Steven H. Kleinstein
Associate Professor of Pathology, Yale School of Medicine
Wednesday, October 24, 2018 @ 2:00pm
Room 1242, CSE Building
Analysis of B cell antibody repertoires from next-generation sequencing (in autoimmunity and other diseases)
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. Genome Med. 2015 Nov 20;7:121. doi: 10.1186/s13073-015-0243-2.
Dr. Steven Kleinstein is a computational immunologist with a combination of “big data” analysis and immunology domain expertise. He is currently an Associate Professor in the Department of Pathology and Department of Immunobiology at the Yale School of Medicine. He is a member of the Human and Translational Immunology program, the Yale Center for Medical Informatics and the Interdepartmental Program for Computational Biology and Bioinformatics. Dr. Kleinstein’s research interests include both developing new computational methods and applying these methods to study human immune responses. Somatic hypermutation (SHM) and B cell affinity maturation, the core of adaptive immunity, have been a particular focus of his work, with a major emphasis on large-scale B cell receptor repertoire analysis (AIRR-Seq). His lab makes available the widely-used Immcantation framework (http://immcantation.org), which provides a start-to-finish analytical ecosystem for AIRR-Seq analysis.