JP5422934B2 - Palindromic structure detection system in genome sequence - Google Patents

Description

  The present invention relates to a palindrome structure detection system in a genome sequence that detects a palindrome structure included in the genome sequence at high speed.

The genome sequence data of DNA (Deoxyribonucleic acid) is an enormous data group in which sequences of four types of bases A (adenine), T (thymine), G (guanine), and C (cytosine) are arranged in 100 million units in series. .
In recent years, genome sequence data on human genes and genes of other important organisms has been rapidly analyzed.
In the public data of the genome sequence, the above A, T, C, and G4 types of bases are merely enumerated, and rather than knowing which part of the sequence contains important data, The fact is that it is hardly known in which region the gene exists.

In particular, in single-stranded DNA and RNA (Ribonucleic acid), a stem loop structure pamphlet (the same reading is obtained even before and after “Takeya Bakeyake”, “Shinbushi”), etc. (palindromic) The structure of m (messenger) RNA is changed by not binding the repressor protein.
For example, in the example shown in FIG. 20, the mRNA of the sequence of FIG. 20 (a) (corresponding to the generation of tryptophan) is as shown in FIG. 20 (b) when a repressor protein such as ribosome is not bound. It has a stem loop structure.
However, the mRNA of the sequence of FIG. 20 (a) has the stem loop structure of FIG. 21 (a) when a large amount of tributophan is supplied and is present at a high concentration, while the demand for tryptophan is large and present at a low concentration. In this case, the structure shown in FIG.

As described above, various types of stem-loop structures in different palindrome structures, that is, specific states have been found at present.
If this stem-loop structure is used, the actual genome sequence cannot be read, and the site cannot be analyzed.
Searching for a site where a stem loop structure lurking in the genomic sequence of mRNA or DNA may occur has important implications such as searching for the status of amino acid production in the ribosome corresponding to the genomic sequence.
In particular, mRNA generated by PCR (Polymerase Chain Reaction) can easily form a stem loop structure, and in order to know what kind of stem loop structure it is possible that the stem loop structure of the mRNA may occur. It is necessary to know a certain part in advance.

For this reason, since base A and base T and base C and base G are in a complementary relationship to form a base pair, by analyzing the base sequence in the genome sequence, any part of the genome sequence It is detected whether it is a palindromic structure and a part that may cause a stem loop structure (Patent Document 1).
JP 2005-316924 A

However, in the above-described conventional example, an algorithm performed by computer processing is described, but only the sequence relationship of bases A, T, G, and C is shown. There is a drawback that it is not possible to determine whether it is a palindrome structure.
Conventionally, numbers such as 1, 2, 3, and 4 for bases A, T, G, and C, respectively, are detected by computer processing to detect where palindrome structures are included. (In the case of 2 bits, for example, A = 00, T = 01, G = 10, C = 11), and an operation for detecting the palindrome structure is performed. .

When the bases are defined as described above in the operation for detecting the palindrome structure, the complementary relations in the detection results output as a sequence of bases A, T, G, and C are difficult to visually understand. I cannot intuitively judge what the enumeration of bases means.
The present invention has been made in view of such circumstances, and it is possible to easily analyze a large amount of data in a genome sequence, and the analysis result of palindrome structure in the genome sequence has a visually important part. An object of the present invention is to provide a palindromic structure detection apparatus for genome sequences obtained as a result that can be discriminated immediately.

  The palindrome structure detection system in the genome sequence of the present invention assigns the same number to each base that forms a base pair in the genome sequence, and attaches a sign with a different polarity to each base, thereby identifying the palindrome structure in the genome sequence. This is a palindromic structure detection system that detects a base / number conversion unit that replaces each base in the input genome sequence with a number with a corresponding sign, and in the genome sequence from both ends in the analysis range toward the center. A base pair generation unit that shifts the bases one by one and combines n bases from each end in the analysis range corresponding to the positions from both ends to generate n base pairs set in advance; , N first adders for independently adding numbers corresponding to the bases of the base pairs output from the base pair generator, and outputs of the first adders, and the addition result Having an absolute value unit for calculating an absolute value, a palindromic calculation unit and a second adder for adding the absolute values of the addition result in the analysis range.

  The palindrome structure detection system in the genome sequence of the present invention is a detection signal that detects the presence of the palindrome structure by the n base pairs when the second adder outputs 0. To do.

  The palindrome structure detection system in the genome sequence of the present invention is characterized in that a plurality of palindromic operation units are provided for each analysis range having a different number of bases.

  The palindrome structure detection system in the genome sequence of the present invention is characterized in that the analysis range in the genome sequence is sequentially shifted one base at a time, and palindrome structure detection processing is performed at each shift.

  In the palindrome structure detection system in the genome sequence of the present invention, the palindrome calculation unit includes non-addition bases sandwiched by n bases from both ends within the analysis range (contains palindrome bases included in the palindrome structure). A non-palindromic base) that detects the palindrome structure as an even number, the even palindromic operation unit having the first addition unit and the second addition unit, and n bases from both ends within the analysis range And an odd palindromic operation unit having a first addition unit and a second addition unit that detect a palindrome structure with an odd number of non-addition bases sandwiched between the first and second addition units.

  In the palindrome structure detection system in the genome sequence of the present invention, the detection result of the palindrome calculation unit for each analysis range in which the number of non-addition bases sandwiched between n bases from both ends is increased in base pair units. It is characterized in that the number of bases forming a pair in superposition and palindrome structure is obtained.

  The palindrome structure detection system in the genome sequence of the present invention provides a genome sequence for each palindrome operation unit in the analysis range in which the number of non-addition bases sandwiched between n bases from both ends is increased in units of base pairs. Has a storage unit for storing the detection results obtained by shifting the base by one base, the palindrome structure is detected in the genome sequence, and the analysis range having the same center is overlapped and output as the detected palindrome structure It is characterized by that.

The palindrome structure detection system in the genome sequence according to the present invention includes the even palindromic operation unit and the odd palindromic operation unit each having two input n first addition units and an absolute value provided for each addition unit. And an n-input second adder.
The palindrome structure detection system in the genome sequence of the present invention includes a database storing restriction enzymes corresponding to the base sequences constituting the palindrome structure, and the palindrome structure detected when the palindrome structure is detected. And a search unit that searches for the restriction enzyme corresponding to the base sequence of the sentence structure.

  As described above, according to the present invention, when detecting the presence or absence of a palindrome structure that may form a stem-loop structure, when forming the stem-loop structure, complementary bases forming each base pair are formed. Since the palindromic structure is detected by attaching the same number and different sign (+/-) to the bases in relation, analysis of a large amount of base data in the base genome sequence can be performed easily and at high speed. Moreover, the analysis result of palindrome structure in the genome sequence is obtained as a result that a visually important part can be immediately discriminated.

  The palindromic structure detection system in the genomic sequence of the present invention is a base that forms a base pair (base G and base C, or base A and base T (base U in RNA)) in the genomic sequence of DNA or RNA. The same number is assigned to each, and a symbol having a different polarity is assigned to each. For example, in this embodiment, “+1” is added to the base G, “−1” is added to the base C, and “ The palindrome structure detection system detects the palindrome structure in the genome sequence by attaching “−2” to the base T and “−2”.

That is, in the present invention, by assigning a number with a sign to each base and giving a complementary feature between the bases forming the base pair, the simple characters of the bases A, T (U), C, and G The list is easy to understand visually.
As a feature described above, the base pair is in a complementary relationship in which the base T is always combined with the base A and the base G is always combined with the base C.
In the present embodiment, as described above, the relationship between the complements in this base pair (complementary base pair) is represented by a sign relationship between + (plus) and-(minus) (a sign relationship with different polarity). .
In addition, in the base A and the base G that are purine bases, the molecular weight of the base G is larger, so the base G is expressed as “+2” and the base A is expressed as “+1”. The pyrimidine base represents the base C as “−2” and the base T as “−1”.

This indicates the complementary relationship, the classification of the base pair AT system, the base pair CG system, and the size of the molecular weight.
Base G Molecular weight 151 → +2 "010" with a sign in binary
Base A Molecular weight 135 → +1 Signed “001” in binary
Base T Molecular weight 126 → −1 Signed “101” in binary
Base C Molecular weight 111 → -2 Signed "110" in binary
As described above, each salt is represented by a base code bit and AT and GC classification bits.
In the first adder described later, this is calculated using the relationship of A (+1) + T (−1) = 0, G (+2) + C (−2) = 0, so that the structure of the stem loop is obtained. Extract.

  Then, the palindromic structure detection system in the genome sequence of the present invention is replaced with the base / number conversion unit that sequentially replaces each base in the input genome sequence with the corresponding number and the number with the sign. The palindromic operation unit that detects the palindrome structure from the signed numbers adds a base from the both ends in the analysis range consisting of a preset number of bases in the above-described genome sequence in the center direction in the analysis range. A base pair generator that generates n base pairs that are set in advance by combining n bases from each end within the analysis range corresponding to the positions from both ends, N number of first addition units for independently adding numbers corresponding to the bases of the base pairs output from the base pair generation unit, and outputs of the first addition units, Absolute An absolute value unit for calculating a, and a second adder for adding the absolute values of the addition result in the analysis range.

In general, a stem-loop structure appears remarkably at the end of t-RNA or m-RNA as shown in FIG.
In the random enumeration of characters A, T, C, and G indicating the base in FIG. 1A, it is difficult to detect a palindrome structure that may form a stem-loop structure.
However,
"A, C, G, C, G, T"
By converting the palindrome structure to the above-mentioned signed number,
"+1 (first), -2, +2, -2, +2, -1 (sixth)"
And an array of signed numbers.

In this array,
1st "+1" and 6th "-1"
2nd "-2" and 5th "+2"
3rd "+2" and 4th "-2"
As a base pair, it is understood that the addition result of the signed number corresponding to the base of any base pair becomes “0” when adding the signed number corresponding to the base of each base pair.
In other words, when the DNA sequence is read in sequence and the current position An and the previous An-m are targeted,
A _n + A _n−m = 0
A _n−1 + A _{n−m + 1} = 0
A _n−2 + A _{n−m + 2} = 0
It can be seen that there are palindrome structures where Here, m (integer) is the number of bases in the analysis range including a non-palindromic base in the center, and corresponds to this base with the base at the opposite position across the non-pain base as a base pair. Add signed numbers for each base pair.

For example,
When m = 5
A _n + A _n−5 = 0 A _n−1 + A _n−4 = 0 A _n−2 + A _n−3 = 0
When m = 6
A _n + A _n-6 = 0 A _n-1 + A _n-5 = 0 A _n-2 + A _n-4 = 0
When m = 7
A _n + A _n-7 = 0 A _n-1 + A _n-6 = 0 A _n-2 + A _n-5 = 0
A _n-3 + A _n-4 = 0
When m = 8
A _n + A _n-8 = 0 A _n-1 + A _n-7 = 0 A _n-2 + A _n-6 = 0
A _n−3 + A _n−5 = 0.

<First Embodiment>
The palindrome structure detection system in the genome sequence according to the first embodiment will be described below with reference to FIG. FIG. 2 is a block diagram showing a configuration example of the palindrome structure detection system in the genome sequence according to the first embodiment.
In the present embodiment, the analysis range of the palindrome structure is set as the structure of FIG. 2A composed of palindrome 3 (= r) base, non palindrome q base, palindrome 3 (= r) base, and the base sequence The palindrome structure is detected while sequentially shifting the analysis range by one base at a time.
The base / number conversion unit 1 replaces each base in the genome sequence inputted by shifting one base at a time in time series with a number with a corresponding code, that is, base G is “+2” and base A is “ +1 ", base C is converted to" -2 ", base T is converted to" -1 "and output.
For example, the shift register 150 sequentially adds the numbers with the signs inputted in time series from the base / number conversion unit 1 one by one in accordance with the timing at which the base / number conversion unit 1 outputs the numbers. Shift and output serially input numbers in parallel. The shift register 150 is configured to be able to shift by a number corresponding to the number of base sequences within the analysis range in the base pair generation unit 2 described later. A _n ... A _n−j to be described later is a parallel output of the shift register 150 (base sequence shifted in time series), that is, the number of base nucleic acid classifications (signed numbers) output from each register constituting the shift register 150. ).

The base pair generation unit 2 shifts one base from the both ends of the base sequence in the analysis range one by one in the center direction in the genome sequence input in parallel from the shift register 150, and r r from each end in the analysis range. Each base is combined corresponding to the positions from both ends (bases at symmetrical positions with a non-palinity base in between) to generate and output a preset base pair.
That is, the base pair generation unit 2 bases a combination of bases at positions opposite to each other (a symmetric position with a non-pain base) across the non-pain base (non-addition base) in FIG. As a pair, the data is output to a corresponding palindromic operation unit described later.
Hereinafter, a configuration example of the palindrome structure detection system in the genome sequence according to the present embodiment will be described with reference to the block diagram of FIG.

The palindromic operation unit 61 is an even palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 0, 3} as an analysis range. The first adding unit 3 ₆₁ includes three absolute value units 4 ₆₁ and one second adding unit 5 ₆₁ .
Each of the first addition units 3 ₆₁ performs addition of A _n−5 + A _n , A _n−4 + A _n−1 , and A _n−3 + A _n−2, and the corresponding absolute value unit 4 ₆₁ to each output.
Each of the absolute value units 4 ₆₁ outputs the absolute values S1 _n , S2 _n , S3 _n of the calculation results output from the corresponding first adder 3 ₆₁ .
The second adder 5 ₆₁ adds the absolute values S1 _n , S2 _n , S3 _n from each of the absolute value units 4 ₆₁ and outputs the addition result P1 _n . If the addition result P1 _n is “0”, it is detected that palindromic bases in the analysis range have palindromic structures.

The palindromic operation unit 62 is an odd palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 1, 3} as an analysis range. The first addition unit 3 ₆₂ includes three absolute value units 4 ₆₂ and one second addition unit 5 ₆₂ . Hereinafter, a palindromic operation unit with an odd number of non-palinity bases is an odd palindrome operation unit, and a palindrome operation unit with an even number of non-palinity bases is an even palindrome operation unit.
Each of the first addition units 3 ₆₂ performs addition of A _n−6 + A _n , A _n−5 + A _n−1 , and A _n−4 + A _n−2, and the corresponding absolute value unit 4 Each output to ₆₂ .
Each of the absolute value units 4 ₆₂ outputs the absolute values S1 _n−1 , S2 _n−1 , and S3 _n−1 of the operation results output from the corresponding first adder 3 ₆₂ .
The second addition unit _{5 62} adds the absolute value _{S1 n-1, S2 n-} 1, S3 n-1 from the absolute value unit _{4 62} respectively, and outputs the addition result _{P1 n-1.} If the addition result P1 _n-1 is “0”, it is detected that palindromic bases in the analysis range have a palindromic structure.

The palindromic operation unit 63 is an even palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 2, 3} as an analysis range. The first adding unit 3 ₆₃ includes four absolute value units 4 ₆₃ and two second adding units 5 ₆₃ .
Each of the first adding units 3 ₆₃ includes A _n−7 + A _n , A _n−6 + A _n−1 , A _n−5 + A _n−2 , and A _n−4 + A _n−3 . Addition is performed and output to the corresponding absolute value portion ₄₆₃ .
Each of the absolute value units 4 ₆₃ outputs the absolute values S1 _n−2 , S2 _n−2 , S3 _n−2 , and S4 _n−2 of the calculation result output from the corresponding first adder 3 ₆₃ .
Each of the second addition units 5 ₆₃ converts the absolute values S1 _n−2 , S2 _n−2 , and S3 _n−2 from the absolute value units 4 ₆₃ into absolute values S2 _n−2 , S3 _n−2 , and S4 _{n. -2} are added, and the addition result P1 _n-2 and the addition result P2 _n-2 are output.

If this addition result P1 _n−2 is “0”, the palindromic bases in the analysis range {palindromic base, non-palmographic base, palindromic base} = {3, 2, 3} have a palindromic structure. Is detected. If the addition result P2 _n−2 is “0”, the palindromic bases in the analysis range {pastogram base, non-pascal base, palindrome base} = {3, 0, 3} have the palindrome structure. Is detected.
Therefore, when both of the addition results P1 _n-2 and P2 _n-2 are “0”, the analysis is performed in the analysis range {palindromic base, non-palindromic base, palindromic base} = {3, 2, 3}. Since it was detected that the non-palindromic base that did not exist also becomes “0” as the addition result of A _n−4 + A _n−3 , the analysis range is finally set to 8 bases, and all the bases within the analysis range are palindrome. A base structure is detected.
As described above, the palindromic operation unit 63 performs base pairing with respect to the second addition unit corresponding to the minimum non-palindromic base number 0 even in the even number and the minimum non-palindromic base number 0 in the even number. And a second addition unit corresponding to the analysis range of the non-pain base number 2 increased by the unit, that is, the number of bases.

The palindromic operation unit 64 is an odd palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 3, 3} as an analysis range. The first adder unit 3 ₆₄ includes four absolute value units 4 ₆₄ and two second adder units 5 ₆₄ .
Each of the first addition units 3 ₆₄ includes A _n−8 + A _n , A _n−7 + A _n−1 , A _n−6 + A _n−2 , and A _n−5 + A _n−3 . Addition is performed and output to the corresponding absolute value portion ₄₆₄ .
Each of the absolute value units 4 ₆₄ outputs the absolute values S1 _n−3 , S2 _n−3 , S3 _n−3 , and S4 _n−3 of the operation result output from the corresponding first adder 3 ₆₄ .
Each of the second addition units 5 ₆₄ converts the absolute values S1 _n−3 , S2 _n−3 , and S3 _n−3 from the absolute value units 4 ₆₄ into the absolute values S2 _n−3 , S3 _n−3 , and S4 _{n. -3} is added, and the addition result P1 _n-3 and the addition result P2 _n-3 are output.

If this addition result P1 _n-3 is “0”, the palindromic bases in the analysis range {palindromic base, non-pastronomic base, palindromic base} = {3, 3, 3} have a palindromic structure. Is detected. Also, if the addition result P2 _n-3 is “0”, the palindromic bases in the analysis range {palindromic base, non-palatomic base, palindromic base} = {3, 1, 3} have a palindromic structure. Is detected.
Therefore, when both of the addition results P1 _n-3 and P2 _n-3 are “0”, the analysis is performed in the analysis range {palindromic base, non-palindromic base, palindromic base} = {3, 3, 3}. Since it was detected that the non-palindromic base that did not exist becomes “0” as the addition result of A _n−5 + A _n−3 , the analysis range is finally set to 9 bases and the central base _An−4 is excluded. Eight bases are detected to have a palindromic base structure.
As described above, the palindromic operation unit 64 performs base pairing with respect to the second addition unit corresponding to the smallest non-palindromic base number 1 at the odd number and the smallest non-palindromic base number 1 at the odd number. A second adding unit corresponding to the analysis range of the non-pain base number 3 increased in units, that is, the number of bases.
Moreover, it becomes possible to analyze the palindrome structure in the genome sequence by combining the results of the odd palindromic operation unit and the even palindromic operation unit described above.

  Also, in FIG. 3, in the configuration in FIG. 2 (b), the analysis range {palindromic base, non-palumal base, palindromic base} = {3, 4, 3}, analysis range {palindromic base, non Palindromic base, palindromic base} = {3,5,3}, analysis range {palindromic base, non-pastronomic base, palindromic base} = {3, 6, 3}, analysis range {palindromic base, non The palindromic base, palindromic base} = {3, 7, 3} is analyzed, and the palindrome structure having the base numbers of 10, 11, 12, 13 is substantially analyzed as the analysis range.

That is, the palindromic operation unit 65 is an even palindromic operation unit, and has a configuration corresponding to {palindromic base, non-palatomic base, palindromic base} = {3,4,3} as an analysis range, The first adder unit ₃₆₅ includes five first adder units ₃₆₅ , five absolute value units 4 ₆₅ , and three second adder units 5 ₆₅ .
Each of the first addition units 3 ₆₅ includes A _n−9 + A _n , A _n−8 + A _n−1 , A _n−7 + A _n−2 , A _n−6 + A _n−3 , A _{n−. 5} + A _n−4 is added and output to the corresponding absolute value portion ₄₆₅ .
The absolute value unit _{4 65} each, corresponding first adding unit ₃ is the operation result output from the ₆₅ absolute value _{S1 n-4, S2 n-} 4, S3 n-4, S4 n-4, S5 n-4 Is output.
Each of the second addition units 5 ₆₅ converts the absolute values S1 _n−4 , S2 _n−4 and S3 _n−4 from the absolute values 4 ₆₅ into absolute values S2 _n−4 , S3 _n−4 and S4 _{n−. 4} are added to absolute values S3 _n-4 , S4 _n-4 and S5 _n-4 , respectively, and an addition result P1 _n-4 , an addition result P2 _n-4 and an addition result P3 _n-4 are output.

If this addition result P1 _n-4 is “0”, the palindromic bases in the analysis range {pastigial base, non-pastronomic base, palindromic base} = {3,4,3} have a palindromic structure. Is detected. Also, if the addition result P2 _n-4 is “0”, the palindromic bases in the analysis range {pastedial base, non-palatomic base, palindromic base} = {3, 2, 3} have a palindromic structure. Is detected. Further, if the addition result P3 _n-4 is “0”, the palindromic bases in the analysis range {pastedial base, non-palatomic base, palindromic base} = {3, 0, 3} have a palindromic structure. Is detected.
Therefore, when all of the addition results P1 _n-4 , P2 _n-4, and P3 _n-4 are “0”, the analysis range {palindromic base, non-palindromic base, palindromic base} = {3,4, 3}, it is detected that the addition result of each of A _n−5 + A _n−4 and A _n−6 + A _n−3 is “0”. When the analysis range is 10 bases, it is detected that all bases within the analysis range have a palindromic base structure.
As described above, the palindromic operation unit 65 performs base pairing on the second addition unit corresponding to the smallest non-palindromic base number 0 even in the even number and the non-palindromic base number 0 smallest in the even number. There is a second addition unit corresponding to the analysis range of the non-pain base number 2 increased in units, that is, the number of bases, and the analysis range of the non-pain base number 4 increased in number of bases. doing.

The palindromic operation unit 66 is an odd palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 5, 3} as an analysis range. The first adding unit 3 ₆₆ includes five absolute value units 4 ₆₆ and three second adding units 5 ₆₆ .
Each of the first addition units 3 ₆₆ includes A _n−10 + A _n , A _n−9 + A _n−1 , A _n−8 + A _n−2 , A _n−7 + A _n−3 , _An Each of _-6 + A _n-4 is added and output to the corresponding absolute value portion ₄₆₆ .
Each of the absolute value units 4 ₆₆ is the absolute value S1 _n-5 , S2 _n-5 , S3 _n-5 , S4 _n-5 , S5 _{n-5 of the} operation result output from the corresponding first adder 3 _66. Is output.
Each of the second adders 5 ₆₆ converts the absolute values S1 _n-5 , S2 _n-5 , S3 _n-5 from the absolute values 4 ₆₆ into the absolute values S2 _n-5 , S3 _n-5 , S4 _{n- 5} , absolute values S3 _n-5 , S4 _n-5 , S5 _n-5 are added, respectively, and an addition result P1 _n-5 , an addition result P2 _n-5 , and an addition result P3 _n-5 are output.

If this addition result P1 _n-5 is “0”, the palindromic bases in the analysis range {pastigial base, non-palatomic base, palindromic base} = {3, 5, 3} have a palindromic structure. Is detected. Further, if the addition result P2 _n-5 is “0”, the palindromic bases in the analysis range {palindromic base, non-pastronomic base, palindromic base} = {3, 3, 3} have the palindrome structure. Is detected. Also, if the addition result P3 _n-5 is “0”, the palindromic bases in the analysis range {palindromic base, non palindromic base, palindromic base} = {3, 1, 3} have a palindromic structure. Is detected.
Therefore, when all of the addition results P1 _n-5 , P2 _n-5 and P3 _n-5 are “0”, the analysis range {palindromic base, non-palindromic base, palindromic base} = {3, 5, 3}, it is detected that the addition result of both A _n−6 + A _n−4 and A _n−7 + A _n−3 is “0”. The analysis range is 11 bases, and it is detected that 10 bases except the central base _An-5 have a palindromic base structure.
Furthermore, by increasing the palindromic operation unit 67 that is an even palindromic operation unit and the number operation unit 68 that is an odd-numbered operation unit, a palindrome structure having any number of bases can be detected. It can be performed.

<Second Embodiment>
Next, the palindrome structure detection system in the genome sequence according to the second embodiment of the present invention will be described with reference to FIG. FIG. 4 is a block diagram showing an operation of detecting a palindrome structure in an analysis range with an even number of bases in the genome sequence according to the second embodiment. In the second embodiment of FIG. 4, the same components as those of the first embodiment of FIG.
In the first embodiment, when the analysis range is small, the palindrome structure can be analyzed at high speed. However, as the analysis range becomes wider, the number of adders increases as shown in FIG. It is expected to go.
However, as shown in FIG. 5, when the results in FIG. 2 are viewed with t = n at the time of reading to the base An in the genome sequence, the same analysis range (same bases) is obtained at t = n−1. It can be seen that the detection process is being performed for the numerical analysis range.

In other words, the same processing is performed as the addition processing only by the position where the palindrome is detected in the genome sequence is shifted by one base and the time for reading the base in the genome sequence is shifted.
Therefore, in consideration of the temporal transition of the genome sequence, the addition structure in the first embodiment of FIG. 2 can be configured with the addition structure according to the second embodiment shown in FIG. Similarly, for palindromic structures with 3 or more bases). Of course, a palindrome structure having a larger number of bases can be expressed by the same addition structure.

In the configuration of FIG. 4, the palindromic operation unit 70 is an even palindromic operation unit, and corresponds to {pastolic base, non-palindromic base, palindromic base} = {3, 0, 3} as an analysis range. The configuration includes three first adder units ₃₇₀ , three absolute value units ₄₇₀ , and one second adder unit ₅₇₀ .
Each of the first addition units 3 ₇₀ performs addition of A _n−5 + A _n , A _n−4 + A _n−1 , and A _n−3 + A _n−2, and the corresponding absolute value unit 4 Output to ₇₀ .
The absolute value unit _{4 70} each of which outputs the absolute value _{S1 n,} S2 _n, S3 n of the operation result output from the corresponding first adder _{3 70.}
Second adding unit _{5 70} respectively adds the absolute value _{S1 n,} S2 _n, S3 n from the absolute value unit _{4 70} respectively, and outputs each sum P1 _n.

The palindromic operation unit 71 is an odd palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 1, 3} as an analysis range. The first adding unit 3 ₇₁ includes three absolute value units 4 ₇₁ and one second adding unit 5 ₇₁ .
Each of the first addition units 3 ₇₁ performs addition of A _n−6 + A _n , A _n−5 + A _n−1 , and A _n−4 + A _n−2, and the corresponding absolute value unit 4 _{To 71} .
Each of the absolute value units 4 ₇₁ outputs the absolute values S1 _n−1 , S2 _n−1 , S3 _n−1 of the calculation results output from the corresponding first adder 3 ₇₁ .
Each of the second addition units 5 ₇₁ adds the absolute values S1 _n−1 , S2 _n−1 , S3 _n−1 from each of the absolute value units 4 ₇₁ and outputs an addition result P1 _n−1 .

The palindromic operation unit 72 is an even palindromic operation unit, and has a configuration corresponding to {pastolic base, non-pastronomic base, palindromic base} = {3, 2, 3} as an analysis range. The first addition unit 3 ₇₂ , the three absolute value units 4 _72, and the second addition unit 5 ₇₂ are configured.
Each of the first addition units 3 ₇₂ adds each of A _n−7 + A _n , A _n−6 + A _n−1 , and A _n−5 + A _n−2, and the corresponding absolute value unit 4 ₇₂ .
Each of the absolute value units 4 ₇₂ outputs the absolute values S1 _n−2 , S2 _n−2 , and S3 _n−2 of the calculation results output from the corresponding first adder 3 ₇₂ .
Each of the second addition units 5 ₇₂ adds the absolute values S1 _n−2 , S2 _n−2 , and S3 _n−2 from each of the absolute value units 4 ₇₂ and outputs an addition result P1 _n−2 respectively.

The palindromic operation unit 73 is an odd palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 3, 3} as an analysis range. The first adding unit 3 ₇₃ includes three absolute value units 4 ₇₃ and one second adding unit 5 ₇₃ .
Each of the first addition units 3 ₇₃ performs addition of A _n−8 + A _n , A _n−7 + A _n−1 , and A _n−6 + A _n−2, and the corresponding absolute value unit 4 _{To 73} .
Each of the absolute value units 4 ₇₃ outputs the absolute values S1 _n−3 , S2 _n−3 , and S3 _n−3 of the calculation result output from the corresponding first adder 3 ₇₃ .
Each of the second addition units 5 ₇₃ adds the absolute values S1 _n-3 , S2 _n-3 , S3 _n-3 from each of the absolute value units 4 ₇₃ and outputs an addition result P1 _n-3 .

In the present invention, as shown in FIG. 6, each palindromic operation unit 74 (even number palindrome operation unit), 75 (odd palindrome operation unit), and 76 (even number palindrome operation unit) which are larger analysis ranges. And 77 (odd palindromic operation unit) can also be constituted by three first addition units 3, three absolute value units 4 and one second addition unit 5 shown in FIG.
In FIG. 7 described above, a unit consisting of three first adders, an absolute value portion that takes the absolute value of the calculation result of each first adder, and a second adder that is output from the absolute value portion is provided. Assuming a palindromic calculation unit, for example, a palindrome structure with an analysis range (number of bases m) of 6 bases or 7 bases is to extract a pair structure of 3 bases. Or, 9 bases can provide two palindromic operation units, and n bases can be calculated by r palindromic operation units such that r = F ((n−4) / 2). Here, F () is a function that outputs an integer value obtained by rounding down the calculation result in ().

However, the palindrome unit only represents a palindrome structure of 3 bases, and a palindrome structure of 4 bases or more cannot be detected.
In order to detect the palindrome structure of 4 bases or more, it is the case when t = n, t = n−1, t = n−2,. It is necessary to become.
That is, {pastolic base, non-pastronomic base, palindromic base} = {3, 0, 3} of palindromic operation unit 70 and {pascalial base, non-pascal base, palindrome of palindromic operation unit 72 As shown in FIG. 8, when the base} = {3, 2, 3}, the palindromic operation unit 72 is “0” at the time t = n, and immediately before that, that is, t = n one base before. When the palindrome calculation unit 70 is “0” at the time of −1, the palindrome structure {3, 0, 3} output from the palindrome calculation unit 70 and the palindrome structure {3, 2 and 3} are combined to form four base pairs of {palindromic base, non-palindromic base, palindromic base} = {4, 0, 4}, as in the first embodiment. The presence of a palindrome structure is detected.

Next, the operation of the palindrome structure detection system in the genome sequence according to the second embodiment will be described with reference to FIGS. 9, 10 and 11. FIG. FIG. 9 is a conceptual diagram showing the entire palindrome structure pattern generation showing the operation of the palindrome structure system. 10 is an enlarged view of region A in FIG. 9, and FIG. 11 is an enlarged view of region B in FIG. FIG. 9 is a conceptual diagram relating to palindrome structure pattern generation showing the result of detecting the palindrome structure in the analysis range where the number of bases calculated by the odd palindrome calculation unit is odd.
9 and 14 for explaining the palindrome structure pattern generation in the following description, the display unit (not shown) displays the detection result of the palindrome structure detection system as an analysis result diagram.
The leftmost column is the position number indicating the order from the top of the base sequence in the genome (DNA) sequence (the base sequence starts from the base number of the base sequence output from the base / number converter 1) No. indicating whether or not a nucleobase name and a partially significant codon name corresponding to each number are described in the next two columns. There are four columns in the column of the number of nucleic acid classifications (signed numbers), and all the columns are the same, and each base in the left column is converted by the base / number conversion unit 1 with a sign. Numbers (number of nucleic acid classifications) are described. Here, each column of the number of nucleic acid classifications (signed numbers) corresponds to the type of palindrome structure to be detected, and surrounds the number of nucleic acid classifications in the palindrome structure and the detected base sequence region, or the color It is used to visually indicate which region has a palindrome structure by marking such as changing.
That is, from the column on the left side of FIG. 9, the base names of A, T, G, and C and the signed numbers of +1, −1, +2, and −2 corresponding to the base names A, T, G, and C are shown. It is shown.

Each of the first addition units 3 ₇₁ in the palindromic operation unit 71 adds to the columns of S1, S2 and S3 below the next palindrome structure {3, 1, 3}, and the absolute value unit 4 ₇₁ The outputs of the absolute values S1 _n−1 , S2 _n−1 , S3 _{n−1 obtained} by converting the addition result into absolute values are shown.
Further, the P1 section of the bottom of the palindrome {3,1,3}, the second adding unit _{5 71} obtained by adding the absolute value _{S1 n-1, S2 n-} 1, S3 n-1 each Results for P1 _n-1 are listed.
Similarly, the column of S1, S2 and S3 at the bottom of the next palindrome {3,3,3}, the first adding unit _{3 73,} each adding each of the palindromic calculation unit 73, the absolute value part _{4 73} is the sum of the absolute value by the absolute value _{S1 n-3, S2 n-} 3, S3 n-3 outputs of each are shown.
In addition, in the column of P1 below the palindrome structure {3, 3, 3}, the second addition unit ₅₇₃ adds the absolute values S1 _n−3 , S2 _n−3 , and S3 _n−3 respectively. Results for P1 _n-3 are listed.

Then, the column of S1, S2 and S3 at the bottom of the next palindrome {3,5,3}, the first adding unit _{3 75,} each adding each of the palindromic calculation unit 75, the absolute value unit Reference numeral 4 ₇₅ shows outputs of absolute values S1 _n-5 , S2 _n-5 , and S3 _{n-5 obtained} by converting the addition result into absolute values.
Further, in the column of P1 at the bottom of the palindrome {3,5,3}, the second adding unit _{5 75} obtained by adding the absolute value _{S1 n-5, S2 n-} 5, S3 n-5 each Results for P1 _n-5 are listed.
Similarly, each of the first addition units 3 ₇₇ in the palindromic operation unit 77 adds to the columns of S1, S2, and S3 below the next palindrome structure {3, 7, 3}, and the absolute value part _{4 77} is the sum of the absolute value by the absolute value _{S1 n-7, S2 n-} 7, S3 n-7 outputs of each are shown.
Further, in the column of P1 at the bottom of the palindrome {3,7,3}, the second adding unit _{5 77} obtained by adding the absolute value _{S1 n-7, S2 n-} 7, S3 n-7 each Results for P1 _n-7 are listed.

Thereafter, similarly, the palindromic operation unit 79 for analyzing the palindrome structure {3, 9, 3}, the palindromic operation unit 711 for analyzing the palindrome structure {3, 11, 3}, the palindrome structure {3, 13 and 3}, and the results of the palindromic operation unit 715 that analyzes the palindrome structure {3, 15, 3} are described.
In addition, the column corresponding to each analysis range in which the q value of each analysis range at the right end is described is rearranged so that each analysis result P1 is aligned by shifting the base sequence one by one.
q (q = 15 in the table) from the left q0 = qmax−2 · 0 = 15−2 · 0 = 15
q1 = qmax−2 · 1 = 15−2 · 1 = 13
q2 = qmax−2 · 2 = 15−2 · 2 = 11
q3 = qmax−2 · 3 = 15−2 · 3 = 9
q4 = qmax−2 · 4 = 15−2 · 4 = 7
:
:
qn = qmax-2 · n = 15-2 · n
Since “= 0” exists in n = 0 and n = 4 in the lower area of the character string “understand palindromic structure from diagonal lines”,
n = 0: palindrome structure around the current location {3, 15, 3}
n = 4: Palindrome structure {3, 7, 3} around the current location
It can be seen that this structure.
Also, when “0” exists in consecutive odd numbers or even numbers, such as n = 4: palindrome structure {3, 7, 3}, n = 5: palindrome structure {3, 5, 3}, The palindrome structure of the palindrome structure {4, 5, 4} is detected at the fourth center.
From this result, it is possible to easily detect what palindromic structure the DNA has.
In the example of FIG. 9, in the 42nd pattern, the analysis range of the palindromic operation unit 715 corresponding to {palindromic base, non palindromic base, palindromic base} = {3, 15, 3} is the palindrome. The detection result having the structure, that is, P1 _n-15 = 0. In addition, the analysis range of the palindromic operation unit 77 corresponding to {palindromic base, non-pastronomic base, palindromic base} = {3, 7, 3} in the 38th pattern 4 bases before this is The detection result having the sentence structure, that is, P1 _n-7 = 0.
The palindrome pattern synthesis unit not shown in the figure combines the detection results of the analysis range in which the palindrome structure is detected in the result calculated by shifting one base at a time. It is possible to detect palindrome structures in many analysis ranges.
For example, in the example of FIG. 9, P1 _n−7 = 0 in the 38th pattern and P1 _n−15 = 0 in the 42nd pattern. Detects a palindrome structure with two 3 base pairs as shown in FIG.

In the example of FIG. 9, the analysis range of the palindromic operation unit 77 corresponding to {palindromic base, non palindromic base, palindromic base} = {3, 7, 3} in the 50th pattern is The detection result having the palindrome structure, that is, P1 _n-7 = 0. In addition, in the 49th pattern one base before this, the analysis range of the palindromic operation unit 75 corresponding to {palindromic base, non-palatomic base, palindromic base} = {3, 5, 3} is The detection result having the sentence structure, that is, P1 _n-5 = 0.
As described above, the palindrome pattern synthesis unit not shown in the figure detects the palindrome structure by combining the detection results of the analysis range in which the palindrome structure is detected in the result calculated by shifting one base at a time. The palindrome structure in the analysis range with the largest number of bases can be detected.
For example, in the example of FIG. 9, P1 _n-5 = 0 in the 49th pattern and P1 _n-7 = 0 in the 50th pattern. Detects a palindrome structure with 13 bases and one 4-base pair as shown in FIG.

In order to detect whether or not the diagonal line Z in FIG. 9 can be synthesized with the previous base, whether or not P1 = 0 at the position of the base number in the genome sequence in each analysis range by the palindromic pattern synthesis unit. This shows the scanning order for detecting these. Then, in the detection process of scanning the diagonal line Z, the palindrome pattern synthesis unit synthesizes the calculation results of the palindrome calculation unit one base before the analysis result of each of the palindrome calculation units with two smaller analysis ranges. By processing, it is possible to synthesize the analysis range where the base number of the central part matches, and as described above, detect and output the palindrome structure of the base in the largest analysis range where the palindrome structure is detected To do.
As described above, in FIGS. 9, 10, and 11, base names are given the same numbers to the base pairs that form base pairs in the stem-loop structure, and the bases that are in a complementary relationship have different polarities. By attaching a sign, the user can see the palindrome pattern visually and visually, without seeing the base name and its complementary relationship, by looking at the signed number pattern. It turns out that the operation to detect becomes easy.

Although FIG. 9 describes the analysis in the analysis range of the odd base number by the odd palindromic operation unit, the analysis in the analysis range of the even base number can be performed in the same manner.
Next, the operation of the palindrome structure detection system in the genome sequence according to the second embodiment will be described with reference to FIGS. 14, 15 and 16. FIG. 14 is a conceptual diagram showing the entire palindrome structure pattern generation showing the operation of detecting the palindrome structure in the analysis range where the number of bases of the palindrome structure system is an even number. 15 is an enlarged view of region A in FIG. 14, and FIG. 16 is an enlarged view of region B in FIG. FIG. 14 is a conceptual diagram relating to palindrome structure pattern generation showing the result of detecting the palindrome structure in the analysis range of the even number of bases calculated by the even palindrome calculation unit.
In FIG. 14, as in FIG. 9, the leftmost column indicates the order of bases in the genome sequence, and the next two columns describe the nucleobase names corresponding to the respective numbers and partially significant codon names. Has been. The column of the number of nucleic acid classification (number with a sign) is the same in any column, and the number with a sign (number of nucleic acid classification) in which each base in the left column is converted by the base / number conversion unit 1 is described. . That is, from the left corner of FIG. 14, the base name of ATGC and the numbers with signs of +1, −1, +2, and −2 corresponding to this base name ATGC are shown.

In the column of the next palindrome S1 at the bottom of the structure {3,0,3}, S2 and S3, first adding unit _{3 70,} each adding each of the palindromic calculation unit 70, the absolute value unit _{4 70} The outputs of the absolute values S1 _n , S2 _n and S3 _{n obtained} by converting the addition result into absolute values are shown.
Further, in the column of P1 at the bottom of the palindrome {3,0,3}, the second adding unit _{5 70} absolute value _{S1 n,} S2 _n, S3 n each obtained by adding P1 _n results described Has been.
Similarly, the column of a certain S1, S2 and S3 at the bottom of the next palindrome {3,2,3}, the first adding unit _{3 72,} each adding each of the palindromic calculation unit 72, the absolute value part _{4 72} is the sum of the absolute value by the absolute value _{S1 n-2, S2 n-} 2, S3 n-2 output of each is shown.
Further, in the column of P1 at the bottom of the palindrome {3,2,3}, the second adding unit _{5 72} adds the absolute value _{S1 n-2, S2 n-} 2, S3 n-2 , respectively Results for P1 _n-2 are listed.

Then, in the column of a S1, S2 and S3 at the bottom of the next palindrome {3,4,3}, the first adding unit _{3 74,} each adding each of the palindromic calculation unit 74, the absolute value unit 4 ₇₄ is the sum of the absolute value by the absolute value _{S1 n-4, S2 n-} 4, S3 n-4 outputs of each are shown.
Further, the P1 section of the bottom of the palindrome {3,4,3}, the second adding unit _{5 74} adds the absolute value _{S1 n-4, S2 n-} 4, S3 n-4 , respectively P1 _n-4 results are listed.
Similarly, the column of S1, S2 and S3 at the bottom of the next palindrome {3,6,3}, the first adding unit _{3 76,} each adding each of the palindromic calculation unit 76, the absolute value part _{4 76} is the sum of the absolute value by the absolute value _{S1 n-6, S2 n-} 6, S3 n-6 output of each is shown.
Further, the P1 section of the bottom of the palindrome {3,6,3}, the second adding unit _{5 76} adds the absolute value _{S1 n-6, S2 n-} 6, S3 n-6 , respectively Results for P1 _n-6 are listed.

Thereafter, similarly, the palindromic operation unit 78 that analyzes the palindrome structure {3, 8, 3}, the palindrome operation unit 710 that analyzes the palindrome structure {3, 10, 3}, the palindrome structure {3, 12 and 3}, and the results of the palindrome operation unit 714 that analyzes the palindrome structure {3, 14, 3} are described.
In the example of FIG. 14, in the 39th pattern, the analysis range of the palindromic operation unit 74 corresponding to {palindromic base, non palindromic base, palindromic base} = {3,4,3} is the palindrome. The detection result having the structure, that is, P1 _n-4 = 0.

In addition, in the 50th pattern, a detection result in which the analysis range of the palindromic operation unit 78 corresponding to {palindromic base, non palindromic base, palindromic base} = {3, 8, 3} has a palindromic structure That is, P1n-8 = 0.
The palindrome pattern synthesizer (not shown) detects the analysis range in which the palindrome structure is detected in the result calculated by shifting one base at a time, as in the case where the analysis range already described is an odd number of bases. By combining the results, the palindrome structure in the analysis range with the largest number of bases in which the palindrome structure is detected can be detected.
For example, in the example of FIG. 14, since P1 _n-4 = 0 in the 39th pattern, the palindrome pattern synthesis unit has an analysis range of 10 bases as shown in FIG. A palindrome structure with one base pair is detected.
In addition, since P1 _n-8 = 0 in the 50th pattern, the palindromic pattern synthesis unit has an analysis range of 14 bases and one 3 base pair as shown in FIG. 13B. Detect a palindrome structure.

As described above, in the same manner as in FIGS. 9, 10, and 11, the base names are the same in FIGS. 14, 15, and 16, and the same numbers are assigned to the base pairs that form the base pairs in the stem-loop structure. It can be seen that by adding signs having different polarities between the bases in FIG. 4, the palindrome pattern can be visually confirmed, and the operation for detecting the palindrome structure becomes easy.
In addition, the diagonal line Z in FIG. 14 indicates whether or not the palindromic pattern synthesizer can analyze the base number position in the genome sequence in each analysis range in order to detect whether or not it can be synthesized with the previous base as in FIG. The scanning order for detecting whether or not P1 = 0 is shown. Then, in the detection process of scanning the diagonal line Z, the palindrome pattern synthesis unit synthesizes the calculation results of the palindrome calculation unit one base before the analysis result of each of the palindrome calculation units with two smaller analysis ranges. By processing, it is possible to synthesize the analysis range where the base number of the central part matches, and as described above, detect and output the palindrome structure of the base in the largest analysis range where the palindrome structure is detected To do.

Then, the palindrome pattern synthesis unit detects and outputs the palindrome structure in the genome sequence by the combination in the even and odd analysis ranges described above.
The palindrome pattern synthesis unit can easily detect the position of the palindrome structure by detecting the position of the analysis range where the palindrome structure is detected by the number indicating the base order in the genome sequence. can do.
That is, the palindrome pattern synthesis unit detects the presence or absence of the palindrome structure in the analysis range with the number corresponding to the last base of the analysis range in the direction in which the analysis of the palindrome structure in the genome sequence proceeds, By sequentially entering the result P1 of the second adder circuit in the number, the result of the presence or absence of the palindrome structure corresponding to each analysis range is entered. It can be easily confirmed at which position in the genome sequence the analysis range having the number of bases is present.

<Hardware construction of palindrome structure detection system>
The configuration as described above can realize the calculation function of the spreadsheet software in the personal computer as each function described above. However, since the DNA genome sequence is a huge base sequence, a large amount of base sequence data can be obtained. In order to analyze at high speed, it is conceivable to perform analysis with hardware using a simple circuit.
For this reason, the circuit shown in FIG. 17 (16 base bases) includes a first addition circuit that adds signed numbers corresponding to two bases and an absolute value part that converts the addition result into an absolute value as one arithmetic unit. The palindrome structure in the DNA sequence is detected in the sequence unit. For example, corresponding to the first embodiment, the palindrome structure {3, 0, 3} having three base pairs to the palindrome structure {3, 10, 3} circuit configured to detect the palindrome structure.

Here, since the number with a sign is a binary bit unit operation, each of the bases A, G, C, and T (U) is represented by a binary number as [sign, most significant bit, least significant bit]. Represent. Here, for example, the sign is “0” for “+” and “1” for “−”.
Therefore, since the base A is “+1”, it is expressed as [sign, most significant bit (21), least significant bit (20)] = [0, 0, 1], and the base T (U) is “−1”. Therefore, [sign, most significant bit, least significant bit] = [1, 0, 1] and base G is “+2”, so [sign bit, most significant bit, least significant bit] = [0, 1, 0], and the base T (U) is “−2”, so [sign bit, most significant bit, least significant bit] = [1, 1, 0]. .
Data conversion into binary numbers for each base is performed by the base / number conversion unit 1 described above.

  Therefore, as shown in the circuit diagram of FIG. 17, the arithmetic unit calculates each bit in [sign bit, most significant bit, least significant bit] which is a bit string indicating a signed number corresponding to each of the two bases. Therefore, EXNOR101 for calculating the sign, EXOR102 for calculating the most significant bit (second bit), EXOR103 for calculating the least significant bit (first bit), and the results of EXNOR101, EXOR102, and EXOR103 The OR 104 calculates whether or not the calculated bases are complementary.

Thereby, for example, in FIG. 17, the absolute value S as a result of adding the signed number corresponding to the base An _-5 and the signed number corresponding to the base An is obtained as “0” or “1”. .
As an example, the base _An-5 is “−2 (base C)”, and the signed numeric value expressed in binary number is [sign bit, most significant bit, least significant bit] = [1, 1, 0]. When the base An is “+2 (base G)”, the signed numerical value represented by the binary number is [sign bit, most significant bit, least significant bit] = [0, 1, 0].
In this case, since the least significant bit is the same between “0” and “0”, the EXOR 103 outputs “0”, and since the most significant bit is the same between “1” and “1”, the EXOR 102 is “0”. , And the sign bit differs between “1” and “0”, so the EXNOR 101 outputs “0”.
Then, since all the input data is “0”, the OR 104 outputs the resulting absolute value S as “0”. Thereby, it is detected that the base _An-5 and the base _An are bases in a complementary relationship forming a base pair in the stem loop structure.

In addition, base _An-5 is “+2 (base G)”, and a signed numerical value represented by a binary number is [sign bit, most significant bit, least significant bit] = [0, 1, 0] If it is similarly is a _n "+2 (base G)", signed numerical values shown in binary is a [sign bit, the most significant bit, the least significant bit] = [0,1,0].
In this case, since the least significant bit is the same between “0” and “0”, the EXOR 103 outputs “0”, and since the most significant bit is the same between “1” and “1”, the EXOR 102 is “0”. Since the sign bit is the same between “0” and “0”, the EXNOR 101 outputs “1”.
Then, since “1” is included in the input data, the OR 104 outputs the resulting absolute value S as “1”. As a result, it is detected that the base _An-5 and the base _An are bases that are not in a complementary relationship that does not form a base pair in the stem loop structure.

In addition, base A _n-5 is “+1 (base A)”, and a signed numerical value represented by a binary number is [sign bit, most significant bit, least significant bit] = [0, 0, 1] _{If An} is “−2 (base C)”, the signed numerical value represented by a binary number is [sign bit, most significant bit, least significant bit] = [1, 1, 0].
In this case, since the least significant bit differs between “1” and “0”, EXOR103 outputs “1”, and since the most significant bit differs between “0” and “1”, EXOR102 changes “1”. Since the sign bit is different between “0” and “1”, the EXNOR 101 outputs “0”.
Then, since “1” is included in the input data, the OR 104 outputs the resulting absolute value S as “1”. As a result, it is detected that the base _An-5 and the base _An are bases that are not in a complementary relationship that does not form a base pair in the stem loop structure.

The palindromic calculation unit in FIG. 4 is configured as shown in FIG. 18 with three arithmetic units and an OR 200 corresponding to the second addition unit. This is a palindrome calculation unit that grasps the palindrome structure in which three or more bases are arranged.
FIG. 18 shows a configuration corresponding to the palindromic operation units 70, 72, 74, and 76 that are even palindromic operation units in FIG.
In each palindromic operation unit 70, 72, 74, 76, the palindrome structure {3, 0, 3}, palindrome structure {3, 2, 3}, palindrome structure {3, corresponding to the respective analysis range 4, 3} and signed numeric data corresponding to the bases in the palindromic structure {3, 6, 3} genome sequence are input.

As a result, each palindromic operation unit (70, 72, 74, 76) outputs "0" when the base pairs to be analyzed in the analysis range are all complementary, and any of them is not complementary “1” is output to the terminal.
That is, when all of the three arithmetic units 100 constituting the palindromic operation unit output “0”, the OR 200 outputs “0”, and the three arithmetic units 100 constituting the palindromic operation unit. OR 200 outputs “1” when any of the above outputs “1”.
In the above description, the palindrome calculation unit has been described as an even palindrome operation unit, but the odd palindrome operation unit has the same configuration.

Then, as described in the second embodiment, the time of the result calculated using this palindromic calculation unit, that is, the sequence number of the base in the genome sequence is shifted and written to the register, so that the rotation in each analysis range is performed. The sentence structure can be grasped.
The palindrome structure detection system according to the second embodiment realized by hardware will be described using the configuration example of the circuit block of FIG. The circuit block of FIG. 19 shows a palindromic structure detection portion when the number of non-palindromic bases is an even number. The configuration of the palindromic structure detection when the number of non-palindromic bases is an odd number in the same configuration as the circuit block of FIG. By combining them, the palindrome structure detection system according to the present embodiment is configured.

In FIG. 19, in the data input shift register, the base / number conversion unit 1 sets signed numeric data [sign bit, most significant bit, least significant bit] corresponding to the genome sequence for each base in units of 3 bits. The data is sequentially transferred in the direction Q by the cycle T. At this time, each register of the data input shift register outputs signed data to be transferred to the palindromic computation unit.
A palindromic calculation unit (unit for calculating the addition result P1) is composed of a base pair generation unit 2 and a palindromic operation unit corresponding to each analysis range, and the signed data input at each cycle T. Based on the above, for each palindromic operation unit corresponding to the analysis range, the addition result P1 which is the analysis result is output to the palindrome register via the shift register group.
The shift register group includes shift registers provided between the output of each palindromic operation unit corresponding to each analysis range and the input of the palindrome register.
Each shift register in the shift register group synchronizes the 1-bit addition result P1 with the data transfer timing of the data input shift register every cycle T, and each time the number of bases in the analysis range decreases by two, the palindrome In order to match the analysis timing in the register, the number of stages is increased by one (to delay the timing).
In the example of FIG. 19, as the number of bases in the analysis range becomes 16, 14, 12, 10, 8, and 6, the number of registers in the shift register between the palindromic calculation unit group and the palindrome register is 0,1. , 2, 3, 4 and 5.

With the above-described configuration of the shift register group, each analysis range necessary for synthesizing each of the calculation results one base before the palindrome calculation unit with a small analysis range in each calculation result of each palindrome calculation unit Result P1 can be simultaneously output to the palindrome register, and an unillustrated palindrome pattern synthesizer refers to this palindrome register to sequentially synthesize analysis ranges having the same base number in the output center portion. As described in the explanation of the second embodiment, the palindrome structure of the base in the largest analysis range in which the palindrome structure is detected is detected and output.
For example, if the analysis range is 100 bases, as described above, a 100 base palindrome structure can be detected.
In this case, the palindrome structure is detected using the analysis range of the palindrome structure {pastront, non palindrome, palindrome} = {3, 94, 3}. A 100-stage shift register that performs bit transfer in parallel in bit units (sign bit, most significant bit, and least significant bit) is required.
Further, as the shift register group, the number of registers obtained by the following equation (1) is required.

The addition result P1 _n-94 is transferred to the palindrome register in the palindrome operation unit having the maximum value as the analysis range, that is, {pastoral, non palindrome, palindrome} = {3, ₉₄ , 3}. No shift register is required (shifting the base sequence in the genome sequence), and there are 48 palindromic operation units, so the number of registers in direction Q in FIG. 17 is 48 (= (94/2) +1), { Corresponding to the analysis range of palindrome, non palindrome, palindrome} = {3, 0, 3}, the longest number of stages in the shift register group inserted between the palindrome register and the palindrome operation unit Since the shift register has 47 stages, the number of registers in the shift register group can be calculated from the above equation (1).
Therefore, in a circuit for detecting a palindrome structure with 100 bases, 1128 (= 48 × 47) registers are required.
Further, since the palindrome register corresponds to 48 palindromic operation units, that is, it is necessary to store 48 addition results (P1 _n , P1 _n-2 ,...), 48 registers Is required.

In order to correspond to the even palindromic operation unit and the odd palindromic operation unit, twice the number of registers and the number of palindromic operation units described above are required. Can be made into one chip.
If the palindromic calculation unit can calculate the period T, that is, within one clock period, the data input shift register under the palindromic calculation unit needs to shift data 100. The palindrome structure can be grasped by 147 clocks of 47 clocks for the maximum length shift register (47 stages) in the shift register group.
Then, if the number of bases in the human genome sequence is 3 billion, in order to know the palindrome structure up to 100 bases, it can be processed in 3 billion +147 clocks.
Here, it is assumed that 147 is a small number substantially equal to “0” compared to 3 billion, and is operated at 100 MHz.
3.0 × 109 / (100 × 106) = 30 (s)
It can be seen that can be processed by.

<Third Embodiment>
Further, it has been found that a restriction enzyme is naturally present as a very remarkable substance frequently used in a technique called recombinant DNA experimental technique or genetic engineering developed in recent years. This restriction enzyme has the property of recognizing the DNA of a living organism other than itself and cleaving it at any location in a specific base sequence or at a specific location (for example, JP-A-10-262699). reference). Many of these restriction enzymes are present in bacteria and exist as a function for eliminating foreign DNA that invades the bacteria. Each of these restriction enzymes recognizes one type of short base sequence in DNA. The length of this recognized base sequence is usually 4 to 6 base pairs, and the base sequence of the cleavage site shows a palindromic structure (palindromic structure). By using this restriction enzyme, the molecular biologist opens the plasmid to make the foreign DNA into a form that can be inserted into the target DNA, eg, a plasmid.
Restriction enzymes are used as a means for cutting out necessary fragments from DNA molecules.
The discovery of plasmids and restriction enzymes has made it easier to clone DNA and obtain an exact copy of the desired DNA fragment. Therefore, a copy of the DNA fragment can be easily generated by isolating the fragment from DNA using restriction enzymes, inserting it into a plasmid, and introducing the hybrid plasmid into a host bacterium.

Here, a diagram showing the arrangement of the cleavage sites of each restriction enzyme in a DNA molecule is called a restriction enzyme cleavage map.
Moreover, the procedure for preparing the restriction enzyme cleavage map that has been conventionally performed is shown below.
First, the DNA that creates the restriction enzyme cleavage map is extracted as whole genome DNA from the tissue of the target organism, fragmented by physical methods, and used as a vector such as BAC (bacterial artificial chromosome) or YAC (yeast artificial chromosome). Cloning to create a genomic DNA library.
Next, several types of clones contained in the genomic DNA library are cleaved with a restriction enzyme, the position of the cleavage site on the clone is determined, and a restriction enzyme cleavage map in the clone is prepared. Then, restriction enzyme cleavage maps between the clones are compared, the cleavage pattern is analyzed, and adjacent clones are extracted (fingerprint method).
A group of clones that specify an adjacent relationship for a plurality of clones and cover an area of a certain length is called a contig. In parallel with this operation, the above-mentioned contig obtained is positioned on the chromosome of the genetic map with reference to the genetic map.

  When performing this positioning, use a marker that has sequence information of the base sequence among the markers to be positioned, create a PCR (Polymerase Chain Reaction) primer or hybridization probe based on the base sequence, A clone having the nucleotide sequence of the marker is identified from the clones in the middle. If one of the clones contained in a certain contig is positioned on the chromosome in this way, the position of the contig itself on the chromosome is also revealed. If a clone as a contig can be located almost throughout the chromosome by repeating the above operations, a restriction enzyme cleavage map as a physical map can be completed.

However, since genome information is read from DNA at high speed by the Sanger method or the like at present, it is very time-consuming to generate a restriction enzyme cleavage map by repeating the above-described experiment.
Here, since most of the cleavage sites in DNA are palindromic structures of 4, 5, 6 or 8 base pairs, the palindromic structure detection system in the genomic sequence in the first embodiment can be used to perform faster round-trips. By searching for the base pair of the sentence structure, a restriction enzyme cleavage map showing the restriction enzyme cleavage site can be easily generated. Hereinafter, a palindrome structure detection system for generating a restriction enzyme cleavage map will be described.

Hereinafter, a palindrome structure detection system in a genome sequence according to the third embodiment of the present invention will be described with reference to FIG. FIG. 22 is a block diagram illustrating a configuration example of the palindrome structure detection system in the genome sequence according to the present embodiment.
In the present embodiment, the analysis range of the palindrome structure is set to a non-palindrome q (= 0) base, that is, there is no non-palindrome base in the palindrome structure, palindrome 2 (= r) base, palindrome 3 ( = R) As a structure composed of bases, the palindrome structure is detected while shifting the base sequence of the analysis range one base at a time, using the base sequence at the contrast position with respect to the center of the analysis range as a base pair.

As in the first embodiment, the base / number conversion unit 1 replaces each base in the genome sequence inputted by shifting one base at a time in time series with a number with a corresponding code, that is, base G Is converted to “+2”, base A is “+1”, base C is converted to “−2”, and base T is converted to “−1” and output.
For example, the shift register 150 sequentially adds the numbers with the signs inputted in time series from the base / number conversion unit 1 one by one in accordance with the timing at which the base / number conversion unit 1 outputs the numbers. Shift and output serially input numbers in parallel. The shift register 150 is configured to be able to shift by a number corresponding to the number of base sequences within the analysis range in the base pair generation unit 2 described later.

The base pair generation unit 2 shifts one base from the both ends of the base sequence in the analysis range one by one in the center direction in the genome sequence input in parallel from the shift register 150, and r r from each end in the analysis range. Each base is combined corresponding to the position from both ends (bases at symmetrical positions with a non-palinity base in between) to generate a preset base pair.
In other words, the base pair generation unit 2 uses a combination of bases at opposite positions (symmetric positions with a non-palinity base in between) across the center of the analysis range as base pairs, and the corresponding palindromic computation described later. Output to the section.

The palindromic operation unit 201 is an even palindromic operation unit, and has a configuration corresponding to {pastolic base, non-pastronomic base, palindromic base} = {2, 0, 2} as an analysis range. The first adding unit 3 ₆₁ includes three absolute value units 4 ₆₁ and one second adding unit 5 ₆₁ .
Each of the first addition units 3 ₆₁ performs the addition of A _n−3 + A _n and A _n−2 + A _n−1, and outputs each addition result to the corresponding absolute value unit 4 ₆₁ . .
Each of the absolute value units 4 ₆₁ outputs the absolute values S1 _n and S2 _n of the calculation results output from the corresponding first adder 3 ₆₁ .
The second addition unit 561 adds the absolute value _S1 n, S2 _n from the absolute value _{4 61} respectively, and outputs the addition result P1 _n. If the addition result P1 _n is “0”, it is detected that palindromic bases in the analysis range have palindromic structures.

The palindromic operation unit 202 is an even palindromic operation unit, and has a configuration corresponding to {pastolic base, non-palindromic base, palindromic base} = {3, 0, 3} as an analysis range. The first addition unit 3 ₆₂ includes three absolute value units 4 ₆₂ and one second addition unit 5 ₆₂ .
Each of the first addition units 3 ₆₂ performs addition of A _n−5 + A _n , A _n−4 + A _n−1 , and A _n−3 + A _n−2, and the corresponding absolute value unit 4 Each output to ₆₂ .
Each of the absolute value units 4 ₆₂ outputs the absolute values S1 _n−1 , S2 _n−1 , and S3 _n−1 of the operation results output from the corresponding first adder 3 ₆₂ .
The second addition unit _{5 62} adds the absolute value _{S1 n-1, S2 n-} 1, S3 n-1 from the absolute value _{4 62} respectively, and outputs the addition result _{P1 n-1.} If the addition result P1 _n-1 is “0”, it is detected that palindromic bases in the analysis range have a palindromic structure.

The database 500 stores information representing restriction enzymes having the palindrome structure as a cleavage site, corresponding to the type of base and the order of bases in the base sequence of the palindrome structure.
The search unit 501 outputs the palindrome structure {2} output by the shift register 150 when P1 _n is output as “0” in the cycle unit that the base / number conversion unit 1 converts the base into a number and outputs it. , 0, 2}, a restriction enzyme corresponding to the base sequence of _An , _An-1 , _An-2 , _An-3 was searched from the database 500, and P1 _n-1 was output as "0" In this case, the bases of A _n , A _n−1 , A _n−2 , A _n−3 , A _n−4 , and A _n−5 of the palindrome structure {3, 0, 3} output from the shift register 150. A restriction enzyme corresponding to the sequence is searched from the database 500. When the search is performed, the restriction enzyme is output together with the DNA base sequence number.
Here, the search unit 501 includes a base which is output from the A _n ~A _n-5 each shift register 150 information (the type and order of bases of bases in the base sequence of the palindromic), the addition result P1 and _n and P1 _n-1, the base from the beginning of the position number (base / numeric nucleotide sequence that is output from the conversion unit 1 showing the arrangement position in the DNA bases output from a _n of the shift register 150 from what number bases A number indicating whether the sequence has been started).

Next, the operation of the palindrome structure detection system in the genome sequence according to the third embodiment will be described with reference to FIG. FIG. 23 shows the palindrome structure pattern generation showing the operation of the palindrome structure system, the search for restriction enzymes having the base sequence as a cleavage site based on the detected base sequence of the palindrome structure, and the position of the palindrome structure in DNA FIG. 2 is a conceptual diagram for explaining the generation of a restriction enzyme cleavage map.
FIG. 23 for explaining the palindrome structure pattern generation in the following description displays the detection result of the palindrome structure detection system in which the display unit (not shown) has a restriction enzyme cut map generation function as an analysis result diagram.

  In FIG. 23, the leftmost column column indicates the order from the top of the base sequence in the genome sequence, and the nucleobase name corresponding to each number is described in the next column column. Here, there are two columns in the column of the number of nucleic acid classifications (signed numbers), and both columns have the same description (this column may be one column) and are adjacent by the base / number conversion unit 1. A signed number (number of nucleic acid classifications) in which each base in the column of the left column is converted is described. That is, as in FIG. 9, from the column of the left corner column, base names of A, T, G, and C, and +1, −1, +2, −, corresponding to the base names A, T, G, and C, A signed number of 2 (number of nucleic acid classifications) is shown. Here, each nucleic acid classification number (number with a sign) corresponds to the type of palindrome structure to be detected as in the first embodiment, and the palindrome structure and the region of the detected base sequence It is used to visually mark which region has a palindrome structure by marking such as changing the number of nucleic acid classifications or changing the color.

Below the palindrome structure {3, 0, 3}, there are columns of absolute values S1 _n−1 , S _n−1, and S3 _n−1. 3 ₅₁ each by adding the signed numeric output from the shift register 150, the absolute value unit _{4 61} absolute value _{S1 n-1} obtained by the absolute value of this _{sum, S2 n-1, S3 n} -1 each And an addition result P1 _n-1 column, and absolute values S1 _n-1 (| A _n + A _n-5 |), S2 _n-1 (| A _n-1 + A _n-4 |), S3 _n−1 (| A _n−2 + A _n−3 |) are added, and the numerical value of the addition result P1 _n−1 is shown.
At the bottom of the next palindrome {2,0,2}, has the column of the absolute value S1 _n and _{S n,} outputs the first adding section _{3 62} Each of the palindrome calculation unit 202 from the shift register 150 by adding the signed numbers is, the absolute value unit 4 ₆₂ output of the absolute value S1 _n, S2 _n each has an absolute value of this sum is shown, also has columns of the addition result P1 _n, absolute A numerical value of the addition result P1 _n obtained by adding the values S1 _n (| A _n + A _n−3 |) and S2 _n (| A _n−1 + A _n−2 |) is shown.

When the search unit 501 detects that the addition result P1 _n output from the palindromic calculation unit 201 or the addition result P1 _n−1 output from the palindromic calculation unit 202 is “0”, Whether a palindrome structure is detected is determined by detecting which one is “0”, and the corresponding configuration (palindrome structure {2, 0, 2} or palindrome structure {3, 0, 3}) The restriction enzyme corresponding to the base sequence detected as the palindrome structure is searched from the database 500 by the base type and the base arrangement order in the base sequence of each palindrome structure.
For example, since the base sequence {-1, -1, 1, 1} = {T, T, A, A} starting from the position number 14 has a palindrome structure, the palindromic operation unit 201 sets the addition result P1 _n to Output as “0”.
here,
_{S1 n = | A n + A} n-3 | = 0, S2 n = | A n-1 + A n-2 | = 0
And
P1 _n = S1 _n + S2 _n = 0 + 0 = 0
It becomes.

When the addition result P1 _n is input, the search unit 501 has the base of the palindrome structure {2, 0, 2} because the addition result P1 _n input from the palindromic operation unit 201 is “0”. A restriction enzyme corresponding to the sequence {-1, -1, 1, 1} is searched in the database 500.
At this time, the search unit 501 detects that the restriction enzyme corresponding to the base sequence {-1, -1, 1, 1} is not stored in the database 500, and as shown in FIG. In the column of the column of the number of nucleic acid classification (signed number) corresponding to 2, 0, 2}, mark the region portion of the base sequence {-1, -1, 1, 1} and “None” is displayed to notify that there is no restriction enzyme corresponding to this base sequence {-1, -1, 1, 1}.

On the other hand, since the base sequence {-2, -1, -1,1,1,2} = {C, T, T, A, A, G} starting from position number 15 has a palindrome structure, palindromic operations The unit 202 outputs the addition result P1 _n−1 as “0”.
here,
S1 _n-1 = | A _n + A _n-5 | = 0, S2 _n-1 = | A _n-1 + A _n-4 | = 0, S3 _n-1 = | A _n-2 + A _n-3 | = 0
And
P1 _n-1 = S1 _n-1 + S2 _n-1 + S3 _n-1 = 0 + 0 + 0 = 0
It becomes.

When the addition result P1 _n−1 is input, the search unit 501 has the palindrome structure {3, 0, 3 because the addition result P1 _n−1 input from the palindromic operation unit 201 is “0”. }, The database 500 is searched for a restriction enzyme corresponding to the base sequence {-2, -1, -1, 1, 1, 2}.
At this time, the search unit 501 detects that the restriction enzyme EcoRI corresponding to the base sequence {-2, -1, -1,1,1,2} is stored in the database 500, as shown in FIG. In addition, in the column of the column of the number of nucleic acid classifications (signed numbers) corresponding to the palindromic structure {3, 0, 3} with respect to the display unit (not shown), the base sequence {-2, -1, -1, 1 , 1, 2}, and the position corresponding to the first position number line of the palindromic base sequence (for example, the right-hand column where P1 _n-1 is displayed as “0”) The name of the detected restriction enzyme “EcoRI” is displayed, the restriction enzyme corresponding to this base sequence {−2, −1, −1,1,1,2} is “EcoRI”, and the restriction enzyme The position of the palindrome structure in the base sequence of the DNA at the cleavage site is notified. The position number may be displayed on the display unit together with the restriction enzyme name.

The palindromic operation unit 201 outputs the addition result P1 _n as “0” at the position number 24.
Then, since the addition result P1 _n input from the palindromic operation unit 201 is “0”, the search unit 501 has the base sequence {−2, −2, 2 which is the palindromic structure {2, 0, 2}. , 2} = {C, C, G, G}, the restriction enzyme corresponding to the database 500 is searched.
At this time, the search unit 501 detects that the restriction enzyme PalI corresponding to the base sequence {-2, -2, 2, 2} is stored in the database 500, and as shown in FIG. Mark the region part of the base sequence {-2, -2, 2, 2} in the column of the number of nucleic acid classifications (signed numbers) corresponding to the palindrome structure {2, 0, 2} In addition, the detected restriction enzyme name “PalI” is placed at the position corresponding to the line of the first position number of the palindromic structure base sequence (for example, the right adjacent column where P1 _n is displayed as “0”). The restriction enzyme corresponding to this base sequence {-2, -2, 2, 2} is "PalI", and the palindromic structure position in the DNA base sequence of the restriction enzyme cleavage site is notified. . The position number may be displayed on the display unit together with the restriction enzyme name.

As described above, in the palindrome structure detection system of the present embodiment, the region of the base sequence having the palindrome structure is detected from the DNA base sequence as in the first embodiment, and the detected palindrome structure The restriction enzyme corresponding to the base type and the base sequence in the base sequence is detected from the database 500 and output together with the position number indicating the position from the beginning in the base sequence of the DNA, whereby the base sequence of the DNA to be analyzed It has a function of generating a restriction enzyme cleavage map for.
In the present embodiment, a description has been given of a configuration that detects two types of palindrome structures, palindrome structure {2, 0, 2} and palindrome structure {3, 0, 3}.
In the palindrome structure as the base sequence of the restriction enzyme cleavage site, the palindrome structure {3, 0, 3} type occupies about 70% of the whole, and the palindrome structure {2, 0, 2 } Type base sequence is about 1.5% or more of the whole, so that the restriction enzyme cleavage map corresponding to the whole of 8.5% or more restriction enzyme cleavage sites in the palindromic structure detection system of this embodiment. Can be generated.

Further, in the restriction enzyme cleavage map, when the cleavage site is more detailed, by adding a configuration for detecting more types of palindrome structures using each palindrome calculation unit of the first embodiment, A restriction enzyme cleavage map showing restriction enzyme cleavage sites can be generated.
According to the palindrome structure detection system of the present embodiment, most of the cleavage sites by restriction enzymes in DNA are 4 base pairs (palindrome structure {2, 0, 2}), 5 base pairs (palindrome structure {2, 1). , 2}), 6 base pairs (palindrome structure {3, 0, 3}) or 8 base pairs (palindrome structure {4, 0, 4}). By using the palindrome structure detection system in the genome sequence in the embodiment, the base pair of the palindrome structure can be searched at high speed, and the restriction enzyme cleavage map showing the restriction enzyme cleavage site can be easily generated.

  The program describing the operation of each part for realizing the function of the palindromic structure detection system in FIG. 2, FIG. 4 and FIG. 22 was recorded on a computer-readable recording medium and recorded on this recording medium. Each process of palindromic structure detection (including creation of a restriction enzyme cleavage map) may be performed by causing the computer system to read and execute the program. Here, the “computer system” includes an OS and hardware such as peripheral devices. The “computer system” includes a WWW system having a homepage providing environment (or display environment). The “computer-readable recording medium” refers to a storage device such as a flexible medium, a magneto-optical disk, a portable medium such as a ROM and a CD-ROM, and a hard disk incorporated in a computer system. Further, the “computer-readable recording medium” refers to a volatile memory (RAM) in a computer system that becomes a server or a client when a program is transmitted via a network such as the Internet or a communication line such as a telephone line. In addition, those holding programs for a certain period of time are also included.

  The program may be transmitted from a computer system storing the program in a storage device or the like to another computer system via a transmission medium or by a transmission wave in the transmission medium. Here, the “transmission medium” for transmitting the program refers to a medium having a function of transmitting information, such as a network (communication network) such as the Internet or a communication line (communication line) such as a telephone line. The program may be for realizing a part of the functions described above. Furthermore, what can implement | achieve the function mentioned above in combination with the program already recorded on the computer system, what is called a difference file (difference program) may be sufficient.

It is a conceptual diagram used for description of a stem loop structure and a complementary base pair. It is a block diagram which shows the structural example of the palindrome structure detection system in the 1st Embodiment of this invention. It is a conceptual diagram explaining the structure of the palindrome structure calculating part corresponding to each analysis range in 1st Embodiment. It is a block diagram which shows the structural example of the palindrome structure detection system in the 2nd Embodiment of this invention. It is a conceptual diagram explaining the correspondence between the analysis range and the order of bases in the genome sequence in palindromic structure detection processing. It is a conceptual diagram explaining the structure of the palindrome structure calculating part corresponding to each analysis range in 2nd Embodiment. It is a block diagram which shows the structural example of the palindrome structure part (pain count calculation unit) in FIG. It is a conceptual diagram explaining the process which synthesize | combines two analysis ranges and detects the palindrome structure of more base numbers than the base number of palindrome by each palindrome structure part. It is a conceptual diagram which shows the whole palindrome structure pattern production | generation which shows the operation | movement corresponding to the odd palindrome structure part in the palindrome structure system in 2nd Embodiment. It is an enlarged view of the area | region A in FIG. FIG. 10 is an enlarged view of a region B in FIG. 9. It is a conceptual diagram explaining that a base pair is formed by complementary bases in a genome sequence, and a stem loop structure is formed. It is a conceptual diagram explaining that a base pair is formed by complementary bases in a genome sequence, and a stem loop structure is formed. It is a conceptual diagram which shows the whole palindrome structure pattern production | generation which shows the operation | movement corresponding to the even palindrome structure part in the palindrome structure system in 2nd Embodiment. It is an enlarged view of the area | region A in FIG. It is an enlarged view of the area | region B in FIG. It is a block diagram which shows the structural example of the arithmetic unit which has a function of the 1st addition part and the absolute value part provided corresponding to this 1st addition part. It is a block diagram which shows the structural example of an even number palindromic operation part using the arithmetic unit of FIG. It is a block diagram which shows the structural example of the part corresponding to the even palindrome structure detection part in the palindrome structure detection system by the 2nd Embodiment of this invention. It is a conceptual diagram explaining the palindrome structure which may produce | generate the stem loop structure in a genome arrangement | sequence. It is a conceptual diagram explaining the palindrome structure which may produce | generate the stem loop structure in a genome arrangement | sequence. It is a conceptual diagram explaining the structure of the palindrome structure calculating part corresponding to each analysis range in 3rd Embodiment. It is a conceptual diagram which shows the whole palindrome structure pattern production | generation which shows the operation | movement corresponding to the even palindrome structure part in the palindrome structure system to which the restriction enzyme cut | disconnection map creation function of 3rd Embodiment was added.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Base / number conversion part 2 ... Base pair production | generation part 3 ₆₁ , 3 ₆₂ , 3 ₆₃ , 3 ₆₄ , 3 ₆₅ , 3 ₆₆ , 3 ₆₇ , 3 ₆₈ ... 1st addition part 4 ₆₁ , 4 ₆₂ , 4 ₆₃ , 4 ₆₄ , 4 ₆₅ , 4 ₆₆ , 4 ₆₇ , 4 ₆₈ ... Absolute value parts 5 ₆₁ , 5 ₆₂ , 5 ₆₃ , 5 ₆₄ , 5 ₆₅ , 5 ₆₆ , 5 ₆₇ , 5 ₆₈ . 62, 63, 64, ₆₅ , ₆₆ , ₆₇ , ₆₈ ... palindromic operation units 3 ₇₀ , 3 ₇₁ , 3 ₇₂ , 3 ₇₃ , 3 ₇₄ , 3 ₇₅ , 3 ₇₆ , 3 ₇₇ ... First addition unit 4 ₇₀ , 4 ₇₁ , 4 ₇₂ , 4 ₇₃ , 4 ₇₄ , 4 ₇₅ , 4 ₇₆ , 4 ₇₇ ... absolute value part 500 ... database 501 ... search part 5 ₇₀ , 5 ₇₁ , 5 ₇₂ , 5 ₇₃ , 5 ₇₄ , 5 ₇₅ , 5 _76, 5 _{77 ...} the second adding section 70, 71, 72, 3, 74, 75, 76, 77, 201, 202 ... palindromic operation unit 100 ... operation unit 150 ... shift register 101 ... EXNOR (negative exclusive OR) 102, 103 ... EXOR (exclusive OR) 104, 200 ... OR (logical sum)

Claims (8)

Bases each forming a base pair with the genomic sequence Ategai the digits to a palindrome detection system for detecting a palindrome in the genome sequence,
For each base in the input genome sequence, assign the same number to the bases that form a complementary relationship in the genome sequence and attach a + sign to any one of the bases. , A base / number conversion unit that attaches a minus sign to the other base and replaces each of the bases with a number;
In the genome sequence, a base is shifted from the both ends in the analysis range one by one in the center direction, and n bases from each end in the analysis range are combined corresponding to the positions from both ends. a base pair generator for generating n base pairs;
N number of first addition units that independently add numbers corresponding to the bases of the base pairs output from the base pair generation unit, and outputs of the first addition units. the absolute value absolute value unit for calculating a, a palindromic calculation unit and a second adder for adding the absolute values of the addition result in the analysis range possess,
A palindrome structure detection system in a genome sequence , wherein when the second adder outputs 0, it is a detection signal that detects the presence of a palindrome structure with the n base pairs . The palindrome structure detection system in the genome sequence according to claim 1, wherein a plurality of palindromic operation units are provided for each analysis range having different numbers of bases. The palindromic structure detection system for genome sequences according to claim 1 or 2, wherein the analysis range in the genome sequence is sequentially shifted by one base at a time, and palindromic structure detection processing is performed for each shift. The palindromic operation unit includes the first addition unit and the second addition unit that detect a palindrome structure with an even number of non-addition bases sandwiched between n bases from both ends within the analysis range. An even palindrome operation unit,
An odd palindromic operation unit having the first addition unit and the second addition unit for detecting a palindromic structure with an odd number of non-addition bases sandwiched between n bases from both ends within the analysis range; The palindrome structure detection system in the genome sequence according to any one of claims 1 to 3 , wherein The number of non-addition bases sandwiched by n bases from both ends is overlapped with the detection result of the palindrome calculation unit for each analysis range increased in base pair units, and the number of bases forming a pair in the palindrome structure is calculated. The palindrome structure detection system in the genome sequence according to any one of claims 3 to 4, wherein the palindrome structure detection system is obtained. A storage unit for storing detection results obtained by shifting the genome sequence by one base for each palindromic operation unit in the analysis range in which the number of non-addition bases sandwiched between n bases from both ends is increased in units of base pairs Have
At the genomic sequence, is detected palindrome, and center overlay the same of the analysis range, any one of the preceding claims 2, characterized in that the output as detected palindromic The palindromic structure detection system in the genome sequence described in 1. Each of the even palindromic operation unit and the odd palindromic operation unit is composed of n first adders having two inputs, an absolute value unit provided for each adder, and a second adder having n inputs. The palindrome structure detection system in the genome sequence according to claim 4, wherein the palindrome structure is detected. A database in which restriction enzymes are stored corresponding to the base sequences constituting the palindrome structure;
When the palindromic is detected, any one of claim 1, further comprising a retrieval unit for retrieving the restriction enzyme which corresponds to the base sequence of said detected palindrome claim 7 A palindromic structure detection system for genome sequences according to one item .

Images