika in, Koshkin in 1998 etc. more preferably.

" PNA " refers to the peptide nucleic acid(PNA) in elaboration in 1991 as people such as Nielsen.

This paper employed " relative complexity reduction " does not relate to the order that base exists, the any mathematical complexity difference between the sequence A AAAAAATTTTTTT (SEQ ID NO :) of sequence A TATATATATATAT (SEQ ID NO :) and same length for example, the original associated data again (original re-association data) (and inferential genome complicacy) that does not also relate to relative genome size, wherein by Waring, M.﹠amp; Britten R.J.1966, Science, 154,791-794; And Britten, R.J andKohne D E., 1968, Science, 161,529-540 and wherein derive from Carnegie Institution ofWashington Yearbook early with reference to " original associated data again " is incorporated in the scientific literature.

" genome relative complexity " used herein is meant the not change position (original gene group and unconverted genome all have base in 1 to n constant position) of base in two genomes being estimated by molecular probe.For the monoploid human genome of specific human women's 3,000,000,000 base pairs, described constant position is defined as 1 to n, and wherein n is 3,000,000,000.If in 1 to n sequence, i base is C in the original gene group, and i base is T in the transforming gene group so.

Term used herein " genomic nucleic acids " comprises the nucleic acid of RNA, DNA, the coded protein of microorganism (prokaryotic micro-organisms and unicellular eukaryotic microorganisms), the not nucleic acid of coded protein and the ribosomal gene district of prokaryotic micro-organisms and unicellular eukaryotic microorganisms.

Karyomit(e), extrachromosomal nucleic acid contained in term used herein " microbial genome ", and this genomic interim component (for example plasmid, microorganism phage) and broadest movable material.Described " genome " has a core component as the S.galactiae example, also may have different different encoded and the uncoded components between the species of separating.

Term used herein " derived dna of microorganism " comprises directly the DNA that obtains from microorganism or microorganism RNA is changed into DNA and the DNA that obtains indirectly by any known or appropriate method (for example reverse transcription).

Term used herein " microorganism " comprises phage, virus, viroid, bacterium, fungi, algae, protozoon, spirobacteria, (in any case the classification of unicellular organism or any other microorganism, for example by the Kingdom Protoctista by Margulis, L., et al 1990, Handbook ofProtoctista, Jones and Bartlett, Publishers, Boston USA) or the microorganism relevant with the mankind (as Harrisons Principles of Internal Medicine, the 12nd edition, edited by J D Wilsonet al., McGraw Hill Inc, and the definition in the follow-up version).Also comprise set forth with OMIM (Online Mendelian Inheritance in Man, Www.ncbi.gov) all relevant microorganisms of the middle human disorders that defines.

The molecule that term used herein " microorganism specific nucleic acid molecule " expression utilizes method of the present invention to determine or obtain, have one or more microorganism specific sequences.

Term used herein " the taxonomy level of microorganism " comprises section, genus, kind, strain, type or from the different population of identical or different geography or deep-sea population.For bacterium, can use the conventional division bacteria figure (schema) that generally acknowledges, for example bacterium → bacteroid → β-bacteroid → Neisseria order → Neisseriaceae → eisseria.Because the variation of mononucleotide; perhaps be present in the change of the middle existence of dna molecular (for example plasmid or phagemid) in the microorganism with form in the cell; perhaps because may there be polymorphism in the polymorphism chromosomal region (as the bacterial virulence island) of microbial genome thereby make between different population.Microorganism and virus genomic flowability gain public acceptance, and it also comprises can be by the virus genomic chimeric character of individual core acid fragment embodiment.Therefore, can produce new bacterial strain by the genomic reprovision of different animals (re-assortment), for example new mankind influenza bacterial strain is from other Mammals or the segmental mosaic of birds viral genome gained.

Term used herein " close sequence similarity " comprise the definition of above-mentioned sequence relative complexity and with probe length as measurement standard.

Term " hybridize under stringent condition " can use with term " can hybridize under stringent condition " exchange, and expression can be differentiated nucleic acid simply by the ability of its microbial nucleic acids of modifying with all or part hybridization under stringent condition in this article.Can represent that the annealing of nucleic acid takes place down in standard conditions (for example high temperature and/or lower salt content) by hybridize under stringent condition, this conditions favouring is in the hybridization that prevents the incomplementarity nucleotide sequence.Maniatis, T., et al., Molecular Cloning:A Laboratory Manual, ColdSprings Harbor Laboratory, 1982, the example of having set forth the strict experimental program of nucleic acid probe and fixed dna hybridization in the 387-389 page or leaf (comprises 0.1 * SSC, 68 ℃ continue 2 hours), however can change experiment condition according to application.

Material and method

The extraction of DNA

Usually can obtain microbial DNA (or viral RNA) from any suitable source.Example includes but not limited to: cell culture, broth culture, environmental samples, clinical sample, body fluid, liquid sample, solid sample (for example tissue).Can from sample, obtain microbial DNA by standard method.It below is the example of suitable extracting method.Target sample is placed the 400 μ l solution that comprise 7M Guanidinium hydrochloride, 5mM EDTA, 100mM Tris/HCl (pH6.4), 1% Triton-X-100,50mM Proteinase K (Sigma), 100 μ g/ml yeast tRNA.Use the disposable pestle of 1.5ml to make the thorough homogenate of sample, and placed 48 hours at 60 ℃.After hatching, sample is carried out five freeze/melt circulation (dry ice 5 minutes/95 ℃ 5 minutes).Subsequently, sample is carried out vortex vibration (vortex) and in Eppendorf centrifuge centrifugal 2 minutes with the sedimentation cell fragment.Supernatant is moved in the clean test tube, and dilution is to reduce salt concn, and carry out phenol subsequently: chloroform extracting, ethanol sedimentation also are resuspended among the 50 μ l 10mM Tris/0.1mM EDTA.

Particularly, the method for extraction DNA is as follows Gram-positive on being grown in standard agar plate (having the nutritional needs that is specific to each bacterial classification) and the gram negative bacterium:

Below be the experimental program that from Gram-negative bacteria, extracts DNA:

A) use aseptic toothpick that bacterial colony is scraped the 1.5ml centrifuge tube from culture plate.

B) add 180 μ l guanidine thiocyanates and extract damping fluid (7M guanidine thiocyanate, 5mM EDTA (pH8.0), 40mM Tris/HCl (pH7.6), 1% Triton-X-100), mixing sample is with resuspended microbe colony.

C) add 20 μ l (20mg/ml) Proteinase Ks and make the sample thorough mixing.

D) hatch sample 3 hours with lysing cell at 55 ℃.

E) in each sample, add 200 μ l water also by soft piping and druming mixing sample.

F) add 400 μ l phenol/chloroforms/primary isoamyl alcohol (25:24:1), and vortex vibration sample twice, each 15 seconds.

G) subsequently with sample in Eppendorf centrifuge with 14, centrifugal 4 minutes of 000rpm.

H) water is moved in the clean centrifuge tube of 1.5ml.

I) add 400 μ l phenol/chloroforms/primary isoamyl alcohol (25:24:1), and vortex vibration sample twice, each 15 seconds.

J) subsequently with sample in Eppendorf centrifuge with 14, centrifugal 4 minutes of 000rpm.

K) water is moved in the clean centrifuge tube of 1.5ml.

L) ethanol of adding 800 μ l 100% in each sample, of short duration vortex vibration sample left standstill under-20 ℃ 1 hour subsequently.

M) under 4 ℃ with sample in Eppendorf centrifuge with 14, centrifugal 4 minutes of 000rpm.

N) precipitate with 500 μ l, 70% washing with alcohol DNA.

O) under 4 ℃ with sample in Eppendorf centrifuge with 14, centrifugal 5 minutes of 000rpm removes ethanol and will precipitate air-dry 5 minutes.

P) at last DNA is resuspended among 100 μ l 10mM Tris/HCl (pH8.0), the 1mM EDTA (pH8.0).

Q) by measure solution 230,260, the absorption value of 280nm calculates concentration and the purity of DNA.

The method of extracting DNA from gram positive bacterium is as follows:

A) use aseptic toothpick that bacterial colony is scraped the 1.5ml centrifuge tube from culture plate.

B) in each sample, add 180 μ l 20mg/ml N,O-Diacetylmuramidases (Sigma) and 200 μ g staphylococcus lysozymes (Sigma), and soft mixing sample is with resuspended bacterial colony.

C) sample is hatched 30 minutes with the degradation of cell wall at 37 ℃.

D) handle sample and basis subsequently and extract DNA at the method for the mini test kit of QIAamp DNA of gram positive bacterium.

From patient's cell sample, extract DNA:

A) acutely shake sample with resuspended any sedimentation cell and guarantee the homogeneity of solution with hand.

B) the 4ml re-suspended cell is transferred in the 15ml Costar centrifuge tube.

C) with described test tube in swing-out rotor (swing-out bucket rotor) centrifugal 15 minutes with 3000 * g.

D) incline carefully to and supernatant discarded and do not mix moving sedimentary cellular material.

E) sedimentary cell is resuspended in the 200 μ l lysis buffers (100mM Tris/HCl pH8.0,2mM EDTA pH8.0,0.5% SDS, 0.5% Triton-X-100) and is fully mixed to and obtain uniform solution.

F) 80 μ l samples being transferred to 96 hole samples prepares in the flat board.

G) add 20 μ l Proteinase Ks and solution hatched 1 hour (this process causes lysis) at 55 ℃.

From urine sample, extract DNA

According to QIAamp UltraSens ^TMThe virus handbook extracts DNA from initial volume is the urine of 1rml.The bisulf iotate-treated of dna sample

According to MethylEasy ^TMThe bisulphite modified test kit of high-throughput DNA (Human GeneticSignatures, Australia) carries out bisulf iotate-treated, also can vide infra.

Surprisingly, the inventor finds not need microbial DNA is separated (when for example having microbial DNA in human cell's sample) from the nucleic acid in other source.Treatment step can be used for the macro-mixing thing of different DNA types, and still can differentiate the microorganism specific nucleic acid by the present invention.According to estimates, the ultimate value that detects in the complex DNA mixture is the ultimate value of Standard PC R detection method, can be low to moderate the target nucleic acid molecule of a copy.

Sample

Any suitable sample may be used to the present invention.Example includes but not limited to microorganisms cultures, clinical sample, animal doctor's sample, biological liquid, tissue culture sample, environmental samples, water sample, effluent.Because the present invention is fit to detect any microorganism, therefore should not think that above tabulation is an exhaustive.

Test kit

Can implement the present invention in the mode of all ingredients box or composite reagent box, and specifically implement by manual, semi or fully automatic platform.In optimal way, can utilize automatization platform, by MethyEasy as EpMotion ^TMPerhaps high-throughput MethylEasy ^TMTest kit (Human GeneticSignatures Pty Ltd, Australia) transformed nucleic acid in 96 holes or 384 hole flat boards.

The processing of hydrosulphite

Below list sulphite and effectively handled the illustrative methods of nucleic acid.This method can keep all treated DNA substantially.This method is also referred to as human inheritance's mark (HGS) method in this article.The volume or the amount that should be understood that sample or reagent can change.

Can find the preferred method that is used for bisulf iotate-treated at US 10/428310 or PCT/AU2004/000549, the two all incorporates this paper by reference into.

Add the 3M NaOH (6g/50ml water, prepared fresh) of 2 μ l (1/10 volume) in 2 μ g DNA (can carry out predigestion with suitable Restriction Enzyme if desired), final volume is 20 μ l.Because hydrosulphite reagent preferably reacts with single chain molecule, so this step becomes single stranded form to the double chain DNA molecule sex change.This mixture was hatched 15 minutes at 37 ℃.Temperature more than room temperature is hatched the efficient that can be used to improve sex change.

After hatching, add 208 μ l 2M pyrosulphite hydrogen sodium (7.6g/20ml water and 416ml10N NaOH successively; BDH AnalaR #10356.4D; Prepared fresh) and 12 μ l 10mM Resorcinol (0.055g/50ml water, BDH AnalR #103122E; Prepared fresh).Resorcinol is a kind of reductive agent, and helps to reduce the oxidation of reagent.Also can use other reductive agent, for example dithiothreitol (DTT) (DTT), mercaptoethanol, quinone (quinhydrones) or other appropriate reductant.Cover sample with 200 μ l mineral oil.The covering of mineral oil can stop evaporation of reagents and oxidation, but optional.Subsequently with sample 55 ℃ of overnight incubation.Perhaps, make sample carry out following circulation in thermal cycler: to hatch as follows about 4 hours or spend the night: in the 1st step, 55 ℃ of circulations are 2 hours in the PCR instrument; The 2nd step, 95 ℃/2 minutes.The 1st step can carry out under any temperature between 37 ℃ to about 90 ℃, and the time can change between 5 minutes to 8 hours.The 2nd the step can under any temperature between about 70 ℃ to about 99 ℃, carry out, and the time can about 1 second to 60 minutes or longer between the variation.

After handling with pyrosulphite hydrogen sodium, remove mineral oil, and if DNA concentration low, then add 1 μ l tRNA (20mg/ml) or 2 μ l glycogens.These additives are chosen wantonly, and particularly when DNA exists with lower concentration, and described additive can improve the output of DNA by the co-precipitation of itself and target DNA.When the amount of nucleic acid during less than 0.5 μ g, need usually to use additive as carrier with precipitate nucleic acids more effectively.

Purify (cleanup) processing according to the following Virahol that carries out: in sample, add 800 μ l water, mix, add the 1ml Virahol subsequently.Water or damping fluid with the concentration of hydrosulphite in the reaction vessel be reduced to salt not with the level of target nucleic acid coprecipitation.It is about 1/4 to 1/1000 that extent of dilution is generally, as long as the concentration of salt is diluted to is lower than as desired extent disclosed herein.

Once more mixing sample and place 4 ℃ at least 5 minutes.Sample in Eppendorf centrifuge centrifugal 10-15 minute, and will precipitate ETOH washed twice with 70%, all carry out the vortex vibration at every turn.This carrying out washing treatment can be removed the residual salt with the nucleic acid coprecipitation.

To precipitate among the T/E (10mMTris/0.1mM EDTA) of the pH7.0-12.5 that is resuspended in suitable volumes (for example 50 μ l) after the drying.The damping fluid that has now found that pH10.5 is especially effective.According to the needs that nucleic acid suspends, sample was hatched 1 minute to 96 hours at 37 ℃ to 95 ℃.

Can find another example of bisulf iotate-treated in WO 2005021778 (incorporating this paper by reference into), this example provides and has made cytosine(Cyt) be converted into the method and the material of uridylic.In some embodiments, nucleic acid (for example gDNA) and hydrosulphite and polyamines catalyzer (for example triamine or tetramine) reaction.Randomly, described hydrosulphite comprises magnesium bisulfite.In other embodiments, choose wantonly in the presence of polyamines catalyzer and/or quaternary amine catalyzer, make nucleic acid and bisulfite reactive magnesium.The test kit that can be used for implementing the inventive method also is provided.Be appreciated that these methods all are suitable for the present invention in treatment step.

Amplification

In 25 μ l reaction mixtures (this mixture contains the genomic dna of 2 μ l through bisulf iotate-treated), use Promega PCR master mixture and primer (each primer 6ng/ μ l) to carry out pcr amplification.Use chain specificity nested primer to increase.Utilize PCR primer 1 and primer 4 to carry out the 1st and take turns pcr amplification (as follows).The 1st take turns pcr amplification after, 1 μ l amplification material transferred to comprise the 2nd of PCR primer 2 and primer 3 and take turns in the PCR premixture, and increase by aforementioned.The sample of PCR product is increased by following condition in ThermoHybaid PX2 thermal cycler: 95 ℃ 4 minutes, 1 circulation; Subsequently 95 ℃ 1 minute, 50 ℃ of 2 minutes and 72 ℃ 2 minutes, totally 30 circulations; 72 ℃ 10 minutes, 1 circulation.

Multiplex amplification

Need multiplex amplification if detect, can carry out following method.

1 μ l is added in the 25 μ l reaction systems that comprise following composition through the DNA of bisulf iotate-treated: x1 Qiagen multiplex master mixture, the 1st is taken turns INA or Oligonucleolide primers (each 5-100ng), 1.5-4.0mM MgSO ₄, dNTP (each 400uM) and 0.5-2 unit's polysaccharase mixture.Subsequently, described composition carries out following circulation in the thermal cycler of heat lid.Usually may have nearly 200 independent primer sequences in each amplified reaction.

The 1st step 94 ℃ of 1 circulations in 15 minutes

The 2nd the step 94 ℃ 1 minute

50 ℃ of 35 circulations in 3 minutes

68 ℃ 3 minutes

The 3rd step 68 ℃ of 1 circulations in 10 minutes

Subsequently 1 μ l the 1st is taken turns amplified production and transfer to the 2nd and take turns and carry out second in the reaction tube and take turns amplification, the wherein said the 2nd takes turns and contains enzyme reaction mixture and suitable second in the reaction tube and take turns primer.Circulate as mentioned above subsequently.

Primer

Any suitable PCR primer may be used to the present invention.Primer has and sequence complementary sequence to be amplified usually.Primer is oligonucleotide normally, but also can be oligonucleotide analogs.

Probe

Probe can be any suitable nucleic acid molecule or nucleic acid analog.Example include but not limited to DNA, RNA, lock nucleic acid (LNA), peptide nucleic acid(PNA) (PNA), MNA, altritol nucleic acid (ANA), hexitol nucleic acid (HNA), embedded nucleic acid (INA), cyclohexyl nucleic acid (CNA) and its mixture and its hybrid, with and the phosphorus atom modifier, such as but not limited to thiophosphatephosphorothioate, methyl phosphorodithioate, phosphoramidite, phosphorodithioate, seleno phosphoric acid ester, phosphotriester and boryl phosphoric acid ester.The Nucleotide that non-natural exists includes but not limited to be contained in the Nucleotide in the following material: DNA, RNA, PNA, INA, HNA, MNA, ANA, LNA, CNA, CeNA, TNA, (2 '-NH)-TNA, (3 '-NH)-TNA, α-L-ribo-LNA, α-L-wood sugar-LNA, β-D-wood sugar-LNA, α-D-ribo-LNA, [3.2.1]-LNA, dicyclo-DNA, 6-amino-dicyclo-DNA, 5-epi-dicyclo-DNA, α-dicyclo-DNA, three ring-DNA, dicyclo [4.3.0]-DNA, dicyclo [3.2.1]-DNA, dicyclo [4.3.0] acid amides-DNA, β-D-ribopyranose base-NA, α-L-pyrans lysol glycosyl-NA, 2 '-R-RNA, α-L-RNA or α-D-RNA, β-D-RNA.In addition, do not wrap the phosphorated compound and also can be used for connecting Nucleotide, this compound is such as but not limited to the linking group of methyl-imino methyl, formacetate, thioformacetate and amide containing.Particularly nucleic acid and nucleic acid analog can comprise one or more embedded pseudonucleus thuja acids.

Probe is preferably DNA or the DNA oligonucleotide that comprises one or more INA that formed by inner IPN.

Electrophoresis

According to E-gel system user guide ( Www.invitrogen.doc) carry out the electrophoresis of sample.

Detection method

Exist multiple possible detection system to measure the situation of expection sample.Should be appreciated that any known system or method that is used to detect nucleic acid molecule may be used to the present invention.Detection system includes but not limited to:

I. suitably the DNA of mark with can screen 10-the hybridization of the microarray type equipment of 200,000 one-components.This array can be formed by being positioned at any suitable solid phase (for example glass, plastics, mica, nylon, microballon, magnetic bead, fluorescent bead or film) lip-deep INA, PNA or Nucleotide or modified nucleotide array;

II.Southern hybridization type detection system;

III. Standard PC R detection system, sepharose for example, fluorescence reads for example genescan analysis.Sandwich hybridization detects, and the DNA staining reagent is ethidium bromide, Sybergreen for example, antibody test, and the ELISA flat board reads instrument type equipment, photofluorometer equipment;

IV. specific gene group amplified fragments or a plurality of genome amplification fragment or on it the variation PCR in real time quantitative;

The detection system of listing among the V.WO 2004/065625, for example fluorescent bead, enzyme conjugates, radioactivity pearl etc.;

VI. utilize as the amplification step of ligase chain reaction or as other detection system of the isothermal dna amplification technique of strand displacement amplification (SDA);

VII. multi-photon detection system;

VIII. gel electrophoresis and visual;

IX. be used for maybe may being used to detect the detection platform of nucleic acid.

Embedded nucleic acid

Embedded nucleic acid (INA) for non-natural exist can sequence-specific ground and nucleic acid (DNA and the RNA) polynucleotide of hybridizing.Because have multiple desirable character, so INA is based on the candidate of the cross experiment amplifying nucleic acid probe surrogate/substituent of probe.INA is a polymkeric substance, its with nucleic acid hybridization to form than naturally occurring corresponding nucleic/nucleic acid complex more stable hybrid on thermodynamics.They are not the substrates of enzyme of peptide or nucleic acid of degrading.Therefore, INA will be more stable in biological specimen, and compare with naturally occurring nucleic acid fragment and to have the longer shelf-life.Different with the nucleic acid hybridization that depends on very much ionic strength, the hybridization of INA and nucleic acid does not rely on ionic strength fully, and can be under the conditions of low ionic strength that is unfavorable for very much natural acid and nucleic acid hybridization and nucleic acid hybridization.The bonding strength of INA depends on by through engineering approaches and enters insertion group quantity in the molecule and the conventional interaction of hydrogen bond between the base of piling up in special mode in the duplex structure.DNA compares with DNA identification, and the recognition sequence of INA identification DNA is more effective.

Preferred INA is the phosphoramidite of (S)-1-O-(4,4 '-dimethoxytrityl methyl)-3-O-(1-pyrenyl methyl)-glycerine.

Synthesize INA by transformation to the standard oligonucleotide synthesis method of commercially available form.Can be at WO 03/051901, WO 03/052132, WO 03/052133 and WO 03/052134 (UnestA/S, belong to Human Genetic Signatures Pty Ltd, Australia) complete definition of discovery INA and synthetic in, it incorporates this paper by reference into.

Between the nucleic acid probe of INA probe and standard, there are many differences really.These differences can be divided into biological variability, textural difference and physical chemistry difference easily.As above hereinafter discussed, when attempting the INA probe is used for using the application of nucleic acid usually, these biological variabilities, textural difference and physical chemistry difference can produce the result that can not estimate.The non-equivalence of this different components can be observed in chemical field usually.

About biological variability, nucleic acid is as the material of heredity transmission and expression, and it is the biological substance that plays an important role in the life entity of living.The body internal characteristic of nucleic acid has obtained understanding quite fully.Yet INA is a kind of complete artificial molecule of developing recently, by chemist's design and by the synthetic preparation of organic chemistry.It does not also have known biological function.

INA is structurally also significantly different with nucleic acid.Though both can both use conventional nucleic acid base (A, C, G, T and U), the component of two molecules is structurally different.The skeleton of RNA, DNA and INA is made up of multiple ribose phosphodiester and 2-deoxyribosyl phosphodiester unit.It is one or more by link molecule and the big flat molecules of polymer phase bonded (large flat molecule) that the difference of INA and DNA or RNA is that it has.This flat molecules is embedded between the base of complementary dna chain relative with INA in the duplex structure.

The physical/chemical difference of INA and DNA or RNA also is significant.INA is faster than nucleic acid probe and identical target sequence bonded speed with complementary DNA bonded speed.Different with DNA or RNA fragment, unless insertion group is positioned at terminal position, otherwise INA seldom combines with RNA.Because the strong interaction between the base of insertion group and complementary dna chain, the stability of INA/DNA complex body will be higher than the stability of DNA/DNA or the similar complex body of RNA/DNA.

Different with other nucleic acid such as DNA or RNA fragment or PNA, INA does not have self aggregation or bonded character.

Because INA and nucleic acid hybridization have sequence-specific,, and be particularly suitable for test kit and screening detection so INA is the useful material standed for that is used to develop based on probe in detecting.Yet the INA probe is not the Equivalent of nucleic acid probe.Therefore, method, test kit or the composition that can improve specificity, sensitivity and confidence level based on probe in detecting all can be used for containing the detection, analysis of dna sample and quantitatively.INA has the necessary characteristic that realizes this purpose.

The result

In order to prove the present invention, Fig. 2 to 6 has shown the derivative nucleic acids of hepatitis C virus 1a or has simplified nucleic acid.Fig. 1 and Fig. 2 have shown the cochain and the following chain of the natural gene group of hepatitis C virus 1a respectively.Fig. 3 and Fig. 4 have shown that respectively all cytosine(Cyt)s in cochain and the following chain all have been replaced by the derivative nucleic acids of uridylic.Fig. 5 and Fig. 6 have shown modification of nucleic acids respectively, thus wherein in the derivative nucleic acids all uridylics all be replaced by the modification hepatitis C virus 1a nucleic acid that thymus pyrimidine forms cochain and following chain.

As can from Fig. 2 to 6, finding out, produced the new artificial gene group that four main can be used for detected or obtained suitable targets at hepatitis C virus 1a.Derivative nucleic acids and modification of nucleic acids are not naturally occurring, but can produce by bisulf iotate-treated (derivative nucleic acids) and amplification (modification of nucleic acids) usually.

Therefore the present invention is conceived to be obtained and had by naturally occurring microbial nucleic acids the novel nucleic acids of needed new purposes.

Derivative nucleic acids sequence of the microorganism of the present invention that provides in the appended sequence table (with the numerical order numbering) and the modification of nucleic acids sequence of microorganism have been provided table 1.Because the size and the sum of sequence are too huge, and its paper spare is not provided in the specification sheets of the present invention.Yet all sequences is incorporated this paper by reference into.

Table 1

Sequence microorganism sequence sequence

Show # number

1 acinetobacter acinetobacter calcoaceticus U ^*1

Acinetobacter calcoaceticus T ^*2

Acinetobacter calcoaceticus U RC ^*3

Acinetobacter calcoaceticus T RC ^*4

2 bacillus Bacillus anthraciss (Bacillus anthracis) U 1

Bacillus anthracis T 2

Bacillus anthracis U RC 3

Bacillus anthracis T RC 4

Bacillus cereus (Bacillus cereus) U 5

Bacillus cereus T 6

Bacillus cereus U RC 7

Bacillus cereus T RC 8

Subtilis (Bacillus subtilis) U 9

Subtilis T 10

Subtilis U RC 11

Subtilis T RC 12

3 Bacteroides bacteroides fragilises (Bacteriodes fragilis) U 1

Bacteroides fragilis T 2

Bacteroides fragilis U RC 3

Bacteroides fragilis T RC 4

4 Bartonella Chinese plug Bartonella (Bartonella henselae) U 1

Sequence microorganism sequence sequence

Show # number

Chinese plug Bartonella T 2

Chinese plug Bartonella U RC 3

Chinese plug Bartonella T RC 4

Trench fever Bartonella (Bartonella quintana) U 5

Trench fever Bartonella T 6

Trench fever Bartonella U RC 7

Trench fever Bartonella T RC 8

5 Bordetella Bordetella pertussis (Bordetella pertussis) U 1

Bordetella pertussis T 2

Bordetella pertussis U RC 3

Bordetella pertussis T RC 4

6 Borrelia Borrelia burgdoyferis (Borrelia burgdorferi) U 1

Borrelia burgdoyferi T 2

Borrelia burgdoyferi U RC 3

Borrelia burgdoyferi T RC 4

7 Brucella brucella melitensis belong to (Brucella melitensis) Chr1U 1

Brucella melitensis belongs to Chr1 T 2

Brucella melitensis belongs to Chr1 U RC 3

Brucella melitensis belongs to Chr1 T RC 4

Brucella melitensis belongs to Chr2 U 5

Brucella melitensis belongs to Chr2 T 6

Brucella melitensis belongs to Chr2 U RC 7

Brucella melitensis belongs to Chr2 T RC 8

8 Campylobacter campylobacter jejunis (Campylobacter jejuni) U 1

Campylobacter jejuni T 2

Campylobacter jejuni U RC 3

Campylobacter jejuni T RC 4

9 chlamydiaceae Chlamydia pneumoniae (Chlamydia pneumoniae) U 1

Sequence microorganism sequence sequence

Show # number

Chlamydia pneumoniae T 2

Chlamydia pneumoniae U RC 3

Chlamydia pneumoniae T RC 4

Chlamydia trachomatis (Chlamydia trachomatis) U 5

Chlamydia trachomatis T 6

Chlamydia trachomatis U RC 7

Chlamydia trachomatis T RC 8

10 fusobacterium Clostridium botulinums (Clostridium botulinum) toxin A U 1

Clostridium botulinum toxin A T 2

Clostridium botulinum toxin A U RC 3

Clostridium botulinum toxin A T RC 4

Clostridium botulinum toxin B U 5

Clostridium botulinum toxin B T 6

Clostridium botulinum toxin B U RC 7

Clostridium botulinum toxin B T RC 8

Clostridium botulinum toxin C U 9

Clostridium botulinum toxin C T 10

Clostridium botulinum toxin C U RC 11

Clostridium botulinum toxin C T RC 12

Clostridium botulinum toxin D U 13

Clostridium botulinum toxin D T 14

Clostridium botulinum toxin D U RC 15

Clostridium botulinum toxin D T RC 16

Clostridium botulinum toxin E U 17

Clostridium botulinum toxin E T 18

Clostridium botulinum toxin E F RC 19

Clostridium botulinum toxin E T RC 20

Clostridium botulinum toxin F U 21

Sequence microorganism sequence sequence

Show # number

Clostridium botulinum toxin F T 22

Clostridium botulinum toxin F U RC 23

Clostridium botulinum toxin F T RC 24

Clostridium difficile (Clostridium dififcile) U 25

Clostridium difficile T 26

Clostridium difficile U RC 27

Clostridium difficile T RC 28

Clostridium perfringens (Clostridium perfringens) U 29

Clostridium perfringens T 30

Clostridium perfringens U RC 31

Clostridium perfringens T RC 32

Clostridium tetani (Clostridium tetani) U 33

Clostridium tetani T 34

Clostridium tetani U RC 35

Clostridium tetani T RC 36

Clostridium botulinum U 37

Clostridium botulinum T 38

Clostridium botulinum U RC 39

Clostridium botulinum T RC 40

11 corynebacterium diphtheria corynebacteriums (Corynebacterium diptheriae) 1

U

Diphtheria corynebacterium T 2

Diphtheria corynebacterium U RC 3

Diphtheria corynebacterium T RC 4

C. jeikeium (Corynebacterium jeikeium) U 5

C. jeikeium T 6

C. jeikeium U RC 7

C. jeikeium T RC 8

Sequence microorganism sequence sequence

Show # number

12 esherichia coli U 1

Intestinal bacteria T 2

Intestinal bacteria U RC 3

Intestinal bacteria T RC 4

13 dust Garrick bodies belong to looks into ehrlichia chaffeensis body (Ehrlichia chaffeensis) U 1

Look into ehrlichia chaffeensis body T 2

Look into ehrlichia chaffeensis body U RC 3

Look into ehrlichia chaffeensis body T RC 4

14 enterococcus spp enterococcus faecalis (Enterococcus faecalis) U 1

Enterococcus faecalis T 2

Enterococcus faecalis U RC 3

Enterococcus faecalis T RC 4

15 fusiform bacilarmature accessories nuclear fusiform bacilarmature (Fusobacterium nucleatum) U 1

Tool nuclear fusiform bacilarmature T 2

Tool nuclear fusiform bacilarmature U RC 3

Tool nuclear fusiform bacilarmature T RC 4

16 hemophilus haemophilus ducreyis (Haemophilus ducreyi) U 1

Haemophilus ducreyi T 2

Haemophilus ducreyi U RC 3

Haemophilus ducreyi T RC 4

Hemophilus influenzae U 5

Hemophilus influenzae T 6

Hemophilus influenzae U RC 7

Hemophilus influenzae T RC 8

17 screw rod Pseudomonas Hp (Helicobacter pylori) U 1

Hp T 2

Hp U RC 3

Hp T RC 4

Sequence microorganism sequence sequence

Show # number

18 legionella legionella pneumophilias (Legionella pneumophila) U 1

Legionella pneumophilia T 2

Legionella pneumophilia U RC 3

Legionella pneumophilia T RC 4

19 leptospira question mark shape Leptospira (Leptospira interrogans) 1

Chr?I?U

Question mark shape Leptospira Chr I T 2

Question mark shape Leptospira Chr I U RC 3

Question mark shape Leptospira Chr I T RC 4

Question mark shape Leptospira Chr II U 5

Question mark shape Leptospira Chr II T 6

Question mark shape Leptospira Chr II U RC 7

Question mark shape Leptospira Chr II T RC 8

(Listeria 1 for 20 listeria listeria monocytogenes

monocytogenes)U

Listeria monocytogenes T 2

Listeria monocytogenes U RC 3

Listeria monocytogenes T RC 4

21 Mycobacterium mycobacterium aviums (Mycobacterium avium) U 1

Mycobacterium avium T 2

Mycobacterium avium U RC 3

Mycobacterium avium T RC 4

Mycobacterium leprae (Mycobacterium leprae) U 5

Mycobacterium leprae T 6

Mycobacterium leprae U RC 7

Mycobacterium leprae T RC 8

Mycobacterium tuberculosis (Mycobacterium tuberculosis) 9

U

Sequence microorganism sequence sequence

Show # number

Mycobacterium tuberculosis T 10

Mycobacterium tuberculosis U RC 11

Mycobacterium tuberculosis T RC 12

22 Mycoplasma mycoplasma pneumoniae (Mycoplasmapneumoniae) U 1

Mycoplasma pneumoniae T 2

Mycoplasma pneumoniae U RC 3

Mycoplasma pneumoniae T RC 4

23 Neisseria Diplococcus gonorrhoeaes (Neisseria gonorrhoeae) U 1

Diplococcus gonorrhoeae T 2

Diplococcus gonorrhoeae U RC 3

Diplococcus gonorrhoeae T RC 4

Neisseria meningitidis (Neisseria meningitides) 5

Serotype A U

Neisseria meningitidis serotype A T 6

Neisseria meningitidis serotype A U RC 7

Neisseria meningitidis serotype A T RC 8

Neisseria meningitidis serotypes B U 9

Neisseria meningitidis serotypes B T 10

Neisseria meningitidis serotypes B U RC 11

Neisseria meningitidis serotypes B T RC 12

24 Nocardia nocardia farcinicas (Nocardia farcinica) U 1

Nocardia farcinica T 2

Nocardia farcinica U RC 3

Nocardia farcinica T RC 4

25 Rhodopseudomonas Pseudomonas aeruginosas (Pseudomonas aeruginosa) U 1

Pseudomonas aeruginosa T 2

Pseudomonas aeruginosa U RC 3

Pseudomonas aeruginosa T RC 4

Sequence microorganism sequence sequence

Show # number

26 Dermacentroxenus Rickettsia prowazekiis (Rickettsia prowazekii) U 1

Rickettsia prowazekii T 2

Rickettsia prowazekii U RC 3

Rickettsia prowazekii T RC 4

Rickettsia typhi (Rickettsia typhi) U 5

Rickettsia typhi T 6

Rickettsia typhi U RC 7

Rickettsia typhi T RC 8

Kang Shi Rickettsiae (Rickettsia conorii) U 9

Kang Shi Rickettsiae T 10

Kang Shi Rickettsiae U RC 11

Kang Shi Rickettsiae T RC 1227 salmonella enteron aisle Salmonellas (Salmonella enterica) U 1

Enteron aisle Salmonellas T 2

Enteron aisle Salmonellas U RC 3

Enteron aisle Salmonellas T RC 4

(Salmonella 5 for mouse typhus enteron aisle Salmonellas

typhimurium)U

Mouse typhus enteron aisle Salmonellas T 6

Mouse typhus enteron aisle Salmonellas U RC 7

Mouse typhus enteron aisle Salmonellas T RC 8

28 serratia serratia marcescens (Serratia marscesens) U 1

Serratia marcescens T 2

Serratia marcescens U RC 3

Serratia marcescens T RC 4

29 Shigella shigella flexneris (Shigella flexneri) U 1

Shigella flexneri T 2

Shigella flexneri U RC 3

Sequence microorganism sequence sequence

Show # number

Shigella flexneri T RC 4

Shigella bogdii (Shigella boydii) U 5

Shigella bogdii T 6

Shigella bogdii U RC 7

Shigella bogdii T RC 8

Shigella dysenteriae (Shigella dysenteriae) U 9

Shigella dysenteriae T 10

Shigella dysenteriae U RC 11

Shigella dysenteriae T RC 12

30 Staphylococcus streptococcus aureuses (Staphylococcus aureus) U 1

Streptococcus aureus T 2

Streptococcus aureus U RC 3

Streptococcus aureus T RC 4

Staphylococcus epidermidis (Staphylococcus epidermidis) 5

U

Staphylococcus epidermidis T 6

Staphylococcus epidermidis U RC 7

Staphylococcus epidermidis T RC 8

Staphylococcus haemolyticus (Staphylococcus haemolyticus) 9

U

Staphylococcus haemolyticus T 10

Staphylococcus haemolyticus U RC 11

Staphylococcus haemolyticus T RC 12

Staphylococcal enterotoxin A U 13

Staphylococcal enterotoxin A T 14

Staphylococcal enterotoxin A U RC 15

Staphylococcal enterotoxin A T RC 16

Staphylococcal enterotoxin B U 17

Sequence microorganism sequence sequence

Show # number

Staphylococcal enterotoxin B T 18

Staphylococcal enterotoxin A B RC 19

Staphylococcal enterotoxin A B RC 20

Staphyloentero-toxin C U 21

Staphyloentero-toxin C T 22

Staphyloentero-toxin C U RC 23

Staphyloentero-toxin C T RC 24

Staphyloentero-toxin C1 U 25

Staphyloentero-toxin C1 T 26

Staphyloentero-toxin C1 U RC 27

Staphyloentero-toxin C1 T RC 28

Staphyloentero-toxin C3 U 29

Staphyloentero-toxin C3 T 30

Staphyloentero-toxin C3 U RC 31

Staphyloentero-toxin C3 T RC 32

Staphylococcal enterotoxin D U 33

Staphylococcal enterotoxin D T 34

Staphylococcal enterotoxin D U RC 35

Staphylococcal enterotoxin D T RC 36

Aureus enterotoxin E U 37

Aureus enterotoxin E T 38

Aureus enterotoxin E U RC 39

Aureus enterotoxin E T RC 40

Aureus enterotoxin G U 41

Aureus enterotoxin G T 42

Aureus enterotoxin G U RC 43

Aureus enterotoxin G T RC 44

Staphyloentero-toxin H U 45

Sequence microorganism sequence sequence

Show # number

Staphyloentero-toxin H T 46

Staphyloentero-toxin H U RC 47

Staphyloentero-toxin H T RC 48

Pu TaoqiujunchangdusuJ ﹠amp; R U 49

Pu TaoqiujunchangdusuJ ﹠amp; R T 50

Pu TaoqiujunchangdusuJ ﹠amp; RU RC 51

Pu TaoqiujunchangdusuJ ﹠amp; R T RC 52

31 streptococcus streptococcus agalactiaes (Streptococcus agalactiae) U 1

Streptococcus agalactiae T 2

Streptococcus agalactiae U RC 3

Streptococcus agalactiae T RC 4

Streptococcus mutans (Streptococcus mutans) U 5

Streptococcus mutans T 6

Streptococcus mutans U RC 7

Streptococcus mutans T RC 8

Streptococcus pneumoniae (Streptococcus pneumoniae) U 9

Streptococcus pneumoniae T 10

Streptococcus pneumoniae U RC 11

Streptococcus pneumoniae T RC 12

Micrococcus scarlatinae (Streptococcus pyrogene) U 13

Micrococcus scarlatinae T 14

Micrococcus scarlatinae U RC 15

Micrococcus scarlatinae T RC 16

32 streptomyces streptomyces coelicolors (Streptomyces coelicolor) U 1

Streptomyces coelicolor T 2

Streptomyces coelicolor U RC 3

Streptomyces coelicolor T RC 4

33 treponema Tyreponema pallidums (Treponema pallidum) U 1

Sequence microorganism sequence sequence

Show # number

Tyreponema pallidum T 2

Tyreponema pallidum U RC 3

Tyreponema pallidum T RC 4

34 Tropheryma belong to Tropheryma whippelii U 1

Tropheryma?whippelii?T 2

Tropheryma?whippelii?U?RC 3

Tropheryma?whippelii?T?RC 4

35 plasmodium plasmodium falciparums (Plasmodium falciparum) plastosome 1

U

Plasmodium falciparum plastosome T 2

Plasmodium falciparum plastosome U RC 3

Plasmodium falciparum plastosome T RC 4

Plasmodium falciparum Chr1 U 5

Plasmodium falciparum Chr1 T 6

Plasmodium falciparum Chr1 U RC 7

Plasmodium falciparum Chr1 T RC 8

Plasmodium falciparum Chr2 U 9

Plasmodium falciparum Chr2 T 10

Plasmodium falciparum Chr2 U RC 11

Plasmodium falciparum Chr2 T RC 12

Plasmodium falciparum Chr3 U 13

Plasmodium falciparum Chr3 T 14

Plasmodium falciparum Chr3 U RC 15

Plasmodium falciparum Chr3 T RC 16

Plasmodium falciparum Chr4 U 17

Plasmodium falciparum Chr4 T 18

Plasmodium falciparum Chr4 U RC 19

Plasmodium falciparum Chr4 T RC 20

Sequence microorganism sequence sequence

Show # number

Plasmodium falciparum Chr5 U 21

Plasmodium falciparum Chr5 T 22

Plasmodium falciparum Chr5 U RC 23

Plasmodium falciparum Chr5 T RC 24

Plasmodium falciparum Chr6 U 25

Plasmodium falciparum Chr6 T 26

Plasmodium falciparum Chr6 U RC 27

Plasmodium falciparum Chr6 T RC 28

Plasmodium falciparum Chr7 U 29

Plasmodium falciparum Chr7 T 30

Plasmodium falciparum Chr7 U RC 31

Plasmodium falciparum Chr7 T RC 32

Plasmodium falciparum Chr8 U 33

Plasmodium falciparum Chr8 T 34

Plasmodium falciparum Chr8 U RC 35

Plasmodium falciparum Chr8 T RC 36

Plasmodium falciparum Chr9 U 37

Plasmodium falciparum Chr9 T 38

Plasmodium falciparum Chr9 U RC 39

Plasmodium falciparum Chr9 T RC 40

Plasmodium falciparum Chr10 U 41

Plasmodium falciparum Chr10 T 42

Plasmodium falciparum Chr10 U RC 43

Plasmodium falciparum Chr10 T RC 44

Plasmodium falciparum Chr11 U 45

Plasmodium falciparum Chr11 T 46

Plasmodium falciparum Chr11 U RC 47

Plasmodium falciparum Chr11 T RC 48

Sequence microorganism sequence sequence

Show # number

Plasmodium falciparum Chr12 U 49

Plasmodium falciparum Chr12 T 50

Plasmodium falciparum Chr12 U RC 51

Plasmodium falciparum Chr12 T RC 52

Plasmodium falciparum Chr13 U 53

Plasmodium falciparum Chr13 T 54

Plasmodium falciparum Chr13 U RC 55

Plasmodium falciparum Chr13 T RC 56

Plasmodium falciparum Chr14 U 57

Plasmodium falciparum Chr14 T 58

Plasmodium falciparum Chr14 U RC 59

Plasmodium falciparum Chr14 T RC 60

36 Aspergillus aspergillus nigers belong to (Aspergillus niger) plastosome U 1

(Aspergillus) aspergillus niger plastosome T 2

Aspergillus niger plastosome U RC 3

Aspergillus niger plastosome T RC 4

Tabin aspergillus (Aspergillus tubingensis) plastosome U 5

Tabin aspergillus plastosome T 6

Tabin aspergillus plastosome U RC 7

Tabin aspergillus plastosome T RC 8

37 Candida Candida albicanss (Candida albicans) plastosome U 1

Candida albicans plastosome T 2

Candida albicans plastosome U RC 3

Candida albicans plastosome T RC 4

Candida glabrata (Candida glabrate) plastosome U 5

Candida glabrata plastosome T 6

Candida glabrata plastosome U RC 7

Candida glabrata plastosome T RC 8

Sequence microorganism sequence sequence

Show # number

Candida metapsilosis plastosome U 9

Candida metapsilosis plastosome T 10

Candida metapsilosis plastosome U RC 11

Candida metapsilosis plastosome T RC 12

Candida orthopsilosis plastosome U 13

Candida orthopsilosis plastosome T 14

Candida orthopsilosis plastosome U RC 15

Candida orthopsilosis plastosome T RC 16

Candida parapsilosis (Candida parapsilosis) plastosome 17

U

Candida parapsilosis plastosome T 18

Candida parapsilosis plastosome U RC 19

Candida parapsilosis plastosome T RC 20

Candida stellata plastosome U 21

Candida stellata plastosome T 22

Candida stellata plastosome U RC 23

Candida stellata plastosome T RC 24

38 genera cryptococcus Cryptococcus neoformans (Cryptococcus neoformans) var U 1

Cryptococcus neoformans var T 2

Cryptococcus neoformans var U RC 3

Cryptococcus neoformans var T RC 4

(Paracoccidioides 1 for 39 Paracoccidioides Paracoccidioides brasiliensises

Brasiliensis) plastosome U 2

Paracoccidioides brasiliensis plastosome T 3

Paracoccidioides brasiliensis plastosome U RC 4

Paracoccidioides brasiliensis plastosome T RC

40 Rhizopus Rhizopus oryzaes (Rhizopus oryzae) plastosome U 1

Rhizopus oryzae plastosome T 2

Sequence microorganism sequence sequence

Show # number

Rhizopus oryzae plastosome U RC 3

Rhizopus oryzae plastosome T RC 4

41 Francisella genus francisella Francisella (Francisella tularensis) U 1

Francisella tularensis T 2

Francisella tularensis U RC 3

Francisella tularensis T RC 4

42 Vibrio vibrio cholerae (Vibrio cholerae) karyomit(e) II U 1

Vibrio cholerae karyomit(e) II T 2

Vibrio cholerae karyomit(e) II U RC 3

Vibrio cholerae karyomit(e) II T RC 4

43 yersinia's genus yersinia pestis (Yersinia pestis) U 1

Yersinia pestis T 2

Yersinia pestis U RC 3

Yersinia pestis T RC 4

44 JC polyomavirus JC polyomavirus U 1

JC polyomavirus T 2

JC polyomavirus U RC 3

JC polyomavirus T RC 4

45 1

2

3

4

The big fragment U 1 of virus Andean, 46 Andeans virus

The big fragment T 2 of Andean virus

The big fragment U RC 3 of Andean virus

The big fragment T RC 4 of Andean virus

Fragment U 5 in the virus of Andean

Fragment T 6 in the virus of Andean

Sequence microorganism sequence sequence

Show # number

Fragment U RC 7 in the virus of Andean

Fragment T RC 8 in the virus of Andean

Andean virus small segment U 9

Andean virus small segment T 10

Andean virus small segment U RC 11

Andean virus small segment T RC 12

51 hepatitis C virus hepatitis C virus 1aT 1

Hepatitis C virus 2b T 2

Hepatitis C virus 1b/2k T 3

Hepatitis C virus 1c T 4

Hepatitis C virus 2a T 5

Hepatitis C virus 2b T 6

Hepatitis C virus 2C T 7

Hepatitis C virus 2K T 8

Hepatitis C virus 3a T 9

Hepatitis C virus 3B T 10

Hepatitis C virus 3k T 11

Hepatitis C virus 4a T 12

Hepatitis C virus 5a T 13

Hepatitis C virus 6a T 14

Hepatitis C virus 6b T 15

Hepatitis C virus 6g T 16

Hepatitis C virus 6d T 17

Hepatitis C virus 6h T 18

Hepatitis C virus 6k T 19

Hepatitis C virus 1a T RC 20

Hepatitis C virus 2b T RC 21

Sequence microorganism sequence sequence

Show # number

Hepatitis C virus 1b/2k T RC 22

Hepatitis C virus 1c T RC 23

Hepatitis C virus 2a T RC 24

Hepatitis C virus 2b T RC 25

Hepatitis C virus 2C T RC 26

Hepatitis C virus 2K T RC 27

Hepatitis C virus 3a T RC 28

Hepatitis C virus 3B T RC 29

Hepatitis C virus 3k T RC 30

Hepatitis C virus 4a T RC 31

Hepatitis C virus 5a T RC 32

Hepatitis C virus 6a T RC 33

Hepatitis C virus 6b T RC 34

Hepatitis C virus 6g T RC 35

Hepatitis C virus 6d T RC 39

Hepatitis C virus 6h T RC 37

Hepatitis C virus 6k T RC 38

Hepatitis C virus 1a U 39

Hepatitis C virus 2b U 40

Hepatitis C virus 1b/2k U 41

Hepatitis C virus 1c U 42

Hepatitis C virus 2a U 43

Hepatitis C virus 2b U 44

Hepatitis C virus 2C U 45

Hepatitis C virus 2K U 46

Hepatitis C virus 3a U 47

Hepatitis C virus 3B U 48

Hepatitis C virus 3k U 49

Sequence microorganism sequence sequence

Show # number

Hepatitis C virus 4a U 50

Hepatitis C virus 5a U 51

Hepatitis C virus 6a U 52

Hepatitis C virus 6b U 53

Hepatitis C virus 6g U 54

Hepatitis C virus 6d U 55

Hepatitis C virus 6h U 56

Hepatitis C virus 6k U 57

Hepatitis C virus 1a U RC 58

Hepatitis C virus 2b U RC 59

Hepatitis C virus 1b/2k U RC 60

Hepatitis C virus 1c U RC 61

Hepatitis C virus 2a U RC 62

Hepatitis C virus 2b U RC 63

Hepatitis C virus 2C U RC 64

Hepatitis C virus 2K U RC 65

Hepatitis C virus 3a U RC 66

Hepatitis C virus 3B U RC 67

Hepatitis C virus 3k U RC 68

Hepatitis C virus 4a U RC 69

Hepatitis C virus 5a U RC 70

Hepatitis C virus 6a U RC 71

Hepatitis C virus 6b U RC 72

Hepatitis C virus 6g U RC 73

Hepatitis C virus 6d U RC 74

Hepatitis C virus 6h U RC 75

Hepatitis C virus 6k U RC 76

Hepatitis C virus 1a genome T 77

Sequence microorganism sequence sequence

Show # number

Hepatitis C virus 1a genome UC 78

52 hepatitis virus hepatitis A (Hepatitis A) virus 1

Hepatitis B (Hepatitis B) virus 2

Hepatitis D (Hepatitis D) virus 3

Hepatitis E (Hepatitis E) virus-4

GA type hepatitis (Hepatitis GA) virus 5

GB type hepatitis (Hepatitis GB) virus 6

Hepatitis A virus RC 7

Hepatitis B virus RC 8

Hepatitis D virus RC 9

Hepatitis E virus RC 10

GA Hepatitis virus RC 11

GB Hepatitis virus RC 12

Hepatitis A virus U 13

Hepatitis B virus U 14

Hepatitis D virus U 15

Hepatitis E virus U 16

GA Hepatitis virus U 17

GB Hepatitis virus U 18

Hepatitis A virus U RC 19

Hepatitis B virus U RC 20

Hepatitis D virus U RC 21

Hepatitis E virus U RC 22

GA Hepatitis virus U RC 23

GB Hepatitis virus U RC 24

53 human immune deficiency HIV-1 Gp MA1 hypotypes 1

Virus (HIV) HIV-1 Gp MA2 hypotype 2

HIV-1 Gp MB hypotype 3

Sequence microorganism sequence sequence

Show # number

HIV-1 Gp M C hypotype 4

HIV-1 Gp M D hypotype 5

HIV-1 Gp M F1 hypotype 6

HIV-1 Gp M F2 hypotype 7

HIV-1 Gp M G hypotype 8

HIV-1 Gp M H hypotype 9

HIV-1 Gp M J hypotype 10

HIV-1 Gp M K hypotype 11

HIV-1?Gp?M?CRFA/E 12

HIV-1?Gp?M?A/G 13

HIV-1?Gp?M?A/B 14

HIV-1?Gp?M?A/G/I 15

HIV-1?Gp?M?F/D 16

HIV-1?Gp?M?A/G/J 17

HIV-1?Gp?M?C/B 18

HIV-1?Gp?M?B/C 19

HIV-1?Gp?M?A/F/G 20

HIV-1?Gp?M?C/D 21

HIV-1?Gp?M?A/E/J/G 22

HIV-1?Gp?M?B/F 23

HIV-1?Gp?M?A，CRF01AE 24

HIV-1?Gp?M?B/G 25

HIV-1?Gp?M?CRF01AE/B 26

HIV-1?Gp?M?A2/D 27

HIV-1?Gp?M?A，F，G，H，J 28

HIV-1?Gp?M?A/D/G 29

HIV-1?Gp?N 30

HIV-1?GpO 31

Sequence microorganism sequence sequence

Show # number

HIV-2 32

HIV-1 Gp M A1 blood subgroup RC 33

HIV-1 Gp M A2 blood subgroup RC 34

HIV-1 Gp M B hypotype RC 35

HIV-1 Gp M C hypotype RC 36

HIV-1 Gp M D hypotype RC 37

HIV-1 Gp M F1 hypotype RC 38

HIV-1 Gp M F2 hypotype RC 39

HIV-1 Gp M G hypotype RC 40

HIV-1 Gp M H hypotype RC 41

HIV-1 Gp M J hypotype RC 42

HIV-1 Gp M K hypotype RC 43

HIV-1?Gp?M?CRFA/E?RC 44

HIV-1?Gp?MA/G?RC 45

HIV-1?Gp?MA/B?RC 46

HIV-1?GpMA/G/I?RC 47

HIV-1?Gp?M?F/D?RC 48

HIV-1?Gp?MA/G/J?RC 49

HIV-1?Gp?M?C/B?RC 50

HIV-1?Gp?M?B/C?RC 51

HIV-1?Gp?MA/F/G?RC 52

HIV-1?Gp?M?C/D?RC 53

HIV-1?Gp?MA/E/J/G?RC 54

HIV-1?Gp?M?B/F?RC 55

HIV-1?Gp?M?A，CRF01AE?RC 56

HIV-1?Gp?M?B/G?RC 57

HIV-1?Gp?M?CRF01AE/B?RC 58

HIV-1?Gp?M?A2/D?RC 59

Sequence microorganism sequence sequence

Show # number

HIV-1?Gp?MA，F，G，H，J?RC 60

HIV-1?Gp?MA/D/G?RC 61

HIV-1?GpN?RC 62

HIV-1?Gp?O?RC 63

HIV-2?RC 64

HIV-1 Gp M A1 blood subgroup U 65

HIV-1 Gp M A2 blood subgroup U 66

HIV-1 Gp M B hypotype U 67

HIV-1 Gp M C hypotype U 68

HIV-1 Gp M D hypotype U 69

HIV-1 Gp M F1 hypotype U 70

HIV-1 Gp M F2 hypotype U 71

HIV-1 Gp M G hypotype U 72

HIV-1 Gp M H hypotype U 73

HIV-1 Gp M J hypotype U 74

HIV-1 Gp M K hypotype U 75

HIV-1?Gp?M?CRFA/E?U 76

HIV-1?Gp?M?A/G?U 77

HIV-1?Gp?M?A/B?U 78

HIV-1?Gp?M?A/G/I?U 79

HIV-1?Gp?M?F/D?U 80

HIV-1?Gp?M?A/G/J?U 81

HIV-1?Gp?M?C/B?U 82

HIV-1?Gp?M?B/C?U 83

HIV-1?Gp?M?A/F/G?U 84

HIV-1?Gp?M?C/D?U 85

HIV-1?Gp?M?A/E/J/G?U 86

HIV-1?Gp?M?B/F?U 87

Sequence microorganism sequence sequence

Show # number

HIV-1?Gp?M?A，CRF01AEU 88

HIV-1?Gp?M?B/GU 89

HIV-1?Gp?M?CRF01AE/BU 90

HIV-1?Gp?M?A2/DU 91

HIV-1?Gp?M?A，F，G，H，JU?92

HIV-1?Gp?M?A/D/GU 93

HIV-1?Gp?N?U 94

HIV-1?Gp?O?U 95

HIV-2?U 96

HIV-1 Gp M A1 blood subgroup URC 97

HIV-1 Gp M A2 blood subgroup URC 98

HIV-1 Gp M B hypotype URC 99

HIV-1 Gp M C hypotype URC 100

HIV-1 Gp M D hypotype URC 101

HIV-1 Gp M F1 hypotype URC 102

HIV-1 Gp M F2 hypotype URC 103

HIV-1 Gp M G hypotype URC 104

HIV-1 Gp M H hypotype URC 105

HIV-1 Gp M J hypotype URC 106

HIV-1 Gp M K hypotype URC 107

HIV-1?Gp?M?CRFA/EURC 108

HIV-1?Gp?M?A/GURC 109

HIV-1?Gp?M?A/BURC 110

HIV-1?Gp?M?A/G/IURC 111

HIV-1?Gp?M?F/DURC 112

HIV-1?Gp?M?A/G/JURC 113

HIV-1?Gp?M?C/BURC 114

HIV-1?Gp?M?B/CURC 115

Sequence microorganism sequence sequence

Show # number

HIV-1?Gp?MA/F/G?URC 116

HIV-1?Gp?MC/DU?RC 117

HIV-1?Gp?MA/E/J/GURC 118

HIV-1?Gp?MB/FU?RC 119

HIV-1?Gp?MA，CRF01AEURC 120

HIV-1?Gp?MB/GU?RC 121

HIV-1?Gp?MCRF01AE/BU?RC 122

HIV-1?Gp?MA2/DU?RC 123

HIV-1?Gp?MA，F，G，H，JURC 124

HIV-1?Gp?MA/D/GURC 125

HIV-1?Gp?NURC 126

HIV-1?Gp?OURC 127

HIV-2?U?RC 128

54 influenza virus A type influenza virus fragments 11

A type influenza virus fragment 22

A type influenza virus fragment 33

A type influenza virus fragment 44

A type influenza virus fragment 55

A type influenza virus fragment 66

A type influenza virus fragment 77

A type influenza virus fragment 88

Type B influenza virus HA 9

Type B influenza virus NP 10

Type B influenza virus PB1 T 11

Type B influenza virus PB2 T 12

Type B influenza virus NBBA T 13

Type B influenza virus M1BM2 T 14

Type B influenza virus PA T 15

Sequence microorganism sequence sequence

Show # number

Type B influenza virus NS1 NS2 T 16

Type B influenza virus HA H1N1 T 17

Type B influenza virus HA H2N2 T 18

Type B influenza virus HA H3N2 T 19

Type B influenza virus HA H4N2 T 20

Type B influenza virus HA H5N1 T 21

Type B influenza virus HA H6N2 T 22

Type B influenza virus HA H7N1 T 23

Type B influenza virus HA H8N4 T 24

Type B influenza virus HA H9N2 T 25

Type B influenza virus HA H10N7 T 26

Type B influenza virus HA H11N2 T 27

Type B influenza virus HA H12N1 T 28

Type B influenza virus HA H13N2 T 29

Type B influenza virus HA H14 T 30

Type B influenza virus HA H15N2 T 31

Type B influenza virus HA H16N3 T 32

Type B influenza virus NA H1N1 T 33

Type B influenza virus NA H5N1 T 34

Type B influenza virus NA H3N2 T 35

Type B influenza virus NA H3N3 T 36

Type B influenza virus NA H8N4 T 37

Type B influenza virus NA H6N5 T 38

Type B influenza virus NA H4N6 T 39

Type B influenza virus NA H7N7 T 40

Type B influenza virus NA H3N8 T 41

Type B influenza virus NA H2N9 T 42

A type influenza virus fragment 1 T RC 43

Sequence microorganism sequence sequence

Show # number

A type influenza virus fragment 2 T RC 44

A type influenza virus fragment 3 T RC 45

A type influenza virus fragment 4 T RC 46

A type influenza virus fragment 5 T RC 47

A type influenza virus fragment 6 T RC 48

A type influenza virus fragment 7 T RC 49

A type influenza virus fragment 8 T RC 50

Type B influenza virus HA T RC 51

Type B influenza virus NP T RC 52

Type B influenza virus PB1 T RC 53

Type B influenza virus PB2 T RC 54

Type B influenza virus NB BA T RC 55

Type B influenza virus M1 BM2 T RC 56

Type B influenza virus PA T RC 57

Type B influenza virus NS1 NS2 T RC 58

Type B influenza virus HA H1N1 T RC 59

Type B influenza virus HA H2N2 T RC 60

Type B influenza virus HA H3N2 T RC 61

Type B influenza virus HA H4N2 T RC 62

Type B influenza virus HA H5N1 T RC 63

Type B influenza virus HA H6N2 T RC 64

Type B influenza virus HA H7N1 T RC 65

Type B influenza virus HA H8N4 T RC 66

Type B influenza virus HA H9N2 T RC 67

Type B influenza virus HA H10N7 T RC 68

Type B influenza virus HA H11N2 T RC 69

Type B influenza virus HA H12N1 T RC 70

Type B influenza virus HA H13N2 T RC 71

Sequence microorganism sequence sequence

Show # number

Type B influenza virus HA H14 T RC 72

Type B influenza virus HA H15N2 T RC 73

Type B influenza virus HA H16N3 T RC 74

Type B influenza virus NA H1N1 T RC 75

Type B influenza virus NA H5N1 T RC 76

Type B influenza virus NA H3N2 T RC 77

Type B influenza virus NA H8N4 T RC 78

Type B influenza virus NA H6N5 T RC 79

Type B influenza virus NA H4N6 T RC 80

Type B influenza virus NA H7N7 T RC 81

Type B influenza virus NA H3N8 T RC 82

Type B influenza virus NA H2N9 T RC 83

A type influenza virus fragment 1 U 84

A type influenza virus fragment 2 U 85

A type influenza virus fragment 3 U 86

A type influenza virus fragment 4 U 87

A type influenza virus fragment 5 U 88

A type influenza virus fragment 6 U 89

A type influenza virus fragment 7 U 90

A type influenza virus fragment 8 91

Type B influenza virus HA U 92

Type B influenza virus NP U 93

Type B influenza virus PB1 U 94

Type B influenza virus PB2 U 95

Type B influenza virus NB NA U 96

Type B influenza virus M1 BM2 U 97

Type B influenza virus PA U 98

Type B influenza virus NS1 NS2 U 99

Sequence microorganism sequence sequence

Show # number

Type B influenza virus HA H1N1 U 100

Type B influenza virus HA H2N2 U 101

Type B influenza virus HA H3N2 U 102

Type B influenza virus HA H4N2 U 103

Type B influenza virus HA H5N1 U 104

Type B influenza virus HA H6N2 U 105

Type B influenza virus HA H7N1 U 106

Type B influenza virus HA H8N4 U 107

Type B influenza virus HA H9N2 U 108

Type B influenza virus HA H10N7 U 109

Type B influenza virus HA H11N2 U 110

Type B influenza virus HA H12N1 U 111

Type B influenza virus HA H13N2 U 112

Type B influenza virus HA H14 U 113

Type B influenza virus HA H15N2 U 114

Type B influenza virus HA H16N3 U 115

Type B influenza virus NA H1N1 U 116

Type B influenza virus NA H5N1 U 117

Type B influenza virus NA H3N2 U 118

Type B influenza virus NA H8N4 U 119

Type B influenza virus NA H6N5 U 120

Type B influenza virus NA H4N6 U 121

Type B influenza virus NA H7N7 U 122

Type B influenza virus NA H3N8 U 123

Type B influenza virus NA H2N9 U 124

A type influenza virus fragment 1U RC 125

A type influenza virus fragment 2U RC 126

A type influenza virus fragment 3U RC 127

Sequence microorganism sequence sequence

Show # number

A type influenza virus fragment 4 U RC 128

A type influenza virus fragment 5 U RC 129

A type influenza virus fragment 6 U RC 130

A type influenza virus fragment 7 U RC 131

A type influenza virus fragment 8 U RC 132

Type B influenza virus HA U RC 133

Type B influenza virus NP U RC 134

Type B influenza virus PB1 U RC 135

Type B influenza virus PB2 U RC 136

Type B influenza virus NB BA U RC 137

Type B influenza virus M1 BM2 U RC 138

Type B influenza virus PA U RC 139

Type B influenza virus NS1 N S2 U RC 140

Type B influenza virus HA H2N2 U RC 141

Type B influenza virus HA H3N2 U RC 142

Type B influenza virus HA H4N2 U RC 143

Type B influenza virus HA H5N1 U RC 144

Type B influenza virus HA H6N2 U RC 145

Type B influenza virus HA H7N1 U RC 146

Type B influenza virus HA H8N4 U RC 147

Type B influenza virus HA H9N2 U RC 148

Type B influenza virus HA H10N7 U RC 149

Type B influenza virus HA H11N2 U RC 150

Type B influenza virus HA H12N1 U RC 151

Type B influenza virus HA H13N2 U RC 152

Type B influenza virus HA H14 U RC 153

Type B influenza virus HA H15N2 U RC 154

Type B influenza virus HA H16N3 U RC 155

Sequence microorganism sequence sequence

Show # number

Type B influenza virus NA H1N1 U RC 156

Type B influenza virus NA H5N1 U RC 157

Type B influenza virus NA H3N2 U RC 158

Type B influenza virus NA H6N5 U RC 159

Type B influenza virus NA H7N7 U RC 160

Type B influenza virus NA H3N8 U RC 161

Type B influenza virus NA H2N2 U RC 162

55 BK virus BK virus U 1

BK virus T 2

BK virus U RC 3

BK virus T RC 456 crust horse virus crust horse forest virus (Barmah Forest virus) U 1

(Barmah) crust horse forest virus T 2

Crust horse forest virus U RC 3

Crust horse forest virus T RC 4

Tin pest poison U 1 in the tin pest poison card in 57 cards

(Calicivirus) tin pest poison T 2 in the card

Tin pest poison U RC 3 in the card

Tin pest poison T RC 4 in the card

58 colorado tick fever colorado tick fever virus fragments, 1 U 1

Virus colorado tick fever viral fragment 1 T 2

Colorado tick fever virus fragment 1 U RC 3

Colorado tick fever virus fragment 1 T RC 4

Colorado tick fever virus fragment 2 U 5

Colorado tick fever virus fragment 2 T 6

Colorado tick fever virus fragment 2 U RC 7

Colorado tick fever virus fragment 2 T RC 8

Colorado tick fever virus fragment 3 U 9

Sequence microorganism sequence sequence

Show # number

Colorado tick fever virus fragment 3 T 10

Colorado tick fever virus fragment 3 U RC 11

Colorado tick fever virus fragment 3 T RC 12

Colorado tick fever virus fragment 4 U 13

Colorado tick fever virus fragment 4 T 14

Colorado tick fever virus fragment 4 U RC 15

Colorado tick fever virus fragment 4 T RC 16

Colorado tick fever virus fragment 5 U 17

Colorado tick fever virus fragment 5 T 18

Colorado tick fever virus fragment 5 U RC 19

Colorado tick fever virus fragment 5 T RC 20

Colorado tick fever virus fragment 6 U 21

Colorado tick fever virus fragment 6 T 22

Colorado tick fever virus fragment 6 U RC 23

Colorado tick fever virus fragment 6 T RC 24

Colorado tick fever virus fragment 7 U 25

Colorado tick fever virus fragment 7 T 26

Colorado tick fever virus fragment 7 U RC 27

Colorado tick fever virus fragment 7 T RC 28

Colorado tick fever virus fragment 8 U 29

Colorado tick fever virus fragment 8 T 30

Colorado tick fever virus fragment 8 U RC 31

Colorado tick fever virus fragment 8 T RC 32

Colorado tick fever virus fragment 9 U 33

Colorado tick fever virus fragment 9 T 34

Colorado tick fever virus fragment 9 U RC 35

Colorado tick fever virus fragment 9 T RC 36

Colorado tick fever virus fragment 10 U 37

Sequence microorganism sequence sequence

Show # number

Colorado tick fever virus fragment 10 T 38

Colorado tick fever virus fragment 10 U RC 39

Colorado tick fever virus fragment 10 T RC 40

Colorado tick fever virus fragment 11 U 41

Colorado tick fever virus fragment 11 T 42

Colorado tick fever virus fragment 11 U RC 43

Colorado tick fever virus fragment 11 T RC 44

Colorado tick fever virus fragment 12 U 45

Colorado tick fever virus fragment 12 T 46

Colorado tick fever virus fragment 12 U RC 47

Colorado tick fever virus fragment 12 T RC 48

59 foot and mouth disease virus foot and mouth disease virus A U 1

Foot and mouth disease virus A T 2

Foot and mouth disease virus A U RC 3

Foot and mouth disease virus A T RC 4

Foot and mouth disease virus Asia 1 type U 5

Foot and mouth disease virus Asia 1 type T 6

Foot and mouth disease virus Asia 1 type U RC 7

Foot and mouth disease virus Asia 1 type T RC 8

Foot and mouth disease virus C U 9

Foot and mouth disease virus C T 10

Foot and mouth disease virus C U RC 11

Foot and mouth disease virus C T RC 12

Foot and mouth disease virus O U 13

Foot and mouth disease virus O T 14

Foot and mouth disease virus O U RC 15

Foot and mouth disease virus O T RC 16

Foot and mouth disease virus SAT1U 17

Sequence microorganism sequence sequence

Show # number

Foot and mouth disease virus SAT 1 T 18

Foot and mouth disease virus SAT 1 U RC 19

Foot and mouth disease virus SAT 1 T RC 20

Foot and mouth disease virus SAT 2 U 21

Foot and mouth disease virus SAT 2 T 22

Foot and mouth disease virus SAT 2 U RC 23

Foot and mouth disease virus SAT 2 T RC 24

Foot and mouth disease virus SAT 3 U 25

Foot and mouth disease virus SAT 3 T 26

Foot and mouth disease virus SAT 3 U RC 27

Foot and mouth disease virus SAT 3 T RC 28

60 GB Hepatitis virus GB C-type virus C C U 1

GB C-type virus C C T 2

GB C-type virus C C U RC 3

GB C-type virus C C T RC 4

61 Heng Dela virus Heng Dela virus U 1

(Hendra virus) Heng Dela virus T 2

Heng Dela virus U RC 3

Heng Dela virus T RC 4

62 human adenovirus A type human adenovirus U 1

A type human adenovirus T 2

A type human adenovirus U RC 3

A type human adenovirus T RC 4

Type B human adenovirus U 5

Type B human adenovirus T 6

Type B human adenovirus U RC 7

Type B human adenovirus T RC 8

C type human adenovirus U 9

Sequence microorganism sequence sequence

Show # number

C type human adenovirus T 10

C type human adenovirus RC 11

C type human adenovirus T RC 12

D type human adenovirus U 13

D type human adenovirus T 14

D type human adenovirus U RC 15

D type human adenovirus T RC 16

E type human adenovirus U 17

E type human adenovirus T 18

E type human adenovirus U RC 19

E type human adenovirus T RC 20

F type human adenovirus U 21

F type human adenovirus T 22

F type human adenovirus U RC 23

F type human adenovirus T RC 24

63 human astrovirus virus human astrovirus virus U 1

Human astrovirus virus T 2

Human astrovirus virus U RC 3

Human astrovirus virus T RC 4

The human bocavirus U 1 of 64 human bocavirus

Human bocavirus T 2

Human bocavirus U RC 3

Human bocavirus T RC 4

65 human coronary virus human coronary virus 229E U 1

Human coronary virus 229E T 2

Human coronary virus 229E U RC 3

Human coronary virus 229E TRC 4

Human coronary virus HKU1 A type U 5

Sequence microorganism sequence sequence

Show # number

Human coronary virus HKU1 A type T 6

Human coronary virus HKU1 A type U RC 7

Human coronary virus HKU1 A type T RC 8

Human coronary virus NL63 U 9

Human coronary virus NL63 T 10

Human coronary virus NL63 U RC 11

Human coronary virus NL63 T RC 12

Human coronary virus OU43 U 13

Human coronary virus OU43 T 14

Human coronary virus OU43 U RC 15

Human coronary virus OU43 T RC 16

66 human intestines virus human intestine virus-A U 1

Human intestine virus-AT 2

Human intestine's virus-A-U RC 3

Human intestine's virus-A-T RC 4

Human intestine's virus-B U 5

Human intestine's virus-B T 6

Human intestine's virus-B U RC 7

Human intestine's virus-B T RC 8

Human intestine's virus-C U 9

Human intestine's virus-C T 10

Human intestine's virus-C U RC 11

Human intestine's virus-C T RC 12

Human intestine's virus-D U 13

Human intestine's virus-D T 14

Human intestine's virus-D U RC 15

Human intestine's virus-D T RC 16

67 nerpes vinrus hominis nerpes vinrus hominis-1 U 1

Sequence microorganism sequence sequence

Show # number

Nerpes vinrus hominis-1 T 2

Nerpes vinrus hominis-1 U RC 3

Nerpes vinrus hominis-1 T RC 4

Nerpes vinrus hominis-2 U 5

Nerpes vinrus hominis-2 T 6

Nerpes vinrus hominis-2 U RC 7

Nerpes vinrus hominis-2 T RC 8

Nerpes vinrus hominis-3 U 9

Nerpes vinrus hominis-3 T 10

Nerpes vinrus hominis-3 U RC 11

Nerpes vinrus hominis-3 T RC 12

Nerpes vinrus hominis-4 U 13

Nerpes vinrus hominis-4 T 14

Nerpes vinrus hominis-4 U RC 15

Nerpes vinrus hominis-4 T RC 16

Nerpes vinrus hominis-5 (AD169) U 17

Nerpes vinrus hominis-5 (AD169) T 18

Nerpes vinrus hominis-5 (AD169) U RC 19

Nerpes vinrus hominis-5T (AD169) RC 20

Nerpes vinrus hominis-6A U 21

Nerpes vinrus hominis-6A T 22

Nerpes vinrus hominis-6A URC 23

Nerpes vinrus hominis-6A T RC 24

Nerpes vinrus hominis-6B U 25

Nerpes vinrus hominis-6B T 26

Nerpes vinrus hominis-6B URC 27

Nerpes vinrus hominis-6B T RC 28

Nerpes vinrus hominis-7 U 29

Sequence microorganism sequence sequence

Show # number

Nerpes vinrus hominis-7 T 30

Nerpes vinrus hominis-7 U RC 31

Nerpes vinrus hominis-7 T RC 32

Nerpes vinrus hominis-8 U 33

Nerpes vinrus hominis-8 T 34

Nerpes vinrus hominis-8 U RC 35

Nerpes vinrus hominis-8 T RC 36

68 human metapneumovirus human metapneumovirus U 1

Human metapneumovirus T 2

Human metapneumovirus U RC 3

Human metapneumovirus T RC 4

69 human parainfluenza patient class parainfluenza virus-1 U 1

Poison human parainfluenza virus-1 T 2

Human parainfluenza virus-1 U RC 3

Human parainfluenza virus-1 T RC 4

Human parainfluenza virus-2 U 5

Human parainfluenza virus-2 T 6

Human parainfluenza virus-2 U RC 7

Human parainfluenza virus-2 T RC 8

Human parainfluenza virus-3 U 9

Human parainfluenza virus-3 T 10

Human parainfluenza virus-3 U RC 11

Human parainfluenza virus-3 T RC 12

The lonely viral U 1 of the lonely patient's class of 70 human intestines enteron aisle

The lonely viral T 2 of poison human intestine

The lonely viral U RC 3 of human intestine

The lonely viral T RC 4 of human intestine

71 human rhinovirus human rhinovirus-A U 1

Sequence microorganism sequence sequence

Show # number

Human rhinovirus-A T 2

Human rhinovirus-A U RC 3

Human rhinovirus-A T RC 4

Human rhinovirus-B U 5

Human rhinovirus-B T 6

Human rhinovirus-B U RC 7

Human rhinovirus-B T RC 8

72 human airways close human RSV U 1

The human RSV T 2 of cellular virus

Human RSV U RC 3

Human RSV T RC 4

73 Measles virus Measles virus U 1

Measles virus T 2

Measles virus RC U 3

Measles virus RC T 4

74 mumps virus mumps virus U 1

Mumps virus T 2

Mumps virus RC U 3

Mumps virus RC T 4

75 norovirus norovirus U 1

Norovirus T 2

Norovirus RC U 3

Norovirus RC T 4

76 Norwalk virus Norwalk virus U 1

Norwalk virus T 2

Norwalk virus RC U 3

Norwalk virus RC T 4

77 assays for parvovirus B 19 assays for parvovirus B 19 U 1

Sequence microorganism sequence sequence

Show # number

Assays for parvovirus B 19 T 2

Assays for parvovirus B 19 RC U 3

Assays for parvovirus B 19 RC T 4

The sick poliovirus U 1 of 78 poliomyelitis

Poison poliovirus T 2

Poliovirus RC U 3

Poliovirus RC T 4

79 rabies virus rabies virus U 1

Rabies virus T 2

Rabies virus RC U 3

Rabies virus RC T 4

80 ross river virus ross river virus U 1

Ross river virus T 2

Ross river virus RC U 3

Ross river virus RC T 4

81 rotavirus rotavirus A NSP1 U 1

Rotavirus A NSP1 T 2

Rotavirus A NSP1 U RC 3

Rotavirus A NSP1 T RC 4

Rotavirus B NSP1 U 5

Rotavirus B NSP1 T 6

Rotavirus B NSP1 U RC 7

Rotavirus B NSP1 T RC 8

Rotavirus C NSP1 U 9

Rotavirus C NSP1 T 10

Rotavirus C NSP1 U RC 11

Rotavirus C NSP1 T RC 12

Rotavirus A NSP2 U 13

Sequence microorganism sequence sequence

Show # number

Rotavirus A NSP2 T 14

Rotavirus A NSP2 U RC 15

Rotavirus A NSP2 T RC 16

Rotavirus B NSP2 U 17

Rotavirus B NSP2 T 18

Rotavirus B NSP2 U RC 19

Rotavirus B NSP2 T RC 20

Rotavirus C NSP2 U 21

Rotavirus C NSP2 T 22

Rotavirus C NSP2 U RC 23

Rotavirus C NSP2 T RC 24

Rotavirus A NSP3 U 25

Rotavirus A NSP3 T 26

Rotavirus A NSP3 U RC 27

Rotavirus A NSP3 T RC 28

Rotavirus B NSP3 U 29

Rotavirus B NSP3 T 30

Rotavirus B NSP3 U RC 31

Rotavirus B NSP3 T RC 32

Rotavirus C NSP3 U 33

Rotavirus C NSP3 T 34

Rotavirus C NSP3 U RC 35

Rotavirus C NSP3 T RC 36

Rotavirus A NSP4 U 37

Rotavirus A NSP4 T 38

Rotavirus A NSP4 U RC 39

Rotavirus A NSP4 T RC 40

Rotavirus B NSP4 U 41

Sequence microorganism sequence sequence

Show # number

Rotavirus B NSP4 T 42

Rotavirus B NSP4 U RC 43

Rotavirus B NSP4 T RC 44

Rotavirus C NSP4 U 45

Rotavirus C NSP4 T 46

Rotavirus C NSP4 U RC 47

Rotavirus C NSP4 T RC 48

Rotavirus A NSP5 U 49

Rotavirus A NSP5 T 50

Rotavirus A NSP5 U RC 51

Rotavirus A NSP5 T RC 52

Rotavirus B NSP5 U 53

Rotavirus B NSP5 T 54

Rotavirus B NSP5 U RC 55

Rotavirus B NSP5 T RC 56

Rotavirus C NSP5 U 57

Rotavirus C NSP5 T 58

Rotavirus C NSP5 U RC 59

Rotavirus C NSP5 T RC 60

Rotavirus A VP1 U 61

Rotavirus AVP1 T 62

Rotavirus AVP1 U RC 63

Rotavirus A VP1 T RC 64

Rotavirus C VP1 U 65

Rotavirus C VP1 T 66

Rotavirus C VP1 U RC 67

Rotavirus CVP1 T RC 68

Rotavirus A VP2 U 69

Sequence microorganism sequence sequence

Show # number

Rotavirus A VP2 T 70

Rotavirus A VP2 U RC 71

Rotavirus A VP2 T RC 72

Rotavirus B VP2 U 73

Rotavirus B VP2 T 74

Rotavirus BVP2 U RC 75

Rotavirus B VP2 T RC 76

Rotavirus C VP2 U 77

Rotavirus C VP2 T 78

Rotavirus C VP2 U RC 79

Rotavirus C VP2 T RC 80

Rotavirus A VP3 U 81

Rotavirus A VP3 T 82

Rotavirus A VP3 U RC 83

Rotavirus A VP3 T RC 84

Rotavirus C VP3 U 85

Rotavirus C VP3 T 86

Rotavirus C VP3 U RC 87

Rotavirus C VP3 T RC 88

Rotavirus A VP4 U 89

Rotavirus A VP4 T 90

Rotavirus A VP4 U RC 91

Rotavirus A VP4 T RC 92

Rotavirus B VP4 U 93

Rotavirus B VP4 T 94

Rotavirus B VP4 U RC 95

Rotavirus B VP4 T RC 96

Rotavirus C VP4 U 97

Sequence microorganism sequence sequence

Show # number

Rotavirus C VP4 T 98

Rotavirus C VP4 U RC 99

Rotavirus C VP4 T RC 100

Rotavirus A VP6 U 101

Rotavirus A VP6 T 102

Rotavirus A VP6 U RC 103

Rotavirus A VP6 T RC 104

Rotavirus B VP6 U 105

Rotavirus B VP6 T 106

Rotavirus B VP6 U RC 107

Rotavirus B VP6 T RC 108

Rotavirus C VP6 U 109

Rotavirus C VP6 T 110

Rotavirus C VP6 U RC 111

Rotavirus C VP6 T RC 112

Rotavirus A VP7 U 113

Rotavirus A VP7 T 114

Rotavirus A VP7 U RC 115

Rotavirus A VP7 T RC 116

Rotavirus B VP7 U 117

Rotavirus B VP7 T 118

Rotavirus B VP7 U RC 119

Rotavirus B VP7 T RC 120

Rotavirus C VP7 U 121

Rotavirus C VP7 T 122

Rotavirus C VP7 U RC 123

Rotavirus C VP7 T RC 124

The crown sick sars coronavirus U 1 of 82 SARS

Sequence microorganism sequence sequence

Show # number

Poison sars coronavirus T 2

Sars coronavirus RC U 3

Sars coronavirus RC T 4

83 TT virus TT virus U 1

TT virus T 2

TT virus RC U 3

TT virus RC T 4

84 TTV microvirus TTV microvirus U 1

TTV microvirus T 2

TTV microvirus U RC 3

TTV microvirus T RC 4

85 west nile virus west nile virus U 1

West nile virus T 2

West nile virus U RC 3

West nile virus T RC 4

86 alphavirus alphavirus U 1

Alphavirus T 2

Alphavirus U RC 3

Alphavirus T RC 4

87 camelpox virus camelpox virus U 1

Camelpox virus T 2

Camelpox virus U RC 3

Camelpox virus T RC 4

88 vaccinia virus vaccinia virus U 1

Vaccinia virus T 2

Vaccinia virus U RC 3

Vaccinia virus T RC 4

89 Coxiella burnetii Coxiella burnetii U 1

Sequence microorganism sequence sequence

Show # number

(Coxiella Coxiella burnetii T 2

Burnetii) Coxiella burnetii U RC 3

Coxiella burnetii T RC 4

90 Crimeas-the Congo crimean-Congo hemorrhagic fever virus S U 1

Hemorrhagic fever virus crimean-Congo hemorrhagic fever virus S T 2

Crimean-Congo hemorrhagic fever virus S U RC 3

Crimean-Congo hemorrhagic fever virus S T RC 4

Crimean-Congo hemorrhagic fever virus L U 5

Crimean-Congo hemorrhagic fever virus L T 6

Crimean-Congo hemorrhagic fever virus L U RC 7

Crimean-Congo hemorrhagic fever virus L T RC 8

Crimean-Congo hemorrhagic fever virus M U 9

Crimean-Congo hemorrhagic fever virus M T 10

Crimean-Congo hemorrhagic fever virus M U RC 11

Crimean-Congo hemorrhagic fever virus M T RC 12

91 dengue fever virus dengue fever virus-1U 1

Dengue fever virus-1 T 2

Dengue fever virus-1 U RC 3

Dengue fever virus-1 T RC 4

Dengue fever virus-2 U 5

Dengue fever virus-2 T 6

Dengue fever virus-2 U RC 7

Dengue fever virus-2 T RC 8

Dengue fever virus-3 U 9

Dengue fever virus-3 T 10

Dengue fever virus-3 U RC 11

Dengue fever virus-3 T RC 12

Dengue fever virus-4 U 13

Sequence microorganism sequence sequence

Show # number

Dengue fever virus-4 T 14

Dengue fever virus-4 U RC 15

Dengue fever virus-4 T RC 16

The sick Eastern equine encephalitis virus U 1 of 92 east equine encephalitis

Poison Eastern equine encephalitis virus T 2

Eastern equine encephalitis virus U RC 3

Eastern equine encephalitis virus T RC 4

93 Ebola virus the Sudan Ebola virus U 1

The Sudan Ebola virus T 2

The Sudan Ebola virus U RC 3

The Sudan Ebola virus T RC 4

The viral U 5 of Rui Sidun Ebola (Ebola-Reston)

Rui Sidun Ebola virus T 6

Rui Sidun Ebola virus U RC 7

Rui Sidun Ebola virus T RC 8

The viral U 9 of Zaire Ebola (Ebola-Zaire)

Zaire Ebola virus T 10

Zaire Ebola virus U RC 11

Zaire Ebola virus T RC 12

94 Marburg virus Marburg virus U 1

Marburg virus T 2

Marburg virus U RC 3

Marburg virus T RC 4

95 guanarito virus guanarito virus L U 1

Guanarito virus L T 2

Guanarito virus L U RC 3

Guanarito virus L T RC 4

Guanarito virus S U 5

Sequence microorganism sequence sequence

Show # number

Guanarito virus S T 6

Guanarito virus S U RC 7

Guanarito virus S T RC 8

96 Hantaan virus Hantaan virus M U 1

Hantaan virus M T 2

Hantaan virus M U RC 3

Hantaan virus M T RC 4

Hantaan virus L U 5

Hantaan virus L T 6

Hantaan virus L U RC 7

Hantaan virus L T RC 8

Hantaan virus S U 9

Hantaan virus S T 10

Hantaan virus S U RC 11

Hantaan virus S T RC 12

97 hantaan virus hantaan virus L U 1

Hantaan virus L T 2

Hantaan virus L U RC 3

Hantaan virus L T RC 4

Hantaan Virus M U 5

Hantaan Virus M T 6

Hantaan virus L M RC 7

Hantaan virus L M RC 8

Hantaan virus S U 9

Hantaan virus S T 10

Hantaan virus S U RC 11

Hantaan virus S T RC 12

98 japanese encephalitis virus japanese encephalitis virus U 1

Sequence microorganism sequence sequence

Show # number

Japanese encephalitis virus T 2

Japanese encephalitis virus U RC 3

Japanese encephalitis virus T RC 4

99 Junin virus Junin virus S U 1

Junin virus S T 2

Junin virus S U RC 3

Junin virus S T RC 4

Junin virus L U 5

Junin virus L T 6

Junin virus L U RC 7

Junin virus L T RC 8

100 lassa virus lassa virus L U 1

Lassa virus L T 2

Lassa virus L U RC 3

Lassa virus L T RC 4

Lassa virus S U 5

Lassa virus S T 6

Lassa virus S U RC 7

Lassa virus S T RC 8

101 machupo virus machupo virus L U 1

Machupo virus L T 2

Machupo virus L U RC 3

Machupo virus L T RC 4

Machupo virus S U 5

Machupo virus S T 6

Machupo virus S U RC 7

Machupo virus S T RC 8

102 monkey pox virus monkey pox virus U 1

Sequence microorganism sequence sequence

Show # number

Monkey pox virus T 2

Monkey pox virus U RC 3

Monkey pox virus T RC 4

The 103 scorching disease of Lay valley head scorching viral U 1 of Lay valley head not

Poison is the scorching viral T 2 of Lay valley head not

The scorching viral U RC 3 of Lay valley head not

The scorching viral T RC 4 of Lay valley head not

104 Nipah virus Nipah virus U 1

Nipah virus T 2

Nipah virus U RC 3

Nipah virus T RC 4

105 Rift Valley fever virus Rift Valley fever virus S U 1

Rift Valley fever virus S T 2

Rift Valley fever virus S U RC 3

Rift Valley fever virus S T RC 4

Rift Valley fever virus M U 5

Rift Valley fever virus M T 6

Rift Valley fever virus M U RC 7

Rift Valley fever virus M T RC 8

Rift Valley fever virus L U 9

Rift Valley fever virus L T 10

Rift Valley fever virus L U RC 11

Rift Valley fever virus L T RC 12

106 Sabias virus Sabia virus S U 1

Sabia's virus S T 2

Sabia's virus S U RC 3

Sabia's virus S T RC 4

Sabia's virus L U 5

Sequence microorganism sequence sequence

Show # number

Sabia's virus L T 6

Sabia's virus L U RC 7

Sabia's virus L T RC 8

107 Xin Nuobai C-type virus C Xin Nuobai C-type virus C LU 1

(Sin Nombre Xin Nuobai C-type virus C L T 2

Virus) Xin Nuobai C-type virus C LU RC 3

Xin Nuobai C-type virus C L T RC 4

Xin Nuobai C-type virus C S U 5

Xin Nuobai C-type virus C S T 6

Xin Nuobai C-type virus C S U RC 7

Xin Nuobai C-type virus C S T RC 8

Xin Nuobai C-type virus C M U 9

Xin Nuobai C-type virus C M T 10

Xin Nuobai C-type virus C M U RC 11

Xin Nuobai C-type virus C M T RC 12

108 variola major virus variola major virus U 1

Variola major virus T 2

Variola major virus U RC 3

Variola major virus T RC 4

109 milk-pox virus milk-pox virus U 1

Milk-pox virus T 2

Milk-pox virus U RC 3

Milk-pox virus T RC 4

110 Venezuela horse brain Venezuelan equine encephalitis virus U 1

Scorching viral Venezuelan equine encephalitis virus T 2

Venezuelan equine encephalitis virus U RC 3

Venezuelan equine encephalitis virus T RC 4

The sick Western equine encephalitis virus U 1 of 111 Western equine encephalitis

Sequence microorganism sequence sequence

Show # number

Poison Western equine encephalitis virus T 2

Western equine encephalitis virus U RC 3

Western equine encephalitis virus T RC 4

112 yellow fever virus yellow fever virus U 1

Yellow fever virus T 2

Yellow fever virus U RC 3

Yellow fever virus T RC 4

^*The cochain of deriving that all cytosine(Cyt)s of U are all replaced by uridylic

^*The modification cochain that all uridylics of T are all replaced by VITAMIN B4

^*Chain under the deriving that all cytosine(Cyt)s of U RC are all replaced by uridylic

^*Chain under the modification that all uridylics of T RC are all replaced by VITAMIN B4

It will be understood by those skilled in the art that and to carry out multiple change and/or improvement to the present invention shown in the specific embodiments, and do not depart from the spirit or scope of the present invention of extensive elaboration.Therefore, consider that in all respects the present embodiment all is illustrative and nonrestrictive.

Claims (107)

1. the derivative nucleic acids of hepatitis C virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:76 in the sequence table 51, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

2. the derivative nucleic acids of acinetobacter or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 1, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence hybridization or its part hybridization under stringent condition.

3. derivative nucleic acids of bacillus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:12 in the sequence table 2, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

4. the derivative nucleic acids of Bacteroides or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 3, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

5. the derivative nucleic acids of Bartonella or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:8 in the sequence table 4, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

6. the derivative nucleic acids of Bordetella or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 5, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

7. the derivative nucleic acids of Borrelia or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 6, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

8. the derivative nucleic acids of Brucella or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:8 in the sequence table 7, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

9. the derivative nucleic acids of Campylobacter or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 8, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

10. the derivative nucleic acids of chlamydiaceae or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:8 in the sequence table 9, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

11. derivative nucleic acids of fusobacterium or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:39 in the sequence table 10, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

12. the derivative nucleic acids of corynebacterium or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 11, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

13. colibacillary derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 12, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

14. derivative nucleic acids or modification of nucleic acids that dust Garrick body belongs to, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 13, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

15. the derivative nucleic acids of enterococcus spp or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 14, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

16. the derivative nucleic acids of fusobacterium or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 15, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

17. the derivative nucleic acids of hemophilus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 16, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

18. derivative nucleic acids of screw rod Pseudomonas or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 17, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

19. the derivative nucleic acids of legionella or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 18, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

20. the derivative nucleic acids of leptospira or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 19, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

21. derivative nucleic acids of listeria or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 20, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

22. the derivative nucleic acids of Mycobacterium or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 21, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

23. the derivative nucleic acids of Mycoplasma or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 22, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

24. the derivative nucleic acids of Neisseria or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 23, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

25. the derivative nucleic acids of Nocardia or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 24, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

26. derivative nucleic acids of Rhodopseudomonas or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 25, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

27. the derivative nucleic acids of Dermacentroxenus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 26, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

28. the derivative nucleic acids of salmonella or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 27, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

29. the derivative nucleic acids of serratia or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 28, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

30. the derivative nucleic acids of Shigella or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 29, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

31. the derivative nucleic acids of Staphylococcus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:52 in the sequence table 30, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

32. the derivative nucleic acids of streptococcus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:16 in the sequence table 31, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

33. the derivative nucleic acids of streptomyces or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 32, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

34. the derivative nucleic acids of treponema or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 33, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

35.Trophermya the derivative nucleic acids of sp or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 34, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

36. the derivative nucleic acids of plasmodium or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:60 in the sequence table 35, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

37. the derivative nucleic acids of Aspergillus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:8 in the sequence table 36, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

38. candidal derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:24 in the sequence table 37, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

39. the derivative nucleic acids of genera cryptococcus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 38, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

40. the derivative nucleic acids of Paracoccidioides or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 39, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

41. the derivative nucleic acids of Rhizopus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 40, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

42. derivative nucleic acids of Mark Lewis-Francis Pseudomonas or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 41, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

43. the derivative nucleic acids of Vibrio or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 42, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

44. the derivative nucleic acids of yersinia's genus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 43, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

45.JC derivative nucleic acids of polyomavirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 44, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

46. the derivative nucleic acids of Andean virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 46, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

47. the derivative nucleic acids of hepatitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:24 in the sequence table 52, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

48. derivative nucleic acids of human immunodeficiency virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:128 in the sequence table 53, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

49. derivative nucleic acids of influenza virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:162 in the sequence table 54, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

50.BK the derivative nucleic acids or the modification of nucleic acids of virus, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 55, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

51.Barmah the derivative nucleic acids or the modification of nucleic acids of virus, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 56, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

52. the derivative nucleic acids or the modification of nucleic acids of tin pest poison in the card, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 57, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

53. the derivative nucleic acids of colorado tick fever virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:48 in the sequence table 58, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

54. derivative nucleic acids of foot and mouth disease virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:28 in the sequence table 59, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

55.GB derivative nucleic acids of Hepatitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 60, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

56. the derivative nucleic acids of Heng Dela virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 61, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

57. the derivative nucleic acids of human adenovirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:24 in the sequence table 62, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

58. the derivative nucleic acids of human astrovirus virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 63, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

59. the derivative nucleic acids of human bocavirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 64, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

60. human coronary virus's derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 65, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

61. the derivative nucleic acids of human intestine's virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 66, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

62. nerpes vinrus hominis's derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:36 in the sequence table 67, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

63. the derivative nucleic acids of human metapneumovirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 68, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

64. human parainfluenza virus's derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 69, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

65. the derivative nucleic acids or the modification of nucleic acids of the lonely virus of human intestine, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 70, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

66. human rhinovirus's derivative nucleic acids or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 71, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

67. the derivative nucleic acids of human airway syncytial virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 72, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

68. derivative nucleic acids of Measles virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 73, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

69. derivative nucleic acids of mumps virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 74, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

70. the derivative nucleic acids of norovirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 75, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

71. the derivative nucleic acids of Norwalk virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 76, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

72. the derivative nucleic acids of parvovirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 77, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

73. the derivative nucleic acids of poliovirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 78, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

74. the derivative nucleic acids of rabies virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 79, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

75. the derivative nucleic acids of ross river virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 80, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

76. the derivative nucleic acids of rotavirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:124 in the sequence table 81, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

77.SARS derivative nucleic acids of coronavirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 82, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

78.TT the derivative nucleic acids or the modification of nucleic acids of virus, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 83, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

79.TTV derivative nucleic acids of microvirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 84, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

80. derivative nucleic acids of west nile virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 85, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

81. the derivative nucleic acids of alphavirus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ IDNO:1 to SEQ ID NO:4 in the sequence table 86, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

82. the derivative nucleic acids of camelpox virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 87, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

83. derivative nucleic acids of vaccinia virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:4 in the sequence table 88, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

84. derivative nucleic acids or modification of nucleic acids that the Cox body belongs to, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 89, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

85. the derivative nucleic acids of crimean-Congo hemorrhagic fever virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 90, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

86. the derivative nucleic acids of dengue fever virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:16 in the sequence table 91, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

87. the derivative nucleic acids of Eastern equine encephalitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 92, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

88. derivative nucleic acids of Ebola virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 93, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

89. derivative nucleic acids of Marburg virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 94, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

90. the derivative nucleic acids of guanarito virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 95, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

91. the derivative nucleic acids of Hantaan virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:12 in the sequence table 96, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

92. the derivative nucleic acids of hantaan virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:12 in the sequence table 97, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

93. derivative nucleic acids of japanese encephalitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 97, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

94. the derivative nucleic acids of Junin virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQID NO:1 to SEQ ID NO:8 in the sequence table 99, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

95. derivative nucleic acids of lassa virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 100, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

96. the derivative nucleic acids of machupo virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 101, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

97. the derivative nucleic acids of monkey pox virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 102, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

98. the not derivative nucleic acids or the modification of nucleic acids of the scorching virus of Lay valley head, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 103, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

99. the derivative nucleic acids of Nipah virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 104, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

100. the derivative nucleic acids of Rift Valley fever virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 105, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

101. the derivative nucleic acids of Sabia's virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:8 in the sequence table 106, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

102. the derivative nucleic acids of Xin Nuobai C-type virus C or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:12 in the sequence table 107, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

103. the derivative nucleic acids of variola major virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 108, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

104. the derivative nucleic acids of milk-pox virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 109, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

105. derivative nucleic acids of Venezuelan equine encephalitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 110, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

106. derivative nucleic acids of Western equine encephalitis virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 111, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

107. derivative nucleic acids of yellow fever virus or modification of nucleic acids, its sequence are selected from by the sequence of SEQ ID NO:1 to SEQ ID NO:4 in the sequence table 112, comprise at least about the part of the described sequence of 20 Nucleotide and the group that can form with the nucleic acid molecule of described sequence or its part hybridization under stringent condition.

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