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Activity Number:
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302
- Omics I
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Type:
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Contributed
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Date/Time:
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Tuesday, July 31, 2018 : 8:30 AM to 10:20 AM
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Sponsor:
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Biometrics Section
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Abstract #330605
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Title:
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Modeling Dynamics of V(D)J Recombination in T Cell Formation
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Author(s):
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Kingshuk Roy Choudhury*
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Companies:
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Duke University, Dept. of Biostatistics and Bioinformatics
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Keywords:
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VDJ recombination;
high througput sequencing;
T cell repertoire;
constrained Brownian motion;
numerical optimization;
statistical modelling
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Abstract:
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Our body produces a large variety or 'repertoire' (over 100000 variants) of T cells, enabling our immune system to recognize a wide variety of antigens and thus organize a response against them. V(D) J recombination is the mechanism by which this large variety of T cells are produced from a relatively small section of the genome. This section contains about 80 contiguous V D segments followed by about 50 contiguous J segments (exact numbers depend on the species). During T cell maturation, this section of the genome is edited to produce a combination of a particular V and J segments to create a particular 'signature' capable of recognizing a specific type of antigen. The mechanism of editing isn't well understood. To discover this process, we model data obtained from a novel screen of a T cell repertoire in wild type and mutant mice. The screen utilizes high throughput sequencing of T cell genomes to obtain the joint distribution of V-J combinations in the repertoire at a given time. We propose a constrained Brownian motion with linear drift model for the dynamics of V segment usage relative to J locus. The model is fit by numerical optimization and fits the mean and variance of th
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Authors who are presenting talks have a * after their name.
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