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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Discrimination of germline V genes at different sequencing lengths and mutational burdens: A new tool for identifying and evaluating the reliability of V gene assignment
Journal of immunological methods, v 427, pp 105-116
Dec 2015
PMID: 26529062
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Immune repertoires are collections of lymphocytes that express diverse antigen receptor gene rearrangements consisting of Variable (V), (Diversity (D) in the case of heavy chains) and Joining (J) gene segments. Clonally related cells typically share the same germline gene segments and have highly similar junctional sequences within their third complementarity determining regions. Identifying clonal relatedness of sequences is a key step in the analysis of immune repertoires. The V gene is the most important for clone identification because it has the longest sequence and the greatest number of sequence variants. However, accurate identification of a clone's germline V gene source is challenging because there is a high degree of similarity between different germline V genes. This difficulty is compounded in antibodies, which can undergo somatic hypermutation. Furthermore, high-throughput sequencing experiments often generate partial sequences and have significant error rates. To address these issues, we describe a novel method to estimate which germline V genes (or alleles) cannot be discriminated under different conditions (read lengths, sequencing errors or somatic hypermutation frequencies). Starting with any set of germline V genes, this method measures their similarity using different sequencing lengths and calculates their likelihood of unambiguous assignment under different levels of mutation. Hence, one can identify, under different experimental and biological conditions, the germline V genes (or alleles) that cannot be uniquely identified and bundle them together into groups of specific V genes with highly similar sequences.
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Details
- Title
- Discrimination of germline V genes at different sequencing lengths and mutational burdens: A new tool for identifying and evaluating the reliability of V gene assignment
- Creators
- Bochao Zhang - Drexel UniversityWenzhao Meng - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 405B Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USAEline T. Luning Prak - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 405B Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USAUri Hershberg - Drexel University
- Publication Details
- Journal of immunological methods, v 427, pp 105-116
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000367127100015
- Scopus ID
- 2-s2.0-84952637427
- Other Identifier
- 991019167709104721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Immunology