Guardant Health, Inc.

Veracyte, Inc.

Verinata Health, Inc.

Illumina Corporation

Darya Chudova

Helmy A Eltoukhy

Stefanie Ann Ward Mortimer

Giulia C Kennedy

Jonathan I Wilde

Eric T Wang

Diana Abdueva

Amirali Talasaz

Hui Wang

Nusrat Rabbee

Richard P Rava

Sven Duenwald

Keith W Jones

AmirAli Talasaz

Moraima Pagan

Bonnie H Anderson

Catalin Barbacioru

Marcin Sikora

David A Comstock

Anupama Srinivasan

Andrew Kennedy

Ariel Jaimovich

Elena Helman

Gengxin Chen

Dimitri Skvortsov

Martina I Lefterova

Katie Julia Quinn

Aliaksandr Artsiomenka

Stephen Fairclough

P Sean Walsh

Daniel Pankratz

Rebecca Nagy

Kimberley Banks

Helmy Eltoukhy

Richard Lanman

Christine Lee

Values for tumor mutation burden from different samples can be made more comparable to each other or control standards by a normalization regime that takes into account the minor allele fraction of highly rated mutations in a sample. Such analysis can provide an indication where the tumor mutation burden of a test sample lies on a distribution of tumor mutation burdens in a control population, and thus, whether the individual providing the test sample is likely to be amenable to immunotherapy to treat cancer.

Normalizing tumor mutation burden

Provided herein are methods for determining the microsatellite instability status of samples. In one aspect, the methods include quantifying a number of different repeat lengths present at each of a plurality of microsatellite loci from sequence information to generate a site score for each of the plurality of the microsatellite loci. The methods also include comparing the site score of a given microsatellite locus to a site specific trained threshold for the given microsatellite locus for each of the plurality of the microsatellite loci and calling the given microsatellite locus as being unstable when the site score of the given microsatellite locus exceeds the site specific trained threshold for the given microsatellite locus to generate a microsatellite instability score, which includes a number of unstable microsatellite loci from the plurality of the microsatellite loci.

Microsatellite instability detection in cell-free DNA

The present disclosure provides a method for enriching for multiple genomic regions using a first bait set that selectively hybridizes to a first set of genomic regions of a nucleic acid sample and a second bait set that selectively hybridizes to a second set of genomic regions of the nucleic acid sample. These bait set panels can selectively enrich for one or more nucleosome-associated regions of a genome, said nucleosome-associated regions comprising genomic regions having one or more genomic base positions with differential nucleosomal occupancy, wherein the differential nucleosomal occupancy is characteristic of a cell or tissue type of origin or disease state.

Methods for multi-resolution analysis of cell-free nucleic acids

The present invention relates to compositions and methods for molecular profiling and diagnostics for genetic disorders and cancer, including but not limited to gene expression product markers associated with cancer or genetic disorders. In particular, the present invention provides algorithms and methods of classifying cancer, for example, thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.

Methods for treatment of thyroid cancer

The present invention relates to compositions, kits, and methods for molecular profiling and cancer diagnostics, including but not limited to genomic DNA markers associated with cancer. In particular, the present invention provides molecular profiles associated with thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.

Methods for classification of tissue samples as positive or negative for cancer

Provided herein are methods for detecting tumor mutational burden (TMB) in subjects. In one aspect, the methods include determining observed mutational counts from sequence information obtained from nucleic acids in samples from the subjects and determining a tumor fraction and/or a coverage of the nucleic acids to generate sequencing parameters. The methods also include determining an expected mutational fraction and/or an expected distribution of the expected mutational fraction given the sequencing parameters to generate an expected result, and adjusting the observed mutational count given the expected result to generate an adjusted result, thereby detecting the TMB in the subject. Other aspects are directed to methods of selecting customized therapies for treating cancer in subjects, and methods of treating cancer in subjects. Yet other aspects include related systems and computer readable media used to detect TMB in subjects.

Methods and systems for adjusting tumor mutational burden by tumor fraction and coverage

The disclosure relates to computer technology for precision diagnosis of various states of genetic material such as a gene sequenced from cell-free DNA in a sample. The state may include a somatic homozygous deletion, a somatic heterozygous deletion, a copy number variation, or other states. A computer system may generate competing probabilistic models that each output a probability that the genetic material is in a certain state. Each model may be trained on a training sample set to output a probability that the genetic material is in a respective state. In some embodiments, the computer system may use various probabilistic distributions to generate the models. For example, the computer system may use a beta-binomial distribution, a binomial distribution, a normal (also referred to as 'Gaussian') distribution, or other type of probabilistic modeling techniques.

Computational modeling of loss of function based on allelic frequency

Disclosed herein are methods, compositions, and devices for use in the early detection of cancer. The methods include preparing cell-free nucleic acid molecules from a subject for sequencing, sequencing a panel of regions in the cell-free nucleic acid molecules, and detecting one or more markers that are indicative of a cancer.

Methods for early detection of cancer

Disclosed are methods for determining copy number variation (CNV) known or suspected to be associated with a variety of medical conditions, including syndromes related to CNV of subchromosomal regions. In some embodiments, methods are provided for determining CNV of fetuses using maternal samples comprising maternal and fetal cell free DNA. Some embodiments disclosed herein provide methods to improve the sensitivity and/or specificity of sequence data analysis by removing within-sample GC-content bias. In some embodiments, removal of within-sample GC-content bias is based on sequence data corrected for systematic variation common across unaffected training samples. In some embodiments, syndrome related biases in sample data are also removed to increase signal to noise ratio. Also disclosed are systems for evaluation of CNV of sequences of interest.

Detecting fetal sub-chromosomal aneuploidies

Growing community of inventors

San Jose, CA, United States of America

Darya Chudova