Method, apparatus, and electronic device for simulating a target sequence

By iteratively decreasing the comparison parameters of unqualified bases, obtaining target parameters, and simulating parameter fluctuations in targeted capture sequencing data, it solves the problem that existing tools are difficult to simulate sequencing depth fluctuations and base mass distribution, and achieves a more realistic simulation data.

CN110706737BActive Publication Date: 2025-05-30ANNOROAD GENE TECHNOLOGY (BEIJING) CO LTD
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Patent Information

Application Number
CN201910784122.7
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2018-12-29
Filing Date
2019-08-23
Publication Date
2025-05-30
Estimated Expiration
2039-08-23

AI Technical Summary

Technical Problem

Existing gene sequencing data simulation tools are difficult to effectively simulate the fluctuations in sequencing depth and base mass distribution in targeted capture sequencing technology, resulting in a large difference between the simulated data and the real data.

Method used

By obtaining the comparison parameters of the reference sequence and the sequence to be fitted, determine whether the base is qualified, and iteratively subtract the comparison parameters of the unqualified bases to obtain the target parameters used to fit the target sequence, thereby simulating the parameter fluctuations of the real target capture sequencing data.

Benefits of technology

Make the simulated data closer to the real data, accurately simulate the depth fluctuations and base mass distribution of targeted capture sequencing data, and improve the authenticity and reliability of the simulated data.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present application relates to a method, an apparatus, and an electronic device for simulating a target sequence. The method includes: obtaining a reference sequence and a sequence to be fitted; obtaining a comparison parameter of a base based on a reference parameter of the reference sequence corresponding to the base of the target sequence and a reference parameter of the sequence to be fitted, wherein the reference parameter of the sequence to be fitted is obtained based on a plurality of bases; determining whether the base is qualified based on the comparison parameter to obtain qualified bases and unqualified bases; iteratively reducing the comparison parameter of the unqualified bases to obtain a target parameter, the number of iterations of the iterative reduction is based on the comparison parameter, and each iterative reduction is associated with at least one comparison parameter of at least one base; and determining a simulated sequence of the target sequence based on the target parameters of the qualified bases and the unqualified bases. In this way, the parameter fluctuations of real targeted capture sequencing data can be simulated, making the simulated data closer to reality.
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Claims

1. A method for simulating a target sequence, characterized in that, it includes: obtaining a reference sequence and a sequence to be fitted, and the sequence to be fitted contains the target sequence; obtaining a comparison parameter of the base of the target sequence based on the reference parameter of the base of the reference sequence corresponding to the base of the target sequence and the reference parameter of the base of the sequence to be fitted, wherein the reference parameter of the sequence to be fitted is obtained based on the comparison parameter of at least one base of the sequence to be fitted; determining whether the base of the target sequence is qualified based on the comparison parameter of the target sequence to obtain the qualified bases and unqualified bases of the target sequence; iteratively reducing the comparison parameter of the unqualified base to obtain a target parameter, the number of iterations of the iterative reduction is based on the comparison parameter, and each iterative reduction is associated with at least one comparison parameter of at least one base; and determining the simulated sequence of the target sequence based on the target parameter of the qualified base and the unqualified base; the comparison parameter of the base is the difference between the reference parameter of the reference sequence corresponding to the base of the target sequence and the reference parameter of the sequence to be fitted; the reference parameter is the base depth; iteratively reducing the comparison parameter of the unqualified base to obtain a target parameter includes: scoring the bases of the target sequence to obtain base scores; sorting each base in the bases of the target sequence based on the base scores to obtain sorted unqualified bases; and iteratively reducing the comparison parameter of the sorted unqualified bases to obtain a target parameter; iteratively reducing the comparison parameter of the unqualified base of the target sequence to obtain a target parameter includes: after each iterative reduction of the comparison parameter of the sorted unqualified bases, recalculating and sorting the base scores of the unqualified bases based on the reduced comparison parameter, and the recalculated base score is the difference between the base score before calculation and the number of iterations; when the reduced comparison parameter is less than the deviation value for determining whether the base is qualified, the recalculated base score is the difference between the base score before calculation and the product of the number of iterations and the revision coefficient; the revision coefficient is 1 - 10.

2. The method according to claim 1, characterized in that, sorting each base in the unqualified bases of the target sequence based on the base scores to obtain sorted unqualified bases includes: sorting each base in ascending order of the base scores of the target sequence to obtain sorted unqualified bases.

3. The method according to claim 2, characterized in that, iteratively reducing the comparison parameter of the sorted unqualified bases of the target sequence to obtain a target parameter includes: scoring each read segment of the unqualified base to obtain a read segment score; Iteratively delete each read segment of the unqualified bases in descending order of the read segment scores, and the iterative deletion terminates when one of the following conditions is met: The comparison parameter after reduction is less than the parameter threshold; and The number of qualified bases covered by the read segment is greater than the base threshold; Obtain the target parameter by subtracting the number of deleted read segments from the comparison parameter of the unqualified bases.

4. The method according to claim 3, wherein, The base score of the unqualified bases of the target sequence is the sum of one and the quotient of the comparison parameter of the unqualified bases and the reference parameter.

5. The method according to claim 4, wherein, The read segment score is the average of the base scores of all bases covered by the read segment; and Each of the read segments of the unqualified bases is iteratively deleted in descending order of the read segment scores of the read segments.

6. The method according to claim 3, wherein, The base threshold is a natural number greater than or equal to three and less than or equal to five.

7. The method according to claim 1, wherein, The sequence to be fitted is obtained by extending a predetermined unit on at least one side of the target sequence.

8. An apparatus for simulating a target sequence, wherein, comprises: A sequence acquisition unit for acquiring a reference sequence and a sequence to be fitted, and the sequence to be fitted contains the target sequence; A comparison parameter acquisition unit for obtaining a comparison parameter of the bases of the target sequence based on the reference parameter of the bases of the reference sequence corresponding to the bases of the target sequence and the reference parameter of the bases of the sequence to be fitted, wherein the reference parameter of the sequence to be fitted is obtained based on the comparison parameter of at least one base of the sequence to be fitted; A qualified base determination unit for determining whether the bases of the target sequence are qualified based on the comparison parameter of the target sequence to obtain the qualified bases and unqualified bases of the target sequence; An iterative reduction unit for iteratively reducing the comparison parameter of the unqualified bases to obtain a target parameter, the number of iterations of the iterative reduction is based on the comparison parameter, and each iterative reduction is associated with multiple comparison parameters of multiple bases; and A target curve fitting unit for determining the simulated sequence of the target sequence based on the target parameter of the qualified bases and the unqualified bases; The iterative reduction unit includes: A scoring subunit for scoring the unqualified bases of the target sequence to obtain base scores; A sorting subunit for sorting each of the unqualified bases of the target sequence based on the base scores to obtain the sorted unqualified bases; and An iterative subunit for iteratively reducing the comparison parameter of the sorted unqualified bases to obtain a target parameter; Iteratively reducing the comparison parameters of the unqualified bases of the target sequence to obtain target parameters includes: after each iterative reduction of the comparison parameters of the sorted unqualified bases, recalculating and sorting the base scores of the unqualified bases based on the reduced comparison parameters, where the recalculated base score is the difference between the base score before calculation and the number of iterations; when the reduced comparison parameter is less than the deviation value used to determine whether the base is qualified, the recalculated base score is the difference between the base score before calculation and the product of the number of iterations and the revision coefficient; the revision coefficient is 1 - 10.

9. The apparatus according to claim 8, wherein, the iteration subunit is configured to sort each base in ascending order of the base score of the target sequence to obtain sorted unqualified bases.

10. The apparatus according to claim 9, wherein, the iteration subunit is configured to: score each read segment of the unqualified bases of the target sequence to obtain a read segment score; sort in descending order of the read segment scores; iteratively delete the sorted order of the read segments of the unqualified bases, and the iterative deletion terminates when one of the following conditions is met: the reduced comparison parameter is less than the parameter threshold; and the number of qualified bases covered by the read segment is greater than the base threshold; obtain the target parameter based on the comparison parameter of the unqualified bases minus the number of deleted read segments.

11. An electronic device, comprising: a processor; and a memory, in which computer program instructions are stored, and when the computer program instructions are run by the processor, the processor is caused to execute the method for simulating a target sequence according to any one of claims 1 - 7.

Citation Information

Patent Citations

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