RNA-Seq Mapping and Detection of Gene Fusions with a Suffix Array Algorithm
| العنوان: | RNA-Seq Mapping and Detection of Gene Fusions with a Suffix Array Algorithm |
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| المؤلفون: | Sowmi Utiramerur, Milan Radovich, Jeffrey K. Ichikawa, Yongzhi Chen, Fiona Hyland, Kelli Bramlett, Paolo Vatta, Vidya Kudlingar, Liviu Popescu, Heinz Breu, Yulei N. Wang, Robert C. Nutter, P. Whitley, Asim S. Siddiqui, Nriti Garg, Matthew W. Muller, Benjamin S. Kong, John Bodeau, Catalin Barbacioru, Zheng Zhang, Joel Brockman, Onur Sakarya, Chieh-Yuan Li, Jian Gu |
| المصدر: | PLoS Computational Biology PLoS Computational Biology, Vol 8, Iss 4, p e1002464 (2012) |
| بيانات النشر: | Public Library of Science, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Sequence analysis, Molecular Sequence Data, RNA-Seq, Biology, Computer Applications, Fusion gene, Cellular and Molecular Neuroscience, Exon, Genome Analysis Tools, Genetics, Genomic library, Molecular Biology, Gene, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, Oligonucleotide Array Sequence Analysis, Ecology, Base Sequence, Sequence Analysis, RNA, Intron, Computational Biology, Genomics, Computational Theory and Mathematics, lcsh:Biology (General), Modeling and Simulation, RNA splicing, Computer Science, Gene Fusion, Algorithms, Software, Research Article |
| الوصف: | High-throughput RNA sequencing enables quantification of transcripts (both known and novel), exon/exon junctions and fusions of exons from different genes. Discovery of gene fusions–particularly those expressed with low abundance– is a challenge with short- and medium-length sequencing reads. To address this challenge, we implemented an RNA-Seq mapping pipeline within the LifeScope software. We introduced new features including filter and junction mapping, annotation-aided pairing rescue and accurate mapping quality values. We combined this pipeline with a Suffix Array Spliced Read (SASR) aligner to detect chimeric transcripts. Performing paired-end RNA-Seq of the breast cancer cell line MCF-7 using the SOLiD system, we called 40 gene fusions among over 120,000 splicing junctions. We validated 36 of these 40 fusions with TaqMan assays, of which 25 were expressed in MCF-7 but not the Human Brain Reference. An intra-chromosomal gene fusion involving the estrogen receptor alpha gene ESR1, and another involving the RPS6KB1 (Ribosomal protein S6 kinase beta-1) were recurrently expressed in a number of breast tumor cell lines and a clinical tumor sample. Author Summary Advances in sequencing technology are enabling detailed characterization of RNA transcripts from biological samples. The fundamental challenge of accurately mapping the reads on transcripts and gleaning biological meaning from the data remains. One class of transcripts, gene fusions, is particularly important in cancer. Some gene fusions are prominent markers in leukemia, prostate, and other cancers and putatively causative in certain tumor types. We present a set of new RNA-Seq analysis techniques to map reads, and count expression of genes, exons and splicing junctions, especially those that give evidence of gene fusions. These tools are available in a software package with a straightforward graphical user interface. Using this software, we called and validated several gene fusions in a breast cancer cell line. By testing the presence of these fusions in a larger population of tumor cell lines and clinical samples, we found that two of them were expressed recurrently. |
| اللغة: | English |
| تدمد: | 1553-7358 1553-734X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eee026de4b4b245a7aad9b5db0532ae5 http://europepmc.org/articles/PMC3320572 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eee026de4b4b245a7aad9b5db0532ae5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537358 1553734X |
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