Methods and systems for genetic analysis
Inventors
Bartha, Gabor T. • Chandratillake, Gemma • Chen, Richard • Garcia, Sarah • Lam, Hugo Yu Kor • Luo, Shujun • Pratt, Mark R. • West, John
Assignees
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Publication Number
US-12084717-B2
Publication Date
2024-09-10
Expiration Date
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.
Core Innovation
The invention analyzes nucleic acid samples obtained from a subject by generating a first subset from a tumor sample and performing a first sequencing assay comprising whole genome sequencing to yield a first result comprising a first nucleic acid sequence. In parallel, the invention generates a second subset from a second nucleic acid sample obtained at a second time point by contacting the sample with a plurality of pulldown probes.
The plurality of pulldown probes comprises 10 or more pulldown probes with different sequences, and hybridizes to a genomic region feature comprising a plurality of polymorphisms based on or extracted from one or more databases of polymorphisms observed in a population. The second sequencing assay comprises sequencing by synthesis and yields a second result comprising a second nucleic acid sequence.
A computer processor combines the first result and the second result to analyze the nucleic acid samples. The method generates a biomedical report that includes biomedical information of the subject, where the biomedical information identifies the presence or absence of the plurality of polymorphisms identified by the second result.
Claims Coverage
The independent claim covers a combined sequencing analysis workflow with six inventive features centered on paired sampling, probe-based polymorphism targeting, distinct sequencing assay types, computer-processor combination of results, and biomedical report generation.
Paired subset generation from tumor and time-point samples
Generating a first subset of nucleic acid molecules from a first nucleic acid sample obtained from a tumor sample of the subject, and generating a second subset of nucleic acid molecules from a second nucleic acid sample of the subject at a second time point.
Whole genome sequencing of the first subset
Conducting a first sequencing assay on the first subset, wherein the first sequencing assay comprises whole genome sequencing and yields a first result comprising a first nucleic acid sequence.
Database-driven polymorphism-targeted pulldown probe set
Contacting the second nucleic acid sample with a plurality of pulldown probes comprising 10 or more pulldown probes with different sequences, where the plurality hybridizes to a genomic region feature comprising a plurality of polymorphisms based on or extracted from one or more databases of polymorphisms observed in a population.
Sequencing by synthesis of the probe-enriched subset
Conducting a second sequencing assay on the second subset, wherein the second sequencing assay comprises sequencing by synthesis and yields a second result comprising a second nucleic acid sequence.
Computer-processor combination of sequencing results
Combining, with the aid of a computer processor, the first result and the second result to analyze the nucleic acid samples.
Biomedical report identifying polymorphism presence or absence
Generating a biomedical report that includes biomedical information of the subject, wherein the biomedical information identifies the presence or absence of the plurality of polymorphisms identified by the second result.
The claim coverage centers on a workflow that pairs whole genome sequencing from a tumor-derived subset with a probe-enriched subset generated using database-driven polymorphism-targeted pulldown probes, sequences the probe-enriched subset by sequencing by synthesis, combines both results with a computer processor, and produces a biomedical report that identifies presence or absence of polymorphisms from the second result.
Stated Advantages
Improved capture-probe-based sequencing performance/sensitivity.
Biomedical reports identify presence or absence of polymorphisms identified by the second result.
Documented Applications
Disease diagnosis.
Disease monitoring.
Treatment/prevention guidance.
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