1. ImmunoTyper-SR: A computational approach for genotyping immunoglobulin heavy chain variable genes using short-read data
- Author
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Michael K.B. Ford, Ananth Hari, Oscar Rodriguez, Junyan Xu, Justin Lack, Cihan Oguz, Yu Zhang, Andrew J. Oler, Ottavia M. Delmonte, Sarah E. Weber, Mary Magliocco, Jason Barnett, Sandhya Xirasagar, Smilee Samuel, Luisa Imberti, Paolo Bonfanti, Andrea Biondi, Clifton L. Dalgard, Stephen Chanock, Lindsey B. Rosen, Steven M. Holland, Helen C. Su, Luigi D. Notarangelo, Uzi Vishkin, Corey T. Watson, S. Cenk Sahinalp, Kerry Dobbs, Elana Shaw, Miranda F. Tompkins, Camille Alba, Adelani Adeleye, Samuel Li, Jingwen Gu, Ford, M, Hari, A, Rodriguez, O, Xu, J, Lack, J, Oguz, C, Zhang, Y, Weber, S, Magliocco, M, Barnett, J, Xirasagar, S, Samuel, S, Imberti, L, Bonfanti, P, Biondi, A, Dalgard, C, Chanock, S, Rosen, L, Holland, S, Su, H, Notarangelo, L, Vishkin, U, Watson, C, and Sahinalp, S
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genomic ,ILP ,next generation sequencing ,algorithm ,computational biology ,Histology ,genotyping ,immunogenomic ,Cell Biology ,immunoglobulin ,optimization ,WGS ,Pathology and Forensic Medicine - Abstract
Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.
- Published
- 2022
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