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The collection of immunoglobulin genes in an individuals germline, which gives rise to B cell receptors via recombination, is known to vary significantly across individuals. In humans, for example, each individual has only a fraction of the several hundred known V alleles. Furthermore, the currently-accepted set of known V alleles is both incomplete (particularly for non-European samples), and contains a significant number of spurious alleles. The resulting uncertainty as to which immunoglobulin alleles are present in any given sample results in inaccurate B cell receptor sequence annotations, and in particular inaccurate inferred naive ancestors. In this paper we first show that the currently widespread practice of aligning each sequence to its closest match in the full set of IMGT alleles results in a very large number of spurious alleles that are not in the samples true set of germline V alleles. We then describe a new method for inferring each individuals germline gene set from deep sequencing data, and show that it improves upon existing methods by making a detailed comparison on a variety of simulated and real data samples. This new method has been integrated into the partis annotation and clonal family inference package, available at https://github.com/psathyrella/partis, and is run by default without affecting overall run time.
We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in
B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same clonal family) are released
The development of single-cell technologies provides the opportunity to identify new cellular states and reconstruct novel cell-to-cell relationships. Applications range from understanding the transcriptional and epigenetic processes involved in meta
Naive human T cells are produced in the thymus, which atrophies abruptly and severely in response to physical or psychological stress. To understand how an instance of stress affects the size and diversity of the peripheral naive T cell pool, we deri
Motivation: Bisulphite sequencing enables the detection of cytosine methylation. The sequence of the methylation states of cytosines on any given read forms a methylation pattern that carries substantially more information than merely studying the av