Dataset Information

Revealing individual signatures of human T cell CDR3 sequence repertoires with Kidera Factors.

ABSTRACT: The recent development of High Throughput Sequencing technologies has enabled an individual's TCR repertoire to be efficiently analysed at the nucleotide level. However, with unique clonotypes ranging in the tens of millions per individual, this approach gives a surfeit of information that is difficult to analyse and interpret in a biological context and gives little information about TCR structural diversity. Using publicly available TCR CDR3 sequence data, we analysed TCR repertoires by converting the encoded CDR3 amino acid sequences into Kidera Factors, a set of orthogonal physico-chemical properties that reflect protein structure. This approach enabled the TCR repertoire from different individuals to be distinguished and demonstrated the close similarity of the repertoire in different samples from the same individual.

SUBMITTER: Epstein M

PROVIDER: S-EPMC3906109 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Revealing individual signatures of human T cell CDR3 sequence repertoires with Kidera Factors.

Epstein Michael M Barenco Martino M Klein Nigel N Hubank Michael M Callard Robin E RE

PloS one 20140129 1

The recent development of High Throughput Sequencing technologies has enabled an individual's TCR repertoire to be efficiently analysed at the nucleotide level. However, with unique clonotypes ranging in the tens of millions per individual, this approach gives a surfeit of information that is difficult to analyse and interpret in a biological context and gives little information about TCR structural diversity. Using publicly available TCR CDR3 sequence data, we analysed TCR repertoires by conver ...[more]

PMID: 24489822

Similar Datasets

Project description:BackgroundDefensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF) genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics.ResultsWe find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34) which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes.ConclusionsComplexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans multisite variations as well as haplotypes by sequencing based methods is the way for future studies of interindividual DEF locus variability and its disease association.

Dataset Information

Revealing individual signatures of human T cell CDR3 sequence repertoires with Kidera Factors.

Publications

Revealing individual signatures of human T cell CDR3 sequence repertoires with Kidera Factors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets