公开(公告)号：US20240420799A1

公开(公告)日：2024-12-19

申请号：US18718989

申请日：2022-12-06

Applicant: Foundation Medicine, Inc.

Inventor： Yanmei HUANG ,  Jason D. HUGHES

IPC: G16B20/20 ,  C12Q1/6806 ,  C12Q1/6855 ,  C12Q1/6874 ,  C12Q1/6886 ,  G16B20/10 ,  G16H20/10 ,  G16H50/20

Abstract: Methods for determining the reliability of a prediction of somatic or germline origin for a variant sequence in a sample from a subject are described. The methods comprise determining a tumor fraction metric that characterizes a tumor fraction of the sample based on the sequence read data; determining a copy number metric for a variant sequence present in the sample based on the sequence read data; generating a reliability parameter for predicting somatic or germline origin for the variant sequence based on the tumor fraction metric and the copy number metric; and comparing the reliability parameter to a predetermined threshold to determine if the prediction of somatic or germline origin for the variant sequence is reliable.

公开(公告)号：US20240420797A1

公开(公告)日：2024-12-19

申请号：US18697958

申请日：2022-10-07

Applicant: Foundation Medicine, Inc.

Inventor： Jason D. HUGHES ,  Bernard FENDLER ,  Justin NEWBERG

IPC: G16B20/10 ,  C12Q1/6806 ,  C12Q1/6855 ,  C12Q1/6874 ,  G16B45/00 ,  G16H20/10 ,  G16H50/20 ,  G16H50/30

Abstract: Methods and systems for calling copy number alterations (CNAs), including methods and systems for fitting a grid-based copy number model to sequence read data are described herein. The method can include generating a minor allele coverage ratio and a major allele coverage ratio for a plurality of genetic loci, transforming the allele coverage data, and fitting a copy number grid model to the data. The fit copy number grid model may then be used to assign a copy number state or call a copy number alteration. The copy number grid model and the transformed allele coverage ratio data may be displayed for consideration of the presented model, which allows for more efficient data interpretation and calling of a copy number state or copy number alteration.

公开(公告)号：US20250154604A1

公开(公告)日：2025-05-15

申请号：US19020349

申请日：2025-01-14

Applicant: Foundation Medicine, Inc.

Inventor： Yanmei HUANG ,  Jason D. HUGHES

IPC: C12Q1/6886 ,  G16B20/10 ,  G16B20/20

Abstract: Methods and systems for determining a tumor DNA fraction for a sample from a subject are described. In some instances, the methods comprise receiving sequence read data for a plurality of sequence reads derived from the sample from the subject; determining a variant allele frequency (VAF) for one or more variants detected in the sample based on the sequence read data; generating an empirical distribution of tumor DNA fraction values as a function of the determined VAF for the one or more variants; fitting a model to the empirical distribution of tumor DNA fraction values; and determining a tumor DNA fraction for the sample based on the model.

公开(公告)号：US20220243279A1

公开(公告)日：2022-08-04

申请号：US17612966

申请日：2020-05-20

Applicant: Foundation Medicine, Inc.

Inventor： Bernard FENDLER ,  Jason D. HUGHES ,  Steven ROELS

IPC: C12Q1/6886 ,  G16B40/20 ,  G16B20/20

Abstract: Disclosed herein are, at least in part, methods of determining a tumor fraction of a sample from a subject. The methods can include, for example, acquiring a value for a target variable associated with a subgenomic interval in the sample; determining, from the target variable, a certainty metric; accessing a determined relationship between a stored certainty metric and a stored tumor fraction; and determining, with reference to the certainty metric and the determined relationship, the tumor fraction of the sample.

公开(公告)号：US20250101537A1

公开(公告)日：2025-03-27

申请号：US18892130

申请日：2024-09-20

Applicant: Foundation Medicine, Inc.

Inventor： Brennan DECKER ,  Alexander FINE ,  Zheng KUANG ,  Douglas A. MATA ,  Jason D. HUGHES ,  Meagan Kathleen MONTESION ,  Radwa SHARAF

IPC: C12Q1/70 ,  C12Q1/6886 ,  G16B30/00 ,  G16B40/20

Abstract: Disclosed herein are methods and systems for determining an origin of viral sequence reads detected in a sample (e.g., a liquid biopsy sample) from an individual. The sample may contain cfDNA fragments of varying fragment lengths. Embodiments of the present disclosure can receive sequence read data associated with the sample, which may be a liquid biopsy sample. The sequence read data can be used to determine if one or more viral sequence reads are detected in the sample. If the viral sequence reads are detected, the system can determine one or more fragmentomic features based on the sequence read data. The system can then generate an output indicative of the origin of the viral sequence reads by inputting the fragmentomic features into a statistical model including, for example, a trained machine-learning model. Based on the output, the system can then determine whether the viral sequence reads originate from a tumor.

公开(公告)号：US20240412812A1

公开(公告)日：2024-12-12

申请号：US18698747

申请日：2022-10-07

Applicant: Foundation Medicine, Inc.

Inventor： Jason D. HUGHES ,  Justin NEWBERG

IPC: G16B20/10 ,  G16B20/20

Abstract: Methods and systems for performing iterative contamination detection and segmentation of sequence read data are described. The methods are based on comparing a distribution of minor allele frequencies (MAPs) for a plurality of single nucleotide polymorphisms (SNPs) detected in the sample to an expected distribution of minor allele frequencies for a plurality of selected SNP loci, and adjusting a MAP threshold used to discriminate between aberrant SNPs (SNPs exhibiting a different distribution of MAP values than that expected for the plurality of selected SNPs) and those conforming to the expected distribution of minor allele frequencies for the plurality of selected SNP loci. The methods may be used to estimate the degree of contamination in a sample and to provide segmentation of sequence read data for the sample, and may further comprise building a copy number model that predicts a copy number for one or more gene loci.

公开(公告)号：US20240404626A1

公开(公告)日：2024-12-05

申请号：US18698746

申请日：2022-10-07

Applicant: Foundation Medicine, Inc.

Inventor： Bernard FENDLER ,  Jason D. HUGHES

IPC: G16B20/10 ,  G16B20/20 ,  G16B30/10

Abstract: Methods and systems for automated calling of copy number alterations (CNAs) are described. The methods and systems utilize sequencing-based coverage ratio data, allele fraction data, segmentation data, and copy number model data for one or more gene loci within one or more subgenomic intervals in a sample from a subject to detect amplifications and deletions of gene loci, and apply a number of thresholds and filters to provide automated calling of CNAs with improved reliability while eliminating the need for process-matched controls and manual curation of the sequencing data.

公开(公告)号：US20230242975A1

公开(公告)日：2023-08-03

申请号：US18008410

申请日：2021-06-03

Applicant: Foundation Medicine, Inc.

Inventor： Yanmei HUANG ,  Jason D. HUGHES ,  Kyle GOWEN

IPC: C12Q1/6844 ,  C12Q1/6886 ,  G16B20/20 ,  C12Q1/6869 ,  G16B30/10

CPC classification number: C12Q1/6844 ,  C12Q1/6886 ,  G16B20/20 ,  C12Q1/6869 ,  G16B30/10 ,  C12Q2600/16

Abstract: Described herein are methods for distinguishing between somatic and germline variants, and devices for implementing such methods. In certain implementation of the methods, the method can include identifying a genomic sequence of interest in a patient sample at a genomic locus; identifying one or more proxy genomic sequences for the sequence of interest; comparing an observed frequency of the sequence of interest to a centrality measure of observed frequencies of the one or more proxy genomic sequences; and based on the comparison, characterizing the genomic sequence of interest as either germline or somatic.