Mar 31, 2020

Alignment free identification of clones in B cell receptor repertoires

BioRxiv : the Preprint Server for Biology
O. LindenbaumSteven Kleinstein

Abstract

Following pathogenic challenge, activated B cells rapidly expand and undergo somatic hypermutation, yielding groups of clonally related B-cells with diversified immunoglobulin receptors. Inference of clonal relationships based on the receptor sequence is an essential step in many adaptive immune receptor repertoire sequencing studies. These relationships are typically identified by a multi-step process that involves: (1) grouping sequences based on shared V and J gene assignments, and junction lengths, and (2) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial V(D)J gene assignments, which are error-prone, and fails to identify clonal relatives whose junction length has changed through accumulation of indels. Through defining a translation-invariant feature space in which we cluster the sequences, we develop an alignment-free clonal identification method that does not require gene assignments and is not restricted to a fixed junction length. This alignment-free approach has higher sensitivity compared to a typical junction-based distance method without loss of specificity and PPV. While the alignment-free procedure identifies clones that are broadly consistent with the...Continue Reading

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Mentioned in this Paper

Basic Research
Genome
Genes
CRISPR-Cas Systems
Gene Editing
Drosophila
Plants, Transgenic
Site
Genomics
Knock-in

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