Developing a better alignment tool for VDJ recombined sequences
Autor: | Chia-HungChu, 朱家弘 |
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Rok vydání: | 2013 |
Druh dokumentu: | 學位論文 ; thesis |
Popis: | 101 T-cell receptor (TCR) can recognize antigen presented by major histocompatibility complex (MHC) and activate immune reactions. To recognize numerous antigens, T-cell receptor undergoes VDJ recombination for diverse structures. In addition to its vital roles in immune response, VDJ recombination has been implicated in disease diagnosis and vaccination. It is thus important to identify correct VDJ recombination for recombined TCR sequences by aligning them to the TCR genes. Because TCR genes contain a lot of repeats, common alignment tools are not suitable. As a result, new tools like SoDA and IMGT/HighV-Quest, have been recently proposed to align recombined TCR sequences. On several datasets, we found that some alignments by these tools were still not satisfying because the alignment identities were low. This motivated us to develop a better alignment tool, called TCR-Aligner. TCR-Aligner integrates several computational methods, e.g., BLAST local alignment, global alignment, and depth-first-search algorithm, to improve accuracy and sensitivity for aligning recombined TCR sequences. On our 454 TCRB datasets, TCR-Aligner aligned 84.51% recombined TCR sequences to the TCR gene higher than SoDA and IMGT/HighV-Quest (48.31% and 36.80%) did, respectively. More importantly, TCR-Aligner achieved higher alignment accuracy than other tools. The better performance of TCR-Aligner remained on three other datasets of distinct natures. Because VDJ recombination is essential in immune system, TCR-Aligner should directly benefit scientists in this field. |
Databáze: | Networked Digital Library of Theses & Dissertations |
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