CN112410443A - Biological population marker for identifying elderly individuals and obtaining method and application thereof - Google Patents
Biological population marker for identifying elderly individuals and obtaining method and application thereof Download PDFInfo
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The present invention relates to a biological population marker for identifying an elderly individual, the biological population marker comprising: escherichia coli, Achillea rosea, Alsteripes anderdonokii, Alsteripes shahii, Arteriaria flacheri Finegondii, Alsteripes sp AP11, Bacteroides coprinus caccae, Odoribacterium odoratum sp lance, Anacardiaceae parahaemophilus var versicolor, Anacardia rapamibacter piscicola, Parabacteroides gordonii and Pseudococcus pseudopekinensis Subdoliguru sp _4_3_54A2 FAA. The biological population markers of the present invention, which were determined by comparative analysis and verification of differences in abundance of various intestinal microorganisms in stool samples of elderly and non-elderly individuals (healthy children or age-matched healthy individuals), were used to determine the probability of an individual being in an ultra-advanced state.
Description
Technical Field
The invention relates to the technical field of biomarkers, in particular to a biological population marker for identifying an elderly individual, and an obtaining method and application thereof.
Background
With the development of social economy, the life expectancy of Chinese people is steadily increased, and the proportion of old people is continuously increased. There is a high probability of various sub-health states in the elderly, such as asthenia (frailty) and inflammatory aging (inflamaging), and thus, it has become an important issue in the present generation to promote the health level of the elderly and thus promote their socioeconomic participation. Among the various options for improving the sub-health status of the elderly, the micro-ecological approach is a relatively mild, less invasive and less risky intervention, but requires extensive and intensive research into the characteristics of the flora and other relevant factors of the relevant population, in particular of the elderly. The correlation factors of advanced age include genetic, socioeconomic, environmental and other major categories, and meanwhile, more and more evidences show that the intestinal flora is closely related to the advanced age. Intestinal microorganisms play an important role in intestinal epithelial cells, including the formation of a microbial barrier to prevent colonization by pathogenic bacteria, and participation in immunoregulatory and metabolic functions. Research shows that the imbalance of intestinal flora can cause the injury of organisms in different forms, and pathogenic microorganisms can cause intestinal inflammatory reaction by activating and recognizing receptors, adsorbing and secreting enterotoxins or invading and the like. Changes in the number, structure and stability of intestinal microorganisms, especially imbalance of flora, can alter normal physiological functions to cause intestinal diseases, thereby affecting health and life expectancy.
Our metagenomic studies of elderly people show that the characteristics of the intestinal flora of elderly individuals exhibit an overall tendency to worsen compared to the control group, with obvious characteristics including an increase in escherichia coli, a decrease in Faecalibacterium prausnitzii and bifidobacterium longum, two major probiotics, and an increase in the lipopolysaccharide (lipolytica) synthesis pathway and the anionic antimicrobial peptide (Cationic peptide) resistance pathway in the functional elements. Therefore, we speculate that among microorganisms highly enriched in elderly individuals, a plurality of species strains are closely associated with the sub-health status of the elderly. Thus, markers of advanced flora do not only provide a means of identifying individuals of very advanced age, but also allow the production of microecological diagnostic interventions against inflammatory aging.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a biological population marker for identifying an aged individual, and an obtaining method and an identification method thereof.
In order to achieve the purpose, the invention adopts the technical scheme that:
in a first aspect of the invention, there is provided a biological population marker for identifying an elderly individual, the biological population marker comprising:
escherichia coli, Achromobacter anatipes anderdonokii, Achromobacter sartorius shahii, Achromobacter vannamei finegoldii, Achromobacter aligenes _ sp _ AP11, Bacteroides coprococcae, Achromobacter odoratum sp _ lantanicus, Anacardia fragilis var variabilis Pyramidobacter piscolens, Parabacteroides gordonii and Pseudococcus pseudopekinensis Subdoliguru _ sp _4_3_54A2 FAA;
wherein the relative abundance interval of Escherichia coli is 6.51 × 10 according to 95% confidence interval-2～1.14×10-1The relative abundance interval of the Alistipes ondendokii of the another branchlet is 2.54 multiplied by 10-2～4.81×10-2The relative abundance interval of the Alistipes shahii is 1.31 multiplied by 10-2～2.00×10-2The relative abundance interval of the Alistipes finegoldii of the another Branch of Van's disease is 3.66 multiplied by 10-3～6.51×10-3The relative abundance interval of the Alistipes _ sp _ AP11 of the other branch bacteria is 3.14 multiplied by 10-3～5.71×10-3The relative abundance interval of the Bacteroides coprocola is 1.53 multiplied by 10-2～3.37×10-2The relative abundance interval of the anobacterium viscidula is 8.75 multiplied by 10-3～1.46×10-2The relative abundance interval of the fishy-smell conical bacillus piscolens is 1.06 multiplied by 10-3～1.04×10-2The range of relative abundance of paradisella gordonii is 2.79X 10-3～7.18×10-3The relative abundance interval of the pseudomonas subvarigranulum _ sp _4_3_54A2FAA is 2.61 × 10-3～7.18×10-3。
In a second aspect of the present invention, there is provided a method for obtaining a biological population marker as described above, comprising the steps of:
s1, determining the abundance of various microorganisms of the biological population markers in a stool sample of an elderly individual;
s2, respectively comparing the abundances of various microorganisms of the biological population markers determined in S1 with the abundances of the various microorganisms in a control group, and obtaining the biological population markers according to the comparison result;
wherein the control group comprises a group of stool samples from children of the individual and a group of stool samples from healthy individuals of an age consistent with the age of children of the individual.
Preferably, the step S1 includes:
s1-1, obtaining sequencing data of a nucleic acid sequence in a stool sample of an individual, wherein the sequencing data comprises a plurality of reads;
s1-2, determining assembly fragments contained by various microorganisms of the biological population marker;
s1-3, respectively determining the abundance of each assembled fragment in the gene set according to the sequencing data, wherein the abundance of each assembled fragment contained in each microorganism of the biological species group marker is respectively determined;
s1-4, respectively determining the abundance of each microorganism of the biological population marker according to the abundance of the determined assembly fragments.
Preferably, the step S1-2 includes:
and respectively comparing the assembled fragments in the gene set with the reference sequences of various microorganisms, wherein if the similarity of the assembled fragments with the reference sequence of one microorganism is more than or equal to 90%, the assembled fragments come from the microorganism.
Preferably, the abundance of the microorganism is the median or average of the abundances of all assembled fragments comprised by that species of microorganism.
In a third aspect of the invention there is provided a use of a biological population marker as hereinbefore described for identifying an elderly individual, the step of identifying the elderly individual comprising:
b1, determining the abundance of each microorganism of the biological population markers in the fecal sample of the individual;
b2, respectively comparing the abundances of various microorganisms of the biological species group marker determined in B1 with relative abundance intervals thereof, and determining the state of the individual according to the obtained comparison result;
wherein the states include an aging state and a non-aging state.
Preferably, the step B1 includes:
b1-1, obtaining sequencing data of a nucleic acid sequence in a stool sample of the individual, the sequencing data comprising a plurality of reads;
b1-2, determining the assembly fragments contained by various microorganisms of the biological population marker;
b1-3, respectively determining the abundance of each assembled fragment in the gene set according to the sequencing data, including respectively determining the abundance of the assembled fragments contained by each microorganism of the biological species group marker;
b1-4, respectively determining the abundance of each microorganism of the biological population marker according to the abundance of the determined assembly fragments.
Preferably, the step B1-2 includes:
and respectively comparing the assembled fragments in the gene set with the reference sequences of various microorganisms, wherein if the similarity of the assembled fragments with the reference sequence of one microorganism is more than or equal to 90%, the assembled fragments come from the microorganism.
Preferably, the abundance of the microorganism is the median or average of the abundances of all assembled fragments comprised by that species of microorganism.
Preferably, the step B2 includes:
determining the status of the individual as an advanced status if the abundances of the various microorganisms in the biological population marker determined in step B1 all fall within the relative abundance interval.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the biological population markers of the present invention were determined by comparative analysis and validation of differences in abundance of various intestinal microorganisms in stool samples from elderly and non-elderly individuals (healthy children or age-matched healthy individuals). The biological population marker is significantly enriched in the stool sample of the advanced age group compared to the stool sample of the control group, by significant enrichment is meant that the abundance of each of the microorganisms comprising the biological population marker in the advanced age group is statistically significantly higher or significantly, substantially higher than the abundance in the control group compared to the abundance in the control group. Thus, the biological population markers are capable of determining the probability that an individual is in an ultra-old state.
Drawings
FIG. 1 is a schematic representation of an assay flow for screening to identify a biomarker of a biological population in an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The invention is further described with reference to the following drawings and specific examples, which are not intended to be limiting.
Example 1
A biological marker is a cellular, biochemical or molecular change that can be detected from a biological medium. Biological media include various body fluids, tissues, cells, feces, hair, breath, and the like.
The abundance of a certain microorganism refers to the abundance of that microorganism in a certain population of microorganisms, for example, the abundance of that microorganism in a population of gut microorganisms, and can be expressed as the amount of that microorganism in that population.
A first aspect of this embodiment provides a biological population marker for identifying an elderly individual, the biological population marker comprising:
escherichia coli, Achromobacter anatipes anderdonokii, Achromobacter sartorius shahii, Achromobacter vannamei finegoldii, Achromobacter aligenes _ sp _ AP11, Bacteroides coprococcae, Achromobacter odoratum sp _ lantanicus, Anacardia fragilis var variabilis Pyramidobacter piscolens, Parabacteroides gordonii and Pseudococcus pseudopekinensis Subdoliguru _ sp _4_3_54A2 FAA;
wherein the relative abundance interval of Escherichia coli is 6.51 × 10 according to 95% confidence interval-2～1.14×10-1The relative abundance interval of the Alistipes ondendokii of the another branchlet is 2.54 multiplied by 10-2～4.81×10-2The relative abundance interval of the Alistipes shahii is 1.31 multiplied by 10-2～2.00×10-2The relative abundance interval of the Alistipes finegoldii of the another Branch of Van's disease is 3.66 multiplied by 10-3～6.51×10-3The relative abundance interval of the Alistipes _ sp _ AP11 of the other branch bacteria is 3.14 multiplied by 10-3～5.71×10-3The relative abundance interval of the Bacteroides coprocola is 1.53 multiplied by 10-2～3.37×10-2The relative abundance interval of the anobacterium viscidula is 8.75 multiplied by 10-3～1.46×10-2The relative abundance interval of the fishy-smell conical bacillus piscolens is 1.06 multiplied by 10-3～1.04×10-2The range of relative abundance of paradisella gordonii is 2.79X 10-3～7.18×10-3The relative abundance interval of the pseudomonas subvarigranulum _ sp _4_3_54A2FAA is 2.61 × 10-3～7.18×10-3。
The biological population markers of the present invention were determined by comparative analysis and validation of differences in abundance of various intestinal microorganisms in stool samples from elderly and non-elderly individuals (healthy children or age-matched healthy individuals). The biological population marker is significantly enriched in the stool sample of the advanced age group compared to the stool sample of the control group, by significant enrichment is meant that the abundance of each of the microorganisms comprising the biological population marker in the advanced age group is statistically significantly higher or significantly, substantially higher than the abundance in the control group compared to the abundance in the control group. Thus, the biological population markers are capable of determining the probability that an individual is in an ultra-old state.
This example provides a use of a biological population marker as described above for identifying an elderly individual, the step of identifying the elderly individual comprising:
b1, determining the abundance of various microorganisms of the biological population markers in the fecal sample of the individual:
obtaining sequencing data for a nucleic acid sequence in a fecal sample of the individual, the sequencing data comprising a plurality of reads; determining the assembled fragments comprised by each microorganism in the biological population marker; determining the abundance of each assembled fragment in the gene set separately from the sequencing data, including determining the abundance of assembled fragments contained by each microorganism in the biological population marker separately; determining abundances of each microorganism in the biological population marker based on the determined abundances of the assembled fragments, respectively.
The sequencing data is obtained by sequencing nucleic acid sequences in a sample, and the sequencing can select but is not limited to a semiconductor sequencing technology platform such as PGM, Ion Proton and BGISEQ-100 platform, a sequencing-by-synthesis technology platform such as Hiseq and Miseq sequence platform of Illumina company and a single-molecule real-time sequencing platform such as PacBio sequence platform according to different selected sequencing platforms. The sequencing mode can be single-ended sequencing or double-ended sequencing, and the obtained off-machine data are sequencing and reading fragments which are called reads (reads).
The assembling fragments contained in various microorganisms in the biological population marker are determined by performing Blat comparison on the assembling fragments in the gene set and a microorganism reference sequence, and judging whether the assembling fragments are from the microorganisms according to the similarity degree of the assembling fragments and the microorganism reference sequence. The reference sequence refers to a predetermined sequence, and may be any reference template of a biological category to which a sample to be tested belongs or which is obtained in advance, for example, if the target is a microorganism in the sample to be tested, the reference sequence may select a reference genome of various microorganisms in an NCBI database and/or a DACC enteric genome disclosed in HMP or MetaHIT project, and further, a resource pool including more reference sequences may be configured in advance, for example, a more similar sequence may be selected or determined to be assembled as the reference sequence according to factors such as the state of an individual from which the sample to be tested originates, a region, and the like. Determining the assembled fragments comprised by each microorganism in the biological population marker includes: and (3) respectively comparing the assembled fragments in the gene set with the reference sequences of various microorganisms, and determining that the assembled fragments with the similarity of more than or equal to 90 percent of the reference sequences of a microorganism are from the microorganism. More strictly, it is determined that an assembled fragment with a similarity greater than or equal to 95% to a reference sequence of a microorganism is from that microorganism.
The alignment can be performed by using known alignment software, such as SOAP, BWA, TeraMap, etc., in the alignment process, the alignment parameters are generally set, one or a pair of reads (reads) is set to allow at most s base mismatches (mismatches), for example, s is set to be less than or equal to 2, and if more than s bases in the reads are mismatched, it is considered that the reads cannot be aligned to the assembled fragment. The obtained comparison result includes the comparison condition between each read and each assembly fragment, including information as to whether the read can compare the last one or some assembly fragments, uniquely compare only one assembly fragment or multiple assembly fragments, compare the position of the assembly fragment, compare the unique position of the assembly fragment or multiple positions, and the like. The alignment was performed using SOAPalign 2.21 with the parameters set to-r 2-m 100-x 1000.reads are aligned to the gene set, which can be divided into two parts: a) uniquely comparing the reads of the last assembly fragment, and calling the reads as unique reads (U); b) the multiple assembled fragments were aligned and the reads were called multiple reads (M). For a given assembly fragment G, i.e., gene G in the gene set, the abundance is Ab (G), which is related to unique reads and multiple reads, Ab (U) and Ab (M) in the above formulas are the abundances of unique reads and multiple reads of the assembly fragment G, respectively. Each multiple reads has a specific gene abundance coefficient Co, and assuming that a multiple read aligns to N assembly fragments, the Co of the multiple read can be calculated by the following formula:
that is, for such multiplereds, the sum of the abundance of unique reads of the N genes (i.e., assembled fragments in the gene set) aligned therewith is taken as the denominator.
According to an embodiment of the present invention, said step of determining the abundance of each microorganism in said biological population marker based on said determined abundance of the assembled fragments, respectively, is a median or average of the abundances of all assembled fragments comprised by said species of microorganism.
B2, respectively comparing the abundances of various microorganisms of the biological species marker determined in B1 with the relative abundance intervals thereof, and determining the status of the individual according to the obtained comparison results, wherein the status comprises an advanced status and a non-advanced status:
and if the predetermined confidence interval of the abundance of a certain microorganism in the biological species marker in the advanced age group intersects with the predetermined confidence interval of the abundance of the certain microorganism in the control group, determining the predetermined interval of the certain microorganism as a part of the difference set of the two. The confidence interval refers to the estimated interval of the overall parameter constructed from the sample statistics. In statistics, the confidence interval (confidence interval) of a probability sample is an interval estimate for some overall parameter of the sample. The confidence interval exhibits the extent to which the true value of this parameter has a certain probability of falling around the measurement. The confidence interval is given byThe degree of confidence in the measured value of the measured parameter, i.e. the "certain probability" required above. This probability is called the confidence level. According to the embodiment of the invention, the predetermined confidence intervals are 95% confidence intervals, and the predetermined interval of Escherichia coli in the biological population marker is 6.51 multiplied by 10-2～1.14×10-1The predetermined interval of the Alisipes onerdokii in the biological population marker is 2.54 multiplied by 10-2～4.81×10-2(ii) a The predetermined interval of Bacteroides caccae in the biological population marker is 1.53 × 10-2～3.37×10-2(ii) a The predetermined interval of the microorganism Alisipes shahii in the biological population marker is 1.31 multiplied by 10-2～2.00×10-2(ii) a The predetermined interval of the odorobacterium visceral splanchnocardius in the biological population marker is 8.75 × 10-3～1.46×10-2. It should be noted that, depending on the purpose or requirement, there may be different requirements on the confidence level of the result of determining the state of an individual, and a person skilled in the art may choose different significance levels (α), i.e. different probabilities of making errors, such that the confidence level of the determined state of an individual is 1- α. For example, it is reliable to determine that the individual is in the determined state 95% using the present embodiment.
The method is based on detecting the abundance of various microorganisms in the biological population markers in the fecal sample of the individual, respectively comparing the abundances of the various detected microorganisms with the abundances of the various detected microorganisms in the control group, and determining the probability that the individual is an elderly individual or a non-elderly individual according to the obtained comparison result.
All or a portion of the steps of any of the above methods for determining the status of an individual using a biological population marker may be performed using a device/system comprising corresponding unit function modules that are detachable, or the method may be programmed, stored on a machine-readable medium, and executed by a machine.
According to an embodiment of the present invention, there is provided an apparatus for determining a status of an individual using a biological population marker in any of the above embodiments of the present invention, the apparatus being configured to perform all or part of the steps of the method for determining a status of an individual using a biological population marker in any of the above embodiments of the present invention, the apparatus comprising: a data input unit for inputting data; a data output unit for outputting data; a processor for executing an executable program, the executing of the executable program comprising performing the method for determining the status of an individual according to one embodiment of the present inventors; and the storage unit is connected with the data input unit, the data output unit and the processor and is used for storing data, wherein the storage unit comprises the executable program. The above description of the technical features and advantages of the method for determining the status of an individual using biological population markers according to any embodiment of the present invention is equally applicable to the apparatus according to this aspect of the present invention, and will not be repeated herein.
According to another embodiment of the present invention, there is provided a method of classifying a plurality of individuals using the biological population markers of any of the above embodiments of the present invention, the method comprising: determining the state of each individual by using the method for determining the state of the individual in any embodiment of the invention; and classifying the individuals according to the obtained states of the individuals. The method can distinguish a plurality of individuals or a plurality of unknown stool samples according to different states of the individuals, and is convenient for classification and marking management. In addition, the above description of the technical features and advantages of the method for determining the status of an individual using a biological population marker in any embodiment of the present invention is also applicable to the apparatus of the aspect of the present invention, and will not be repeated herein.
By utilizing the medicament or the functional food of the embodiment, the determined biological population markers are reasonably and effectively applied, the growth of beneficial bacteria in the intestinal tract is supported and/or potential pathogenic bacteria in the intestinal tract are inhibited, the defect of the intestinal tract barrier can be prevented, the intestinal tract microecological structure is improved and recovered, and the medicament or the functional food has important significance for assisting in reducing the blood endotoxin level and/or improving the sub-health state of the old.
By utilizing the method for producing or screening the microecologics capable of improving the health level and the life quality of the old, the determined biological population markers are reasonably and effectively applied for screening, so that the medicine capable of supporting the growth of intestinal beneficial bacteria and/or inhibiting intestinal potential pathogenic bacteria can be obtained, the defect of an intestinal barrier can be prevented, the microecological structure of the intestinal tract can be improved and recovered, and the method has important significance for assisting in reducing the blood endotoxin level and/or relieving the sub-health state.
The method and/or apparatus of the present invention is described in detail below with reference to specific embodiments. Reagents, sequences (linkers, tags, and primers), software, and instruments referred to in the following examples are conventional commercial products or open sources, such as the transcriptome library construction kit from Illumina, unless otherwise submitted.
Example 2
In this example, the inventors studied the fecal microflora composition by performing a correlation analysis of intestinal microflora microorganisms from fecal samples of 116 elderly persons, 232 orthologous children, and 77 healthy individuals of age equivalent to elderly persons and children. In general, a total of about 1084.87Gb of sequencing data was downloaded for each sample in the control group. Quantitative metagenomic analysis showed that 14,993 genes showed significant differences (FDR <0.05) in a large number of patients and healthy controls.
1. Subject recruitment
116 elderly people and 232 children (1-2 children per elderly person) were recruited from hospitals of junior people in Jiangsu, and 77 health controls comparable to the ages of children of elderly people were recruited from hospitals of the tenth people in Shanghai. Stool samples were collected from subjects, and each sample yielded on average 5Gb high quality sequencing data.
2. Determination and identification of biological population markers
Referring to the experimental procedure of fig. 1, identification of relevant biomarkers of high age was determined.
2.1 basic processing of sequencing data
Sequencing raw data has been subjected to quality control and de-hosting, but there are many short reads in the data, and reads with length less than 60nt in the raw data are filtered in pairs.
3. Screening biological population markers
All 116 samples of elderly and 232 samples of women were divided into experimental group and control group 1. A threshold (fdr <0.05) was used to find 61 species with significant differences between the control and aged groups. 40 of the microorganisms were enriched in the elderly, and 21 were enriched in the control.
As can be seen from Table 1, Escherichia coli and Alisipes onderdonkii having intersection in 95% confidence intervals of abundance in the offspring group and in the elderly individual group, and when the individual state was determined by using a marker comprising all or a part of the three, the intersection of 95% confidence intervals of abundance in the two groups of three microorganisms was removed to obtain a predetermined interval judged by comparison of their abundance, and Escherichia coli having a predetermined interval of 6.51X 10-2～1.14×10-1The predetermined interval of the Alistipes onerdokii is 2.54 × 10-2～4.81×10-2。
TABLE 1 comparison of enriched species in all elderly individuals with the cohort of offspring
Example 3
In order to verify that the species marker identified in example 1 can be used as a biological population marker, 116 elderly and 77 healthy individuals of age comparable to children and adults of advanced age were used for verification. Wherein the determination of the abundance of the species is made with reference to the steps of the above example. The obtained different species are cross-verified with the results obtained in example 1, the generated intersection species are biological population markers, and 10 species with the highest abundance are selected in the patent.
In addition, the inventor further combines any one, two, three or all four, three or four of the other 4 microorganisms determined in example 1 to perform state verification detection on a large number of stool samples of elderly people as markers, wherein the state can be determined to be more than 90% consistent with the recorded state by using the method of the example.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (10)
1. A biological population marker for identifying an elderly individual, the biological population marker comprising:
escherichia coli, Achromobacter anatipes anderdonokii, Achromobacter sartorius shahii, Achromobacter vannamei finegoldii, Achromobacter aligenes _ sp _ AP11, Bacteroides coprococcae, Achromobacter odoratum sp _ lantanicus, Anacardia fragilis var variabilis Pyramidobacter piscolens, Parabacteroides gordonii and Pseudococcus pseudopekinensis Subdoliguru _ sp _4_3_54A2 FAA;
wherein the relative abundance interval of Escherichia coli is 6.51 × 10 according to 95% confidence interval-2～1.14×10-1The relative abundance interval of the Alistipes ondendokii of the another branchlet is 2.54 multiplied by 10-2～4.81×10-2The relative abundance interval of the Alistipes shahii is 1.31 multiplied by 10-2～2.00×10-2The relative abundance interval of the Alistipes finegoldii of the another Branch of Van's disease is 3.66 multiplied by 10-3～6.51×10-3The relative abundance interval of the Alistipes _ sp _ AP11 of the other branch bacteria is 3.14 multiplied by 10-3～5.71×10-3The relative abundance interval of the Bacteroides coprocola is 1.53 multiplied by 10-2～3.37×10-2The relative abundance interval of the anobacterium viscidula is 8.75 multiplied by 10-3～1.46×10-2The relative abundance interval of the fishy-smell conical bacillus piscolens is 1.06 multiplied by 10-3～1.04×10-2The range of relative abundance of paradisella gordonii is 2.79X 10-3～7.18×10-3The relative abundance interval of the pseudomonas subvarigranulum _ sp _4_3_54A2FAA is 2.61 × 10-3～7.18×10-3。
2. A method of obtaining a biological population marker according to claim 1, comprising the steps of:
s1, determining the abundance of various microorganisms of the biological population markers in a stool sample of an elderly individual;
s2, respectively comparing the abundances of various microorganisms of the biological population markers determined in S1 with the abundances of the various microorganisms in a control group, and obtaining the biological population markers according to the comparison result;
wherein the control group comprises a group of stool samples from children of the individual and a group of stool samples from healthy individuals of an age consistent with the age of children of the individual.
3. The obtaining method according to claim 2, wherein the step S1 includes:
s1-1, obtaining sequencing data of a nucleic acid sequence in a stool sample of an individual, wherein the sequencing data comprises a plurality of reads;
s1-2, determining assembly fragments contained by various microorganisms of the biological population marker;
s1-3, respectively determining the abundance of each assembled fragment in the gene set according to the sequencing data, wherein the abundance of each assembled fragment contained in each microorganism of the biological species group marker is respectively determined;
s1-4, respectively determining the abundance of each microorganism of the biological population marker according to the abundance of the determined assembly fragments.
4. The obtaining method according to claim 3, wherein the step S1-2 includes:
and respectively comparing the assembled fragments in the gene set with the reference sequences of various microorganisms, wherein if the similarity of the assembled fragments with the reference sequence of one microorganism is more than or equal to 90%, the assembled fragments come from the microorganism.
5. The method of claim 2, wherein the abundance of the microorganism is the median or average of the abundances of all assembled fragments contained in the species of microorganism.
6. Use of the biological population marker of claim 1 for identifying an elderly individual, the step of identifying an elderly individual comprising:
b1, determining the abundance of each microorganism of the biological population markers in the fecal sample of the individual;
b2, respectively comparing the abundances of various microorganisms of the biological species group marker determined in B1 with relative abundance intervals thereof, and determining the state of the individual according to the obtained comparison result;
wherein the states include an aging state and a non-aging state.
7. The use according to claim 6, wherein said step B1 comprises:
b1-1, obtaining sequencing data of a nucleic acid sequence in a stool sample of the individual, the sequencing data comprising a plurality of reads;
b1-2, determining the assembly fragments contained by various microorganisms of the biological population marker;
b1-3, respectively determining the abundance of each assembled fragment in the gene set according to the sequencing data, including respectively determining the abundance of the assembled fragments contained by each microorganism of the biological species group marker;
b1-4, respectively determining the abundance of each microorganism of the biological population marker according to the abundance of the determined assembly fragments.
8. The use according to claim 7, wherein said step B1-2 comprises:
and respectively comparing the assembled fragments in the gene set with the reference sequences of various microorganisms, wherein if the similarity of the assembled fragments with the reference sequence of one microorganism is more than or equal to 90%, the assembled fragments come from the microorganism.
9. The use of claim 6, wherein the abundance of said microorganism is the median or average of the abundances of all assembled fragments comprised by that species of microorganism.
10. The use according to claim 6, wherein said step B2 comprises:
determining the status of the individual as an advanced status if the abundances of the various microorganisms in the biological population marker determined in step B1 all fall within the relative abundance interval.
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