The Translational Genomics Research Institute

The Ohio State University

Cancer Research Technology Limited

Muhammed Murtaza

Tania Contente-Cuomo

Timothy K McDaniel

Nitzan Rosenfeld

Francesco Marass

William Hendricks

Maria De Las Nieves Perdigones Borderias

Gwendolen Lorch

Tim Forshew

The invention provides a method for validating patient-specific oligos using spike-in sequences.

Method for validating assays of biological samples

Methods are provided for treating lung cancer, and more particularly for treating pulmonary adenocarcinoma in a canine subject. The method may comprise assaying a biological sample from the canine subject, such as a tumor sample or a plasma sample, for a mutation in the HER2 gene. The mutation may include HER2 V659E, HER2 A664T, or HER2 K676E. If one or more of the mutations is present in the biological sample, the methods further include treating the canine subject by administering a therapeutically effective amount of an inhibitor of HER2. For example, a HER2 V659E may indicate increase sensitivity to a HER2 inhibitor. The HER2 inhibitor may include a small molecule HER2 inhibitor, such as trastuzumab, neratinib, lapatinib, erlotinib, and pertuzumab.

Identification of HER2 mutations in lung cancer and methods of treatment

The invention provides a tagged sequencing library and methods for tagging low abundance target sequences and generating a sequencing library for detecting low abundance target sequences.

Molecular tagging methods and sequencing libraries

The present invention provides a method of determining integrity and/or quantity of cell free DNA (cfDNA) in a biological sample comprising amplifying target sequences with at least a first primer/probe set and at least a second primer probe/set, amplifying the target sequences of differing lengths, and monitoring for detection of the labels of the oligonucleotide probes, and determining the integrity and/or quantity of the cfDNA based on the level of detection of the label of the oligonucleotide probe from the first primer/probe set compared to the level detection of the label of the oligonucleotide probe from the second primer/probe set. The present invention also provides methods for generating a library with the cfDNA for sequencing and analysis.

Quality assessment of circulating cell-free DNA using multiplexed droplet digital PCR

The present invention provides a method of determining integrity and/or quantity of cell free DNA (cfDNA) in a bio logical sample comprising amplifying target sequences with at least a first primer/probe set and at least a second primer probe/set, amplifying the target sequences of differing lengths, and monitoring for detection of the labels of the oligonucleotide probes, and determining the integrity and/or quantity of the cfDNA based on the level of detection of the label of the oligonucleotide probe from the first primer/probe set compared to the level detection of the label of the oligonucleotide probe from the second primer/probe set. The present invention also provides methods for generating a library with the cfDNA for sequencing and analysis.

The present invention provides a method for detecting a genetic variant in a region of interest in a DNA sample comprising (i) determining, for a given sequencing platform, sequencing process and sequencing depth, the distribution of the number of reads supporting a genetic variant or plurality of genetic variants expected to be observed in the sequencing results of amplification reactions due to amplification and sequencing error (read count distribution); (ii) based on the read count distribution determined in step (i), establishing a threshold frequency at or above which the genetic variant must be observed in sequencing results of amplification reactions to assign a positive determination for the presence of the genetic variant in a given amplification reaction; (iii) partitioning the DNA sample into a plurality of replicate amplification reactions, so that the mean number of amplifiable template molecules of the region of interest in a replicate amplification reaction is fewer than the reciprocal of the threshold frequency determined in step (ii); (iv) performing the amplification reactions of step (iii) and sequencing the products of amplification reactions, (v) based on step (ii) and the results of step (iv), determining the presence/absence of the genetic variant in each replicate amplification reaction; and (vi) integrating the results of (v) to determine the presence/absence of the genetic variant in the region of interest in the DNA sample.

Growing community of inventors

Phoenix, AZ, United States of America

Muhammed Murtaza