Roche Molecular Systems, Inc.

Roche Diagnostics Gmbh

F. Hoffmann-La Roche Ag

Wei-min Liu

Yan Li

Yu Chuan Tai

Rajiv Dua

Lori Steiner

Xiaoju (Max) Ma

Sim-Jasmine Truong

Alison Tsan

Xiaoju Max Ma

Christopher David Santini

Xiaoying Chen

Marcel Fontecha

Chih-Jian Lih

Bryan Hoglund

Janet Jin

Christopher Santini

Provided herein are methods and compositions to classify DLBCL subtypes using quantitative RT-PCR.

Methods and compositions for classifying DLBCL

Accurate variant calling methods for low frequency variants are provided. Sequence reads of targeted ultra-deep sequencing are received and aligned to a reference sequence. Read depths and variant counts for variants of the same class at each location where the reference allele exists on the reference sequence are determined for each sample-amplicon. Based on the read depths and variant counts, a probability value indicating the confidence level that a specific variant at a specific location is a true positive is calculated using methods such as a statistical model based method and a localized method using a reference sample. The probability value is then compared with a threshold level to determine whether the detected variants are true positives.

Rare variant calls in ultra-deep sequencing

Accurate and fast mapping of sequencing reads obtained from a targeted sequencing procedure can be provided. Once a target region is selected, alternate regions of the genome that are sufficiently similar to the target region can be identified. If a sequencing read is more similar to the target region than to an alternate region, then the read can be determined as aligning to the target region. The reads aligning to the target region can then be analyzed to determine whether a mutation exists in the target region. Accordingly, a sequencing read can be compared to the target region and the corresponding alternate regions, and not to the entire genome, thereby providing computational efficiency.

Accurate and fast mapping of reads to genome

A new in-frame deletion was found in exon 19 of the EGFR gene, the exon that is often mutated in tumors. The invention comprises methods of detecting the mutation, methods of prognosis and methods of predicting response to treatment based on the presence of absence of the mutation.

Mutation in the epidermal growth factor receptor kinase domain

Six new mutations were found in exon 19 of the EGFR gene, the exon that is often mutated in tumors. The invention comprises methods of detecting the mutations, methods of prognosis and methods of predicting response to treatment based on the presence of absence of the mutations.

Complex mutations in the epidermal growth factor receptor kinase domain

A method of detecting a target nucleic acid in a test sample utilizes a learning statistical classifier system to build a general linear classifier based on an amplification-dependent parameter for the target and the control nucleic acids, in order to classify the test sample as containing or not containing the target nucleic acid.

Method of detecting nucleic acid targets using a statistical classifier

Methods for generating a normalized expression signal for microarray data based on a theoretical distribution at the unit level to produce a normalized expression signal for the single microarray that is independent of other microarrays. The method typically includes receiving microarray data representing a plurality of probe pairs for a single microarray, determining, for each probe pair, differences between intensities of perfect match (PM) probes and intensities of mismatched (MM) probes, determining a difference signal, D, based on the determined differences, and scaling the difference signal, D, to produce an expression signal, DS. The method also typically includes normalizing the expression signal based on a theoretical distribution at the unit level to produce a normalized expression signal for the single microarray that is independent of other microarrays.

Algorithms for classification of disease subtypes and for prognosis with gene expression profiling

This invention provides methods, compositions, and kits relating to biomarkers whose expression levels are correlated with diffuse large B-cell lymphoma (DLCBL) patients' response to treatment with a CD20 antagonist, such as a CD20 antibody, exemplified by rituximab. The methods, compositions, and kits of the invention can be used to identify DLBCL patients who are likely or not likely, to respond to anti-CD20 treatments.

Growing community of inventors

Dublin, CA, United States of America

Wei-min Liu