Abstract: Provided are methods for assessing T cell receptor ? chain complementary determining region 3 (TCR? CDR3) sequences. In certain embodiments, prior to the assessing, the subject has been identified as having, or is suspected of having, inflammatory bowel disease (IBD). According to some embodiments, at the time of the assessing, the subject has one or more non-specific symptoms consistent with Crohn's disease. Also provided are methods comprising administering a Crohn's disease therapy to a subject identified as comprising T cells that express a T cell receptor ? chain (TCR?) comprising a TCR? CDR3 sequence set forth in the present disclosure. Computer readable media and systems for assessing TCR? CDR3 sequences are also provided.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

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

Abstract: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human Wilms tumor protein 1 (WT 1) epitopes and mesothelin epitopes), T cells expressing such high affinity antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

Abstract: 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.

Abstract: 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.

Abstract: 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.

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

Abstract: 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.

Abstract: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human Wilms tumor protein 1 (WT 1) epitopes and mesothelin epitopes), T cells expressing such high affinity antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.