Adaptive Biotechnologies Corporation

Fred Hutchinson Cancer Center

Memorial Sloan Kettering Cancer Center

Institute of Advanced Study

Institute for Advanced Study

Digital Biotechnologies, Inc.

Fred Hutchinson Cancer Research Center

Harlan Saul Robins

Ryan O Emerson

Anna M Sherwood

Christopher Scott Carlson

Robert J Livingston

Mark J Rieder

Julie Rubinstein

Edus H Warren, Iii

Jianda Yuan

William S Dewitt, Iii

Philip D Greenberg

Thomas M Schmitt

Mark Klinger

Raul Rabadan

Aude Georgiana Chapuis

Jason H Bielas

Arnold Levine

Thomas M Snyder

Daniela Witten

Michael Krasnitz

Julia Greissl

Jonathan M Carlson

William Sumner DeWitt, Iii

Joe Parsons

Anna Sherwood

Edus H Warren

William Dewitt Iii

Daniella Witten

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

Provided are synthetic strands for nucleic acid sequencing. In some embodiments, the strands include a plurality of rotatable molecular disks. The plurality of rotatable molecular disks comprises molecular disks each comprising a first moiety that binds to adenine (A), a second moiety that binds to cytosine (C), a third moiety that binds to guanine (G), and a fourth moiety that binds to thymine (T), uracil (U), or both (T/U). The first, second, third, and fourth moieties are spaced about the perimeter of the molecular disk. The molecular disks enable hybridization of the synthetic strand to a nucleic acid, where the rotational positions of the molecular disks indicate the sequence of the nucleic acid. Also provided are methods of using the synthetic strands, as well as related compositions, kits, and nucleic acid sequencing systems. Stem-loop structure-based sequencing methods and related compositions, kits, and nucleic acid sequencing systems are also provided.

Nucleic acid sequencing compositions and methods

Provided are methods for assessing T cell receptor β chain complementary determining region 3 (TCRβ CDR3) sequences. In certain embodiments, the methods comprise assessing TCRβ CDR3 sequences determined from a sample obtained from a subject having or suspected of having a tick bite for the presence or absence of one or more TCRβ CDR3 sequences set forth in the present disclosure. According to some embodiments, at the time of the assessing, the subject is seronegative for Lyme disease and/or has one or more non-specific symptoms consistent with Lyme disease. Also provided are methods comprising administering a Lyme disease therapy to a subject identified as comprising T cells that express a T cell receptor β chain (TCRβ) comprising a TCRβ CDR3 sequence set forth in the present disclosure.

Lyme disease-associated T cell receptor-related methods

Provided are methods of assessing a biological sample obtained from an individual for the presence of a T cell that expresses a T cell receptor (TCR) comprising a TCRβ CDR3 sequence set forth in Table 1. Such methods further comprise identifying the individual as having COVID-19 when the presence of the TCR is detected. The presence of one or more of these TCRs may be of use in prognosticating severity of COVID-19 in the individual and the individual may be treated based on the expected severity of COVID-19. Treatment methods may include administering to the individual a T cell engineered to express the TCR. Such engineered T cells are also disclosed. Also provided are compositions and multimers that find use, e.g., in practicing the methods of the present disclosure.

T cell receptor sequences diagnostic for COVID-19 and related compositions

Provided are synthetic strands for nucleic acid sequencing. In some embodiments, the strands include a plurality of rotatable solid supports. The plurality of rotatable solid supports comprises solid supports each comprising on its surface a first moiety that binds to adenine (A), a second moiety that binds to cytosine (C), a third moiety that binds to guanine (G), a fourth moiety that binds to thymine (T), uracil (U), or both (T/U). Each of such solid supports further comprises on its surface a position marker that indicates the rotational position of the solid support, where the first, second, third, and fourth moieties are spaced about the circumference of the solid support. The solid supports enable hybridization of the synthetic strand to a nucleic acid. Also provided are methods of using the synthetic strands, as well as related compositions, kits, and nucleic acid sequencing systems.

Synthetic strands for nucleic acid sequencing and related methods and systems

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

A method of measuring immunocompetence is described. This method provides a means for assessing the effects of diseases or conditions that compromise the immune system and of therapies aimed to reconstitute it. This method is based on quantifying T-cell diversity by calculating the number of diverse T-cell receptor (TCR) beta chain variable regions from blood cells.

Method of measuring adaptive immunity

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

Methods are provided for identifying T cell receptors that specifically bind a particular antigenic target and can be used as therapeutics against disease.

Method of identifying human compatible T cell receptors specific for an antigenic target

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Seattle, WA, United States of America

Harlan Saul Robins