Medical Biology - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/238

Filters

2014 - 2017 3
Reset filters

Settings
Statistics
Citations
Type: Journal Article × Author: Papenfuss, Anthony × Author: Li, Jason × Author: Doyle, Maria × Start date: 2010 × End date: 2019 ×

Search Results

Now showing 1 - 3 of 3
  • Item
    Thumbnail Image
    PathOS: a decision support system for reporting high throughput sequencing of cancers in clinical diagnostic laboratories
    Doig, KD ; Fellowes, A ; Bell, AH ; Seleznev, A ; Ma, D ; Ellul, J ; Li, J ; Doyle, MA ; Thompson, ER ; Kumar, A ; Lara, L ; Vedururu, R ; Reid, G ; Conway, T ; Papenfuss, AT ; Fox, SB (BIOMED CENTRAL LTD, 2017-04-24)
    BACKGROUND: The increasing affordability of DNA sequencing has allowed it to be widely deployed in pathology laboratories. However, this has exposed many issues with the analysis and reporting of variants for clinical diagnostic use. Implementing a high-throughput sequencing (NGS) clinical reporting system requires a diverse combination of capabilities, statistical methods to identify variants, global variant databases, a validated bioinformatics pipeline, an auditable laboratory workflow, reproducible clinical assays and quality control monitoring throughout. These capabilities must be packaged in software that integrates the disparate components into a useable system. RESULTS: To meet these needs, we developed a web-based application, PathOS, which takes variant data from a patient sample through to a clinical report. PathOS has been used operationally in the Peter MacCallum Cancer Centre for two years for the analysis, curation and reporting of genetic tests for cancer patients, as well as the curation of large-scale research studies. PathOS has also been deployed in cloud environments allowing multiple institutions to use separate, secure and customisable instances of the system. Increasingly, the bottleneck of variant curation is limiting the adoption of clinical sequencing for molecular diagnostics. PathOS is focused on providing clinical variant curators and pathology laboratories with a decision support system needed for personalised medicine. While the genesis of PathOS has been within cancer molecular diagnostics, the system is applicable to NGS clinical reporting generally. CONCLUSIONS: The widespread availability of genomic sequencers has highlighted the limited availability of software to support clinical decision-making in molecular pathology. PathOS is a system that has been developed and refined in a hospital laboratory context to meet the needs of clinical diagnostics. The software is available as a set of Docker images and source code at https://github.com/PapenfussLab/PathOS .
  • Item
    Thumbnail Image
    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.
  • Item
    Thumbnail Image
    Bioinformatics Pipelines for Targeted Resequencing and Whole-Exome Sequencing of Human and Mouse Genomes: A Virtual Appliance Approach for Instant Deployment
    Li, J ; Doyle, MA ; Saeed, I ; Wong, SQ ; Mar, V ; Goode, DL ; Caramia, F ; Doig, K ; Ryland, GL ; Thompson, ER ; Hunter, SM ; Halgamuge, SK ; Ellul, J ; Dobrovic, A ; Campbell, IG ; Papenfuss, AT ; McArthur, GA ; Tothill, RW ; Calogero, RA (PUBLIC LIBRARY SCIENCE, 2014-04-21)
    Targeted resequencing by massively parallel sequencing has become an effective and affordable way to survey small to large portions of the genome for genetic variation. Despite the rapid development in open source software for analysis of such data, the practical implementation of these tools through construction of sequencing analysis pipelines still remains a challenging and laborious activity, and a major hurdle for many small research and clinical laboratories. We developed TREVA (Targeted REsequencing Virtual Appliance), making pre-built pipelines immediately available as a virtual appliance. Based on virtual machine technologies, TREVA is a solution for rapid and efficient deployment of complex bioinformatics pipelines to laboratories of all sizes, enabling reproducible results. The analyses that are supported in TREVA include: somatic and germline single-nucleotide and insertion/deletion variant calling, copy number analysis, and cohort-based analyses such as pathway and significantly mutated genes analyses. TREVA is flexible and easy to use, and can be customised by Linux-based extensions if required. TREVA can also be deployed on the cloud (cloud computing), enabling instant access without investment overheads for additional hardware. TREVA is available at http://bioinformatics.petermac.org/treva/.