Abstract
The occurrence of chimeric transcripts has been reported in many cancer cells and seen as potential biomarkers and therapeutic targets. Modern high-throughput sequencing technologies offer a way to investigate individual chimeric transcripts and the systematic information of associated gene expressions about underlying genome structural variations and genomic interactions. The detection methods of finding chimeric transcripts from massive amount of short read sequence data are discussed here. Both assembly-based and alignment-based methods are used for the investigation of chimeric transcripts.
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References
Maher CA, Kumar-Sinha C, Cao X, Kalyana-Sundaram S, Han B, Jing X, Sam L, Barrette T, Palanisamy N, Chinnaiyan AM (2009) Transcriptome sequencing to detect gene fusions in cancer. Nature 458(7234):97–101. doi:10.1038/nature07638
de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR (1982) A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 300(5894):765–767
Barlund M, Monni O, Weaver JD, Kauraniemi P, Sauter G, Heiskanen M, Kallioniemi OP, Kallioniemi A (2002) Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer. Genes Chromosomes Cancer 35(4):311–317. doi:10.1002/gcc.10121
Mitelman F, Johansson B, Mertens F (2007) The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer 7(4):233–245. doi:10.1038/nrc2091
Meyerson M, Gabriel S, Getz G (2010) Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet 11(10):685–696. doi:10.1038/nrg2841
Kircher M, Heyn P, Kelso J (2011) Addressing challenges in the production and analysis of illumina sequencing data. BMC Genomics 12:382. doi:10.1186/1471-2164-12-382
Carrara M, Beccuti M, Lazzarato F, Cavallo F, Cordero F, Donatelli S, Calogero RA (2013) State-of-the-art fusion-finder algorithms sensitivity and specificity. Biomed Res Int 2013:340620. doi:10.1155/2013/340620
Chu HT, Hsiao WW, Chen JC, Yeh TJ, Tsai MH, Lin H, Liu YW, Lee SA, Chen CC, Tsao TT, Kao CY (2013) EBARDenovo: highly accurate de novo assembly of RNA-Seq with efficient chimera-detection. Bioinformatics 29(8):1004–1010. doi:10.1093/bioinformatics/btt092
Edgren H, Murumagi A, Kangaspeska S, Nicorici D, Hongisto V, Kleivi K, Rye IH, Nyberg S, Wolf M, Borresen-Dale AL, Kallioniemi O (2011) Identification of fusion genes in breast cancer by paired-end RNA-sequencing. Genome Biol 12(1):R6. doi:10.1186/gb-2011-12-1-r6
Kim D, Salzberg SL (2011) TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol 12(8):R72. doi:10.1186/gb-2011-12-8-r72
Wu TD, Watanabe CK (2005) GMAP: a genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics 21(9):1859–1875. doi:10.1093/bioinformatics/bti310
Okonechnikov K, Golosova O, Fursov M (2012) Unipro UGENE: a unified bioinformatics toolkit. Bioinformatics 28(8):1166–1167. doi:10.1093/bioinformatics/bts091
Nicorici D, Satalan M, Edgren H, Kangaspeska S, Murumagi A, Kallioniemi O, Virtanen S, Kilkku O (2014) FusionCatcher—a tool for finding somatic fusion genes in paired-end RNA-sequencing data. bioRxiv, Nov. 2014. doi:10.1101/011650
Ge H, Liu K, Juan T, Fang F, Newman M, Hoeck W (2011) FusionMap: detecting fusion genes from next-generation sequencing data at base-pair resolution. Bioinformatics 27(14):1922–1928. doi:10.1093/bioinformatics/btr310
Fan X, Abbott TE, Larson D, Chen K (2014) BreakDancer—identification of genomic structural variation from paired-end read mapping. Curr Protoc Bioinformatics 2014. doi:10.1002/0471250953.bi1506s45
Sboner A, Habegger L, Pflueger D, Terry S, Chen DZ, Rozowsky JS, Tewari AK, Kitabayashi N, Moss BJ, Chee MS, Demichelis F, Rubin MA, Gerstein MB (2010) FusionSeq: a modular framework for finding gene fusions by analyzing paired-end RNA-sequencing data. Genome Biol 11(10):R104. doi:10.1186/gb-2010-11-10-r104
Wang K, Singh D, Zeng Z, Coleman SJ, Huang Y, Savich GL, He X, Mieczkowski P, Grimm SA, Perou CM, MacLeod JN, Chiang DY, Prins JF, Liu J (2010) MapSplice: accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res 38(18), e178. doi:10.1093/nar/gkq622
McPherson A, Hormozdiari F, Zayed A, Giuliany R, Ha G, Sun MG, Griffith M, Heravi Moussavi A, Senz J, Melnyk N, Pacheco M, Marra MA, Hirst M, Nielsen TO, Sahinalp SC, Huntsman D, Shah SP (2011) deFuse: an algorithm for gene fusion discovery in tumor RNA-Seq data. PLoS Comput Biol 7(5):e1001138. doi:10.1371/journal.pcbi.1001138
Li Y, Chien J, Smith DI, Ma J (2011) FusionHunter: identifying fusion transcripts in cancer using paired-end RNA-seq. Bioinformatics 27(12):1708–1710. doi:10.1093/bioinformatics/btr265
Asmann YW, Hossain A, Necela BM, Middha S, Kalari KR, Sun Z, Chai H-S, Williamson DW, Radisky D, Schroth GP, Kocher J-PA, Perez EA, Thompson EA (2011) A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines. Nucleic Acids Res. doi:10.1093/nar/gkr362
Iyer MK, Chinnaiyan AM, Maher CA (2011) ChimeraScan: a tool for identifying chimeric transcription in sequencing data. Bioinformatics 27(20):2903–2904. doi:10.1093/bioinformatics/btr467
Francis RW, Thompson-Wicking K, Carter KW, Anderson D, Kees UR, Beesley AH (2012) FusionFinder: a software tool to identify expressed gene fusion candidates from RNA-Seq data. PLoS One 7(6), e39987. doi:10.1371/journal.pone.0039987
Piazza R, Pirola A, Spinelli R, Valletta S, Redaelli S, Magistroni V, Gambacorti-Passerini C (2012) FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery. Nucleic Acids Res 40(16), e123. doi:10.1093/nar/gks394
Wu J, Zhang W, Huang S, He Z, Cheng Y, Wang J, Lam TW, Peng Z, Yiu SM (2013) SOAPfusion: a robust and effective computational fusion discovery tool for RNA-seq reads. Bioinformatics 29(23):2971–2978. doi:10.1093/bioinformatics/btt522
Jia W, Qiu K, He M, Song P, Zhou Q, Zhou F, Yu Y, Zhu D, Nickerson ML, Wan S, Liao X, Zhu X, Peng S, Li Y, Wang J, Guo G (2013) SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data. Genome Biol 14(2):R12. doi:10.1186/gb-2013-14-2-r12
Li JW, Wan R, Yu CS, Co NN, Wong N, Chan TF (2013) ViralFusionSeq: accurately discover viral integration events and reconstruct fusion transcripts at single-base resolution. Bioinformatics 29(5):649–651. doi:10.1093/bioinformatics/btt011
Torres-Garcia W, Zheng S, Sivachenko A, Vegesna R, Wang Q, Yao R, Berger MF, Weinstein JN, Getz G, Verhaak RG (2014) PRADA: pipeline for RNA sequencing data analysis. Bioinformatics 30(15):2224–2226. doi:10.1093/bioinformatics/btu169
Beccuti M, Carrara M, Cordero F, Lazzarato F, Donatelli S, Nadalin F, Policriti A, Calogero RA (2014) Chimera: a Bioconductor package for secondary analysis of fusion products. Bioinformatics 30(24):3556–3557. doi:10.1093/bioinformatics/btu662
Fernandez-Cuesta L, Sun R, Menon R, George J, Lorenz S, Meza-Zepeda LA, Peifer M, Plenker D, Heuckmann JM, Leenders F, Zander T, Dahmen I, Koker M, Schottle J, Ullrich RT, Altmuller J, Becker C, Nurnberg P, Seidel H, Bohm D, Goke F, Ansen S, Russell PA, Wright GM, Wainer Z, Solomon B, Petersen I, Clement JH, Sanger J, Brustugun OT, Helland A, Solberg S, Lund-Iversen M, Buettner R, Wolf J, Brambilla E, Vingron M, Perner S, Haas SA, Thomas RK (2015) Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data. Genome Biol 16(1):7. doi:10.1186/s13059-014-0558-0
Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, Adiconis X, Fan L, Raychowdhury R, Zeng Q, Chen Z, Mauceli E, Hacohen N, Gnirke A, Rhind N, di Palma F, Birren BW, Nusbaum C, Lindblad-Toh K, Friedman N, Regev A (2011) Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol 29(7):644–652. doi:10.1038/nbt.1883
Robertson G, Schein J, Chiu R, Corbett R, Field M, Jackman SD, Mungall K, Lee S, Okada HM, Qian JQ, Griffith M, Raymond A, Thiessen N, Cezard T, Butterfield YS, Newsome R, Chan SK, She R, Varhol R, Kamoh B, Prabhu AL, Tam A, Zhao Y, Moore RA, Hirst M, Marra MA, Jones SJ, Hoodless PA, Birol I (2010) De novo assembly and analysis of RNA-seq data. Nat Methods 7(11):909–912. doi:10.1038/nmeth.1517
Schulz MH, Zerbino DR, Vingron M, Birney E (2012) Oases: robust de novo RNA-seq assembly across the dynamic range of expression levels. Bioinformatics 28(8):1086–1092. doi:10.1093/bioinformatics/bts094
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Chu, HT. (2016). Transcriptome Sequencing for the Detection of Chimeric Transcripts. In: Grützmann, R., Pilarsky, C. (eds) Cancer Gene Profiling. Methods in Molecular Biology, vol 1381. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3204-7_14
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DOI: https://doi.org/10.1007/978-1-4939-3204-7_14
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3203-0
Online ISBN: 978-1-4939-3204-7
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