Analysis of B cell antibody repertoires from next-generation sequencing (in autoimmunity and other diseases)
Tuesday, October 23rd, 2018
1:00 p.m. Room 202 MRB
Professor Steven H. Kleinstein
Department of Pathology, Yale School of Medicine, New Haven, CT, USA
Next-generation sequencing (NGS) technologies have revolutionized our ability to carry out large-scale adaptive immune receptor repertoire sequencing (AIRR-Seq) experiments. AIRR-Seq is increasingly being applied to profile B cell receptor (BCR) repertoires and gain insights into immune responses in healthy individuals and those with a range of diseases. As NGS technologies improve, these experiments are producing ever larger datasets, with tens- to hundreds-of-millions of BCR sequences. Although promising, repertoire-scale data present fundamental challenges for analysis requiring the development of new techniques and the rethinking of existing methods that are not scalable to the large number of sequences being generated . To address these challenges, we have developed computational tools and methods that we currently make available to the wider scientific community through the Immcantation tool suite (http://immcantation.org). This includes: raw read processing, novel V gene allele detection, subject-specific germline genotype identification, B cell clone assignment, lineage tree construction and analysis, somatic mutation profiling and selection analysis. Along with the underlying computational methodology, this presentation will discuss applications of BCR repertoire sequencing and lineage analysis to infection (HIV and West Nile Virus), vaccination (Influenza), autoimmunity (Multiple sclerosis, Myasthenia Gravis) and allergy/asthma.
1. Yaari G, Kleinstein SH. Practical guidelines for B-cell receptor repertoire sequencing analysis.
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