Alignment free identification of clones in B cell receptor repertoires

Ofir Lindenbaum, Nima Nouri, Yuval Kluger, Steven H. Kleinstein

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Following antigenic 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: (i) grouping sequences based on shared V and J gene assignments, and junction lengths and (ii) clustering these sequences using a junction-based distance. However, this approach is sensitive to the initial 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 junction-based distance method, it also identifies clones with characteristics (multiple V or J gene assignments or junction lengths) that are not detectable with the junction-based distance method.

Original languageEnglish
Article numbere21
JournalNucleic Acids Research
Issue number4
StatePublished - 26 Feb 2021
Externally publishedYes

Bibliographical note

Funding Information:
NIH [R01 AI104739 to S.H.K., R01 HG008383 to Y.K., R01 GM131642 to Y.K., R01 GM135928 to Y.K., P50 CA121974 to Y.K., T15LM007056 to N.N.]. Funding for open access charge: NIH [R01 AI104739].

Publisher Copyright:
© 2021 The Author(s) 2020.


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