Methods and systems for genetic analysis

Inventors

West, John • Haudenschild, Christian • Chen, Richard

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

The invention provides personalized genetic testing that performs a first assay on nucleic acid molecules extracted from at least one biological sample from a subject to produce a first set of nucleic acid sequence data. Genetic characteristics are extracted from the first set of nucleic acid sequence data to support obtaining a personalized probe set for the subject. The personalized probe set comprises nucleic acid probe molecules with oligonucleotide-directed genomic content having at least one variable portion and at least one fixed portion.

The variable portion comprises potential neoantigen-causing variants of the subject, identified by alignment of the first set of nucleic acid sequence data to a reference genome from the subject. The fixed portion is selected from cancer driver genes, genes involved in the pharmacogenomics of cancer drugs, genes involved in Mendelian immunological diseases, genes related to inherited forms of cancer, genes associated with tumor escape from targeted or immune cancer therapy, HLA typing, and variants common in the population used by B-allele methods to detect structural variation.

The probe set is then used to perform a second assay on nucleic acid molecules extracted from one or more additional biological samples. Biomedical information of the subject is output based on an analysis comparing results from the first assay with results from the second assay, and the biomedical information comprises one or more biomedical outputs that suggest, select, designate, recommend, or otherwise determine a course of treatment and/or prevention of a disease or condition, where the course of treatment comprises an anti-cancer therapy.

Claims Coverage

Two independent claims define the scope of the personalized genetic testing workflow. Both claims share a subject-specific personalized probe set with variable neoantigen-causing content and specified fixed genomic content, together with a first-assay to second-assay comparison workflow; one claim further requires treatment and/or prevention outputs including anti-cancer therapy.

The claims center on constructing an individualized probe set that targets potential neoantigen-causing variants via alignment to a reference genome while also including specified fixed genomic content categories, then using that probe set in a second assay and outputting biomedical information based on comparison of the first and second assay results. One independent claim further requires biomedical outputs that determine a course of treatment and/or prevention including anti-cancer therapy.

Stated Advantages

Documented Applications