Medical Biology - Research Publications

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    Socrates: identification of genomic rearrangements in tumour genomes by re-aligning soft clipped reads
    Schroeder, J ; Hsu, A ; Boyle, SE ; Macintyre, G ; Cmero, M ; Tothill, RW ; Johnstone, RW ; Shackleton, M ; Papenfuss, AT (OXFORD UNIV PRESS, 2014-04-15)
    MOTIVATION: Methods for detecting somatic genome rearrangements in tumours using next-generation sequencing are vital in cancer genomics. Available algorithms use one or more sources of evidence, such as read depth, paired-end reads or split reads to predict structural variants. However, the problem remains challenging due to the significant computational burden and high false-positive or false-negative rates. RESULTS: In this article, we present Socrates (SOft Clip re-alignment To idEntify Structural variants), a highly efficient and effective method for detecting genomic rearrangements in tumours that uses only split-read data. Socrates has single-nucleotide resolution, identifies micro-homologies and untemplated sequence at break points, has high sensitivity and high specificity and takes advantage of parallelism for efficient use of resources. We demonstrate using simulated and real data that Socrates performs well compared with a number of existing structural variant detection tools. AVAILABILITY AND IMPLEMENTATION: Socrates is released as open source and available from http://bioinf.wehi.edu.au/socrates CONTACT: papenfuss@wehi.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
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    Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene
    Lefebure, M ; Tothill, RW ; Kruse, E ; Hawkins, ED ; Shortt, J ; Matthews, GM ; Gregory, GP ; Martin, BP ; Kelly, MJ ; Todorovski, I ; Doyle, MA ; Lupat, R ; Li, J ; Schroeder, J ; Wall, M ; Craig, S ; Poortinga, G ; Cameron, D ; Bywater, M ; Kats, L ; Gearhart, MD ; Bardwell, VJ ; Dickins, RA ; Hannan, RD ; Papenfuss, AT ; Johnstone, RW (NATURE PUBLISHING GROUP, 2017-03-06)
    The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor. Moreover, we find unexpected concomitant multigenic lesions involving Cdkn2a loss and other cancer genes including Nras, Kras and Bcor. These findings challenge the assumed two-hit model of Eμ-Myc lymphoma and demonstrate a functional in vivo role for Bcor in suppressing tumorigenesis.