Adaptive Biotechnologies Corporation

Fred Hutchinson Cancer Center

Memorial Sloan Kettering Cancer Center

A-Alpha Bio, Inc.

Fred Hutchinson Cancer Research Center

Ryan O Emerson

Harlan Saul Robins

Anna M Sherwood

Christopher Scott Carlson

Mark J Rieder

Robert J Livingston

David Younger

Randolph Lopez

Julie Rubinstein

Jianda Yuan

William S Dewitt, Iii

Arpita Sen

William Sumner DeWitt, Iii

Joe Parsons

William Dewitt Iii

Anna Sherwood

Iii Dewitt William Sumner

Harlan S Robins

Methods are provided for predicting a subject's infection status using high-throughput T cell receptor sequencing to match the subject's TCR repertoire to a known set of disease-associated T cell receptor sequences. The methods of the present invention may be used to predict the status of several infectious agents in a single sample from a subject. Methods are also provided for predicting a subject's HLA status using high-throughput immune receptor sequencing.

Methods for diagnosing infectious disease and determining HLA status using immune repertoire sequencing

The present disclosure provides methods for improving libraries for screening protein-protein interactions (PPI) by excluding amino acid substitutions that are predicted to have a redundant or minimal effect on binding between protein binding partners.

Efficiently characterizing protein-protein interactions

Provided herein are methods for identifying pairs of protein binding partners, mutations of which may inform the discovery of pharmaceutically useful small molecules. The methods disclosed herein may allow for the adaptation of the native protein degradation system to modulate specific disease targets at the protein level, in particular, for targets that have long been considered undruggable.

High-throughput screening methods to identify small molecule targets

Disclosed are methods for determining the immunological status of the adaptive immune system of a subject by identifying and quantifying rearranged DNA (and/or subsequently transcribed RNA) sequences encoding T cell receptor (TCR) and/or immunoglobulin (IG) polypeptides, in a lymphoid DNA-containing sample from the subject. TCR and/or IG sequence diversity and sequence distribution permit immunocompetence and immune repertoire assessment and reflect the degree of T cell or B cell clonality and clonal expansion in the sample. Methods for stratifying patient populations on the basis of immunocompetence including likelihood of responding to immunotherapy are also described.

Immunocompetence assessment by adaptive immune receptor diversity and clonality characterization

Methods and compositions are provided for quantifying the number of biological input molecules of one or more target genes of interest in a PCR. The method comprises steps for amplifying multiple synthetic templates and high throughput sequencing. The method further comprises steps for achieving equal sequencing coverage between targets that do not occur in equal ratios, while mitigating the need for costly deep sequencing methods.

Methods of profiling targeted polynucleotides while mitigating sequencing depth requirements

Methods are provided for correction of amplification bias and quantitation of adaptive immune cells in a sample using synthetic templates that include random oligonucleotide sequences.

Methods using randomer-containing synthetic molecules

Methods of monitoring and measuring dynamic adaptive immune cell responses are provided. High-throughput sequencing of T cell receptor and immunoglobulin loci is used to characterize the breadth of an effector cell response to a stimulus, such as a vaccine or infection. Unique responding effector cell clones and abundance thereof can be determined. Additionally, methods for determining the contribution of responding effector cells to the immunological memory compartment are provided.

Characterization of adaptive immune response to vaccination or infection using immune repertoire sequencing

Compositions and methods are described for standardizing the DNA amplification efficiencies of a highly heterogeneous set of oligonucleotide primers as may typically be used to amplify a heterogeneous set of DNA templates that contains rearranged lymphoid cell DNA encoding T cell receptors (TCR) or immunoglobulins (IG). The presently disclosed embodiments are useful to overcome undesirable bias in the utilization of a subset of amplification primers, which leads to imprecision in multiplexed high throughput sequencing of amplification products to quantify unique TCR or Ig encoding genomes in a sample. Provided is a template composition comprising a diverse plurality of template oligonucleotides in substantially equimolar amounts, for use as a calibration standard for amplification primer sets. Also provided are methods for identifying and correcting biased primer efficiency during amplification.

Compositions and methods for measuring and calibrating amplification bias in multiplexed PCR reactions

The invention is directed to methods for highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune heterodimers from a large number of biological samples containing lymphocytes of interest. Methods of the invention comprise performing a single pairing assay on a pool of source samples to determine nucleic acids encoding paired cognate receptor heterodimer chains in the combined pool. Separately, single-locus, high-throughput sequencing is performed on each individual sample to determine the plurality of sequences encoding one of the two receptor polypeptide chains. Pairs of cognate sequences determined in the pooled sample may then be mapped back to a single source sample by comparing the expression patterns of the single-locus sequences.

Highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune receptor heterodimers from a large number of samples

The invention relates to methods and compositions for estimating the absolute abundance individually for each unique rearranged lymphocyte receptor in a mixed sample.

Multiplexed digital quantitation of rearranged lymphoid receptors in a complex mixture

Disclosed are methods for determining the immunological status of the adaptive immune system of a subject by identifying and quantifying rearranged DNA (and/or subsequently transcribed RNA) sequences encoding T cell receptor (TCR) and/or immunoglobulin (IG) polypeptides, in a lymphoid DNA-containing sample from the subject TCR and/or IG sequence diversity and sequence distribution permit immunocompetence and immune repertoire assessment and reflect the degree of T cell or B cell clonality and clerical expansion in the sample. Methods for stratifying patient populations on the basis of immunocompetence including likelihood of responding to immunotherapy are also described.

Compositions and methods are described for standardizing the DNA amplification efficiencies of a highly heterogeneous set of oligonucleotide primers as may typically be used to amplify a heterogeneous set of DNA templates that contains rearranged lymphoid cell DNA encoding T cell receptors (TCR) or immunoglobulins (IG). The presently disclosed embodiments are useful to overcome undesirable bias in the utilization of a subset of amplification primers, which leads to imprecision in multiplexed high throughput sequencing of amplification products to quantify unique TCR or Ig encoding genomes in a sample. Provided is a composition comprising a diverse plurality of template oligonucleotides in substantially equimolar amounts, for use as a calibration standard for amplification primer sets. Also provided are methods for identifying and correcting biased primer efficiency during amplification.

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Seattle, WA, United States of America

Ryan O Emerson