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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing

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sumrep: A Summary Statistic Framework for Immune Receptor Repertoire Comparison and Model Validation.

Branden J Olson^1,2, Pejvak Moghimi³, Chaim A Schramm⁴

¹Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Frontiers in Immunology

|November 19, 2019

Summary

Analyzing adaptive immune receptor repertoire sequencing (AIRR-seq) data is challenging. The sumrep R package simplifies analysis, revealing that V(D)J recombination deletion/insertion lengths better characterize repertoires than CDR3 amino acid composition.

Keywords:

B cell receptor T cell receptor model validation rep-seq repertoire comparison summary statistics

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Area of Science:

Immunology
Bioinformatics
Computational Biology

Background:

The adaptive immune system generates diverse B and T cell receptors to combat pathogens.
Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data offers insights but is complex to analyze.
Current analysis methods struggle with the intricate structure of AIRR-seq datasets.

Purpose of the Study:

Introduce sumrep, an R package for efficient analysis and comparison of AIRR-seq data.
Evaluate the utility of various repertoire summaries for distinguishing biological covariates.
Assess the performance of generative models in recapitulating AIRR-seq data characteristics.

Main Methods:

Development and application of the sumrep R package for repertoire summarization and comparison.
Analysis of AIRR-seq datasets to compare different summary statistics.
Validation of generative models against experimental AIRR-seq data.

Main Results:

The sumrep package facilitates diverse repertoire summaries and comparisons.
Deletion and insertion lengths from V(D)J recombination are more discriminative than CDR3 amino acid composition.
Generative models accurately capture gene usage and recombination statistics but not all physiochemical properties.

Conclusions:

The sumrep R package provides an efficient tool for analyzing complex AIRR-seq data.
V(D)J recombination features offer superior repertoire characterization compared to CDR3 amino acid summaries.
While generative models show promise, they require further development to fully capture real-world immune repertoire complexity.