Assigning and visualizing germline genes in antibody repertoires

Simon D. W. Frost, Ben Murrell, A. S. Md. Mukarram Hossain, Gregg J. Silverman, Sergei L. Kosakovsky Pond
2015 Philosophical Transactions of the Royal Society of London. Biological Sciences  
One contribution of 13 to a theme issue 'The dynamics of antibody repertoires'. Identifying the germline genes involved in immunoglobulin rearrangements is an essential first step in the analysis of antibody repertoires. Based on our prior work in analysing diverse recombinant viruses, we present IgSCUEAL (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a phylogenetic approach to assign V and J regions of immunoglobulin sequences to their corresponding germline alleles,
more » ... h D regions assigned using a simple pairwise alignment algorithm. We also develop an interactive web application for viewing the results, allowing the user to explore the frequency distribution of sequence assignments and CDR3 region length statistics, which is useful for summarizing repertoires, as well as a detailed viewer of rearrangements and region alignments for individual query sequences. We demonstrate the accuracy and utility of our method compared with sequence similarity-based approaches and other non-phylogenetic model-based approaches, using both simulated data and a set of evaluation datasets of human immunoglobulin heavy chain sequences. IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing approaches, even when the reassorted sequence is highly mutated, and can successfully cluster sequences on the basis of shared V/J germline alleles. L 1 J 6 * 0 1 J 6 * 0 2 J 6 * 0 3 J 6 * 0 4 1000 V3,J6 (61.15%) V gene J allele all rearrangements V family
doi:10.1098/rstb.2014.0240 pmid:26194754 pmcid:PMC4528417 fatcat:d7ybn2675vfmdc3sh6mp7xsbze