Dataset Information

Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies.

ABSTRACT: BACKGROUND: In the adaptive immune system, variable regions of immunoglobulin (IG) are encoded by random recombination of variable (V), diversity (D), and joining (J) gene segments in the germline. Partitioning the functional antibody sequences to their sourcing germline gene segments is vital not only for understanding antibody maturation but also for promoting the potential engineering of the therapeutic antibodies. To date, several tools have been developed to perform such "trace-back" calculations. Yet, the predicting ability and processing volume of those tools vary significantly for different sets of data. Moreover, none of them give a confidence for immunoglobulin heavy diversity (IGHD) identification. Developing fast, efficient and enhanced tools is always needed with the booming of immunological data. RESULTS: Here, a program named Ab-origin is presented. It is designed by batch query against germline databases based on empirical knowledge, optimized scoring scheme and appropriate parameters. Special efforts have been paid to improve the identification accuracy of the short and volatile region, IGHD. In particular, a threshold score for certain sensitivity and specificity is provided to give the confidence level of the IGHD identification. CONCLUSION: When evaluated using different sets of both simulated data and experimental data, Ab-origin outperformed all the other five popular tools in terms of prediction accuracy. The features of batch query and confidence indication of IGHD identification would provide extra help to users. The program is freely available at http://mpsq.biosino.org/ab-origin/supplementary.html.

SUBMITTER: Wang X

PROVIDER: S-EPMC2638160 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies.

Wang Xiaojing X Wu Di D Zheng Siyuan S Sun Jing J Tao Lin L Li Yixue Y Cao Zhiwei Z

BMC bioinformatics 20081212

<h4>Background</h4>In the adaptive immune system, variable regions of immunoglobulin (IG) are encoded by random recombination of variable (V), diversity (D), and joining (J) gene segments in the germline. Partitioning the functional antibody sequences to their sourcing germline gene segments is vital not only for understanding antibody maturation but also for promoting the potential engineering of the therapeutic antibodies. To date, several tools have been developed to perform such "trace-back" ...[more]

PMID: 19091020

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Project description:The adaptive immune system generates a remarkable range of antigen-specific T-cell receptors (TCRs), allowing the recognition of a diverse set of antigens. Most of this diversity is encoded in the complementarity determining region 3 (CDR3) of the ? chain of the ?? TCR, which is generated by somatic recombination of noncontiguous variable (V), diversity (D), and joining (J) gene segments. Deletion and non-templated insertion of nucleotides at the D-J and V-DJ junctions further increases diversity. Many of these gene segments are annotated as non-functional owing to defects in their primary sequence, the absence of motifs necessary for rearrangement, or chromosomal locations outside the TCR locus.We sought to utilize a novel method, based on high-throughput sequencing of rearranged TCR genes in a large cohort of individuals, to evaluate the use of functional and non-functional alleles. We amplified and sequenced genomic DNA from the peripheral blood of 587 healthy volunteers using a multiplexed polymerase chain reaction assay that targets the variable region of the rearranged TCR? locus, and we determined the presence and the proportion of productive rearrangements for each TCR? V gene segment in each individual. We then used this information to annotate the functional status of TCR? V gene segments in this cohort.For most TCR? V gene segments, our method agrees with previously reported functional annotations. However, we identified novel non-functional alleles for several gene segments, some of which were used exclusively in our cohort to the detriment of reported functional alleles. We also saw that some gene segments reported to have both functional and non-functional alleles consistently behaved in our cohort as either functional or non-functional, suggesting that some reported alleles were not present in the population studied.In this proof-of-principle study, we used high-throughput sequencing of the TCR? locus of a large cohort of healthy volunteers to evaluate the use of functional and non-functional alleles of individual TCR? V gene segments. With some modifications, our method has the potential to be extended to gene segments in the ?, ?, and ? TCR loci, as well as the genes encoding for B-cell receptor chains.

Dataset Information

Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies.

Publications

Ab-origin: an enhanced tool to identify the sourcing gene segments in germline for rearranged antibodies.

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