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

Personalis Inc

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

A method is provided for processing nucleic acid sample(s) of a subject by generating at least a first subset of nucleic acid molecules and a second subset of nucleic acid molecules from one or more nucleic acid samples. The first subset is selectively enriched with probes that selectively enrich for the genomic feature consisting of methylation state, while the second subset is selectively enriched with probes that selectively enrich for the genomic feature consisting of single nucleotide polymorphisms (SNPs). The genomic features for each subset are selectively enriched relative to other probes that do not selectively enrich for the genomic features.

The method subjects the first subset to a first assay to yield a first result comprising a first nucleic acid sequence and subjects the second subset to a second assay to yield a second result comprising a second nucleic acid sequence. The processed outputs from the two assays are then combined with the aid of a computer processor. The computer-processor-combined output generates an output comprising a consensus sequence from the first nucleic acid sequence and the second nucleic acid sequence.

Claims Coverage

The independent claim covers a nucleic-acid sample processing workflow that generates two probe-enriched subsets for distinct genomic features, performs distinct assays to obtain nucleic-acid sequences, and uses a computer processor to combine results into a consensus sequence. The independent claim includes three main inventive blocks.

The core coverage lies in probe-selective enrichment for methylation state versus SNPs, assay-based generation of sequence results for each enriched subset, and computer-processor combination of the resulting sequences into a consensus sequence.

Stated Advantages

Documented Applications