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Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing
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Profiling immunoglobulin repertoires across multiple human tissues using RNA sequencing.

Igor Mandric1, Jeremy Rotman1,2, Harry Taegyun Yang1,3

  • 1Department of Computer Science, University of California, Los Angeles, 404 Westwood Plaza, Los Angeles, CA, 90095, USA.

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Summary

ImReP is a new computational method that profiles immunoglobulin (Ig) receptor repertoires from RNA sequencing data. This method generated the atlas of immunoglobulin repertoires (TAIR), a large resource for studying immune diseases.

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Area of Science:

  • Immunology
  • Bioinformatics
  • Genomics

Background:

  • Specialized assays for immunoglobulin (Ig) receptor repertoire profiling are often costly and time-consuming.
  • There is a need for efficient methods to analyze Ig repertoires across diverse human tissues.

Purpose of the Study:

  • To develop and validate ImReP, a computational tool for rapid and accurate profiling of Ig receptor repertoires.
  • To create the atlas of immunoglobulin repertoires (TAIR), a comprehensive dataset of Ig sequences from various human tissues.
  • To analyze Ig clonotype flow and inter-tissue similarities using the generated dataset.

Main Methods:

  • Utilized regular RNA sequencing data from the Genotype-Tissue Expression (GTEx v6) project, comprising 8,555 samples from 544 individuals.
  • Applied the ImReP computational method to profile immunoglobulin (Ig) receptor repertoires, including complementary-determining region 3 (CDR3) sequences.
  • Generated a large-scale dataset of 3.6 million Ig sequences, named the atlas of immunoglobulin repertoires (TAIR).

Main Results:

  • Successfully profiled Ig repertoires across 53 tissue types using ImReP and GTEx v6 data.
  • Generated TAIR, a collection of 3.6 million Ig sequences, expanding repertoire data to tissues with limited prior information.
  • Evaluated Ig clonotype dynamics and inter-tissue repertoire similarities, particularly in immune-related tissues.

Conclusions:

  • ImReP provides a rapid and cost-effective approach for Ig repertoire profiling using standard RNA sequencing data.
  • TAIR represents one of the largest available collections of CDR3 sequences and tissue types, serving as a valuable resource.
  • The findings facilitate the study of immunological diseases by providing insights into Ig repertoire diversity and tissue distribution.