Methods and systems for genetic analysis

11408,033

17/078857

October 23, 2020

This disclosure provides systems and methods for sample processing and data analysis. Sample processing may include nucleic acid sample processing and subsequent sequencing. Some or all of a nucleic acid sample may be sequenced to provide sequence information, which may be stored or otherwise maintained in an electronic storage location. The sequence information may be analyzed with the aid of a computer processor, and the analyzed sequence information may be stored in an electronic storage location that may include a pool or collection of sequence information and analyzed sequence information generated from the nucleic acid sample. Methods and systems of the present disclosure can be used, for example, for the analysis of a nucleic acid sample, for producing one or more libraries, and for producing biomedical reports. Methods and systems of the disclosure can aid in the diagnosis, monitoring, treatment, and prevention of one or more diseases and conditions.

Personalis, Inc. (Menlo Park, CA, US)

Personalis, Inc. (Menlo Park, CA, US)

1. A method for analyzing a nucleic acid sample obtained from an individual, comprising: (a) producing, with the aid of a computer processor, a plurality of capture probes, wherein said plurality of capture probes hybridize to a plurality of polymorphisms, wherein said plurality of polymorphisms are in sequences encoding genes with known biomedically interpretable variants, and wherein said plurality of polymorphisms are based on or extracted from one or more databases of polymorphisms and are observed in a population of one or more samples; (b) contacting said nucleic acid sample with said plurality of capture probes produced in (a); (c) conducting a sequencing assay on a subset of nucleic acid molecules generated from said nucleic acid sample in step (b) to yield a result comprising a nucleic acid sequence, thereby analyzing said nucleic acid sample; and (d) repeating steps (b)-(c) on a subsequently obtained biological sample from said individual.

2. The method of claim 1 , further comprising, subsequent to (c), generating a biomedical report that includes biomedical information of said individual, which biomedical information is indicative of said result.

3. The method of claim 2 , wherein said biomedical information of said individual is predictive, prognostic, or diagnostic of one or more biomedical features selected from the group consisting of disease state, efficacy of a drug therapy, prediction of optimal drug dosage, recommendation of one or more therapies, and recommendation of a course of treatment of a disease.

4. The method of claim 1 , wherein said plurality of polymorphisms comprise one or more insertions, deletions, structural variant junctions, variable length tandem repeats, single nucleotide mutations, or a combination thereof.

5. The method of claim 1 , wherein said sequences encoding genes with known biomedically interpretable variants comprise a plurality of sequences encoding genes associated with cancer.

6. The method of claim 1 , further comprising identifying the presence or absence of said plurality of polymorphisms in said nucleic acid sample.

7. The method of claim 2 , wherein said identifying comprises observing an allele frequency of said plurality of polymorphisms.

8. The method of claim 1 , wherein said plurality of capture probes are in a hybridization array.

9. The method of claim 1 , wherein said plurality of capture probes are conjugated to beads.

10. The method of claim 1 , wherein said plurality of capture probes further comprises barcodes.

11. The method of claim 1 , wherein said nucleic acid sample obtained from said individual is from a body fluid, cell, skin, tissue, organ, or combination thereof.

12. The method of claim 11 , wherein said body fluid is blood plasma.

13. The method of claim 12 , wherein said plasma sample is obtained from said individual at a first time point, and further comprising, subsequent to (c), using said capture probes to generate an additional subset of nucleic acid molecules from an additional nucleic acid sample isolated from an additional plasma sample obtained from said individual at an additional time point different from said first time point.

14. The method of claim 13 , wherein said first time point and said additional time point are at least 1 week apart, or more.

15. The method of claim 13 , wherein said first time point and said additional time point are at least 1 month apart, or more.

16. The method of claim 13 , wherein said additional time point is later than said first time point.

17. The method of claim 13 , wherein said additional time point is earlier than said first time point.

18. The method of claim 11 , wherein said tissue is a tissue biopsy.

19. The method of claim 1 , wherein said subsequently obtained biological sample is a plasma sample.

20. The method of claim 1 , wherein said subsequently obtained biological sample is a tissue biopsy sample.

21. The method of claim 1 , wherein said one or more databases of polymorphisms comprises a biomedical database.

22. The method of claim 1 , wherein said one or more polymorphisms are observed in a population of a single sample.

23. The method of claim 1 , wherein said plurality of polymorphisms are based on or extracted from said one or more databases of polymorphisms and observed in said population, wherein said population comprises a plurality of samples.

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