Methods and systems for genetic analysis

Patent metadata

Field	Value
Publication number	US-11384394-B2
Application number	US-202117548379-A
Country	US
Kind code	B2
Filing date	Dec 10, 2021
Priority date	Jan 17, 2013
Publication date	Jul 12, 2022
Grant date	Jul 12, 2022

Abstract

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.

First claim

What is claimed is:

1. A method for analyzing nucleic acid samples isolated from an individual, comprising:
(a) generating a first subset of nucleic acid molecules from a first nucleic acid sample obtained from said individual;
(b) conducting a first sequencing assay on said first subset of nucleic acid molecules to yield a first result comprising a first nucleic acid sequence wherein said first sequencing assay comprises whole genome sequencing;
(c) generating a second subset of nucleic acid molecules from a second nucleic acid sample of said individual by contacting said second nucleic acid sample with a plurality of capture probes, wherein said plurality of capture probes hybridize to one or more polymorphisms which are based on or extracted from one or more databases of polymorphisms, observed in a population of one or more samples, or a combination thereof, wherein said first sample or said second sample is obtained from said subject at a first time point;
(d) conducting a second sequencing assay on said second subset of nucleic acid molecules to yield a second result comprising a second nucleic acid sequence;
(e) using said plurality of capture probes to generate an additional subset of nucleic acid molecules from an additional nucleic acid sample isolated from an additional sample obtained from said subject at an additional time point different from said first time point;
(f) conducting a third sequencing assay on said additional subset of nucleic acid molecules from said additional nucleic acid sample to yield a third result comprising a third nucleic acid sequence; and
(g) generating a biomedical report that includes biomedical information of said subject, which biomedical information identifies the presence or absence of said one or more polymorphisms identified by said second result or said third result.

2. The method of claim 1 , wherein said biomedical information of said subject 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.

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

4. The method of claim 1 , wherein said one or more polymorphisms are in a set of genes with known biomedically interpretable variants.

5. The method of claim 4 , wherein said set of genes with known biomedically interpretable variants comprise one or more genes or variants associated with cancer.

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

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

8. The method of claim 1 , wherein said additional time point is later than said first time point.

9. The method of claim 1 , further comprising comparing said first result and said second result.

10. The method of claim 1 , further comprising identifying the presence or absence of said one or more polymorphisms in said second nucleic acid sample.

11. The method of claim 10 , wherein said identifying comprises observing an allele frequency of said one or more polymorphisms.

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

13. The method of claim 1 , wherein said plurality of capture probes further comprise barcodes.

14. The method of claim 1 , wherein said samples isolated from said individual are isolated from a body fluid, cell, skin, tissue, organ, or combination thereof.

15. The method of claim 14 , wherein said body fluid sample is a blood plasma sample.

16. The method of claim 14 , wherein said tissue sample is a tissue biopsy sample.

17. The method of claim 1 , wherein said whole genome sequencing produces at least 750,000,000 sequencing reads.

18. The method of claim 1 , wherein said whole genome sequencing produces at least 1,000,000,000 sequencing reads.

19. The method of claim 1 , further comprising:
(i) repeating said third sequencing assay one or more times on one or more subsequent samples to yield an additional result comprising a fourth nucleic acid sequence; and
(ii) generating an additional biomedical report that includes biomedical information of said subject, which biomedical information identifies the presence or absence of said one or more polymorphisms identified by said additional result.

Assignees

• Personalis Inc

Inventors

• Bartha Gabor T
• Chandratillake Gemma
• Chen Richard
• Garcia Sarah
• Lam Hugo Yu Kor
• Luo Shujun
• Pratt Mark R
• West John

Classifications

• C12Q1/6869

  Methods for sequencing · CPC title

• G16B35/00

  ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides · CPC title

• G16B20/20

  Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection · CPC title

• G16B30/00

  ICT specially adapted for sequence analysis involving nucleotides or amino acids · CPC title

• G16C20/60

  In silico combinatorial chemistry · CPC title