title: Reference-free prediction of rearrangement breakpoint reads.
abstract: BACKGROUND
  Chromosome rearrangement events are triggered by atypical breaking and rejoining of DNA molecules, which are observed in many cancer-related diseases. The detection of rearrangement is typically done by using short reads generated by next-generation sequencing (NGS) and combining the reads with knowledge of a reference genome. Because structural variations and genomes differ from one person to another, intermediate comparison via a reference genome may lead to loss of information.
  
  
  RESULTS
  In this article, we propose a reference-free method for detecting clusters of breakpoints from the chromosomal rearrangements. This is done by directly comparing a set of NGS normal reads with another set that may be rearranged. Our method SlideSort-BPR (breakpoint reads) is based on a fast algorithm for all-against-all comparisons of short reads and theoretical analyses of the number of neighboring reads. When applied to a dataset with a sequencing depth of 100×, it finds ∼ 88% of the breakpoints correctly with no false-positive reads. Moreover, evaluation on a real prostate cancer dataset shows that the proposed method predicts more fusion transcripts correctly than previous approaches, and yet produces fewer false-positive reads. To our knowledge, this is the first method to detect breakpoint reads without using a reference genome.
  
  
  METHODS
  The source code of SlideSort-BPR can be freely downloaded from https://code.google.com/p/slidesort-bpr/.
authors.affiliation: Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Edward
authors.initials: E
authors.lastname: Wijaya
authors.affiliation: Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asai
authors.affiliation: Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 and Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1, Okubo Shinjuku-ku, Tokyo 169-8555, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Hamada
mesh_terms: D000465:Algorithms; D056905:Chromosome Breakpoints; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA; D012984:Software; D014178:Translocation, Genetic / Q000235:genetics*