Dataset Information

How repertoire data are changing antibody science.

ABSTRACT: Antibodies are vital proteins of the immune system that recognize potentially harmful molecules and initiate their removal. Mammals can efficiently create vast numbers of antibodies with different sequences capable of binding to any antigen with high affinity and specificity. Because they can be developed to bind to many disease agents, antibodies can be used as therapeutics. In an organism, after antigen exposure, antibodies specific to that antigen are enriched through clonal selection, expansion, and somatic hypermutation. The antibodies present in an organism therefore report on its immune status, describe its innate ability to deal with harmful substances, and reveal how it has previously responded. Next-generation sequencing technologies are being increasingly used to query the antibody, or B-cell receptor (BCR), sequence repertoire, and the amount of BCR data in public repositories is growing. The Observed Antibody Space database, for example, currently contains over a billion sequences from 68 different studies. Repertoires are available that represent both the naive state (i.e. antigen-inexperienced) and that after immunization. This wealth of data has created opportunities to learn more about our immune system. In this review, we discuss the many ways in which BCR repertoire data have been or could be exploited. We highlight its utility for providing insights into how the naive immune repertoire is generated and how it responds to antigens. We also consider how structural information can be used to enhance these data and may lead to more accurate depictions of the sequence space and to applications in the discovery of new therapeutics.

SUBMITTER: Marks C

PROVIDER: S-EPMC7380193 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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How repertoire data are changing antibody science.

Marks Claire C Deane Charlotte M CM

The Journal of biological chemistry 20200514 29

Antibodies are vital proteins of the immune system that recognize potentially harmful molecules and initiate their removal. Mammals can efficiently create vast numbers of antibodies with different sequences capable of binding to any antigen with high affinity and specificity. Because they can be developed to bind to many disease agents, antibodies can be used as therapeutics. In an organism, after antigen exposure, antibodies specific to that antigen are enriched through clonal selection, expans ...[more]

PMID: 32409582

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Project description:Immunotherapy is becoming increasingly important in the fight against cancers, using and manipulating the body's immune response to treat tumors. Understanding the immune repertoire-the collection of immunological proteins-of treated and untreated cells is possible at the genomic, but technically difficult at the protein level. Standard protein databases do not include the highly divergent sequences of somatic rearranged immunoglobulin genes, and may lead to miss identifications in a mass spectrometry search. We introduce a novel proteogenomic approach, AbScan, to identify these highly variable antibody peptides, by developing a customized antibody database construction method using RNA-seq reads aligned to immunoglobulin (Ig) genes.AbScan starts by filtering transcript (RNA-seq) reads that match the template for Ig genes. The retained reads are used to construct a repertoire graph using the "split" de Bruijn graph: a graph structure that improves on the standard de Bruijn graph to capture the high diversity of Ig genes in a compact manner. AbScan corrects for sequencing errors, and converts the graph to a format suitable for searching with MS/MS search tools. We used AbScan to create an antibody database from 90 RNA-seq colorectal tumor samples. Next, we used proteogenomic analysis to search MS/MS spectra of matched colorectal samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) against the AbScan generated database. AbScan identified 1,940 distinct antibody peptides. Correlating with previously identified Single Amino-Acid Variants (SAAVs) in the tumor samples, we identified 163 pairs (antibody peptide, SAAV) with significant cooccurrence pattern in the 90 samples. The presence of coexpressed antibody and mutated peptides was correlated with survival time of the individuals. Our results suggest that AbScan (https://github.com/csw407/AbScan.git) is an effective tool for a proteomic exploration of the immune response in cancers.

Dataset Information

How repertoire data are changing antibody science.

Publications

How repertoire data are changing antibody science.

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