title: A novel bioinformatics pipeline for identification and characterization of fusion transcripts in breast cancer and normal cell lines.
abstract: SnowShoes-FTD, developed for fusion transcript detection in paired-end mRNA-Seq data, employs multiple steps of false positive filtering to nominate fusion transcripts with near 100% confidence. Unique features include: (i) identification of multiple fusion isoforms from two gene partners; (ii) prediction of genomic rearrangements; (iii) identification of exon fusion boundaries; (iv) generation of a 5'-3' fusion spanning sequence for PCR validation; and (v) prediction of the protein sequences, including frame shift and amino acid insertions. We applied SnowShoes-FTD to identify 50 fusion candidates in 22 breast cancer and 9 non-transformed cell lines. Five additional fusion candidates with two isoforms were confirmed. In all, 30 of 55 fusion candidates had in-frame protein products. No fusion transcripts were detected in non-transformed cells. Consideration of the possible functions of a subset of predicted fusion proteins suggests several potentially important functions in transformation, including a possible new mechanism for overexpression of ERBB2 in a HER-positive cell line. The source code of SnowShoes-FTD is provided in two formats: one configured to run on the Sun Grid Engine for parallelization, and the other formatted to run on a single LINUX node. Executables in PERL are available for download from our web site: http://mayoresearch.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm.
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Yan W
authors.initials: YW
authors.lastname: Asmann
authors.forename: Asif
authors.initials: A
authors.lastname: Hossain
authors.forename: Brian M
authors.initials: BM
authors.lastname: Necela
authors.forename: Sumit
authors.initials: S
authors.lastname: Middha
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Kalari
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: High-Seng
authors.initials: HS
authors.lastname: Chai
authors.forename: David W
authors.initials: DW
authors.lastname: Williamson
authors.forename: Derek
authors.initials: D
authors.lastname: Radisky
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.forename: Jean-Pierre A
authors.initials: JP
authors.lastname: Kocher
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D005260:Female; D050939:Gene Fusion; D006801:Humans; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D012984:Software
chemical_list: D050506:Mutant Chimeric Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases