Customized assays for personalized cancer monitoring

Inventors

West, John • GOODMAN, LAURIE • Chen, Richard

Assignees

Personalis Inc

Abstract

The present disclosure provides methods and systems for personalized genetic testing of disease in a subject, in particular for identifying and tracking genetic mutations identified in an individual subject to monitor for cancer or for the spread or recurrence of the disease. In some embodiments, custom assays, including custom panels designed to target sequence data corresponding to both subject-specific loci and other loci known for cancer-causing or therapy resistance mutations, are designed based upon the sequencing of a screening biopsy sample. Such custom assays are then run on subsequently obtained tissue samples, such as tissue obtained from a surgical resection of a primary or metastatic tumor or from a lymph node biopsy. The subsequently obtained tissue samples can be taken from the subject at various time points after an initial screening biopsy to further allow for extended monitoring of the subject for spread or recurrence of the disease.

Core Innovation

The invention informs therapy decisions in a subject by generating nucleic acid sequencing data from nucleic acid molecules derived from a first biological sample. The first sequencing assay comprises whole genome sequencing or whole exome sequencing, and the sequencing depth is about 10.0× or higher.

The nucleic acid sequencing data are processed to identify a plurality of nucleic acid sequences having genetic characteristics. The genetic characteristics include a set of genetic variants identified with respect to a reference, where the set comprises one or more multiple nucleotide polymorphisms, and at least a subset of individual polymorphisms comprising the one or more multiple nucleotide polymorphisms are not in phase.

The set of genetic variants is combined to generate a signature of the subject. A probe set comprising a plurality of nucleic acid probe molecules is then used to selectively enrich or amplify the set of genetic variants comprising the subject signature from nucleic acid molecules derived from a second biological sample, and a personalized sequencing assay identifies at least a subset of the genetic variants in the second biological sample, where the presence of the subset informs therapy decisions.

Claims Coverage

One independent claim is provided. It requires five major inventive features: initial whole genome or whole exome sequencing from a first sample, generation of a subject genetic variant signature with at least some out-of-phase multiple nucleotide polymorphisms, targeted enrichment or amplification from a second sample using a probe set configured to capture that signature, a personalized sequencing assay on the enriched library, and use of the detected variants to inform therapy decisions.

The independent claim centers on using whole genome or whole exome sequencing to generate a subject genetic signature that explicitly includes out-of-phase multiple nucleotide polymorphisms, then using a probe set to enrich or amplify that signature from a second biological sample for a personalized sequencing assay, where the detected variant presence informs therapy decisions.

Stated Advantages

Documented Applications