The Bioinformatics group works on the analysis of next-generation sequencing (NGS) sequencing data and its research and clinical applications, particularly with respect to cancer. Cancer is increasingly being viewed as a disease where the tissue of origin is less important therapeutically than the unique spectrum of mutations found in the individual patient’s tumour.
Next-generation sequencing (NGS) is the key technology used to catalogue mutations in both DNA and RNA and while it has been a research staple for over 5 years, it is only now starting to make inroads into the clinic. NGS is a high-throughput genomics technology with significant computational and storage requirements – the data for each tumour/normal sample pair can up to half a terabyte of disk to store and tens of thousands of CPU hours to analyse.
The absence of standardised cluster hardware and analysis workflows has been a key factor keeping NGS in a research setting and out of hospitals and pathology departments and the Bioinformatics group is working on methodologies to address that deficit.
The team originally came together as part of Australia’s International Cancer Genomics Consortium (ICGC) effort, sequencing and analysing over 500 samples from pancreatic and ovarian cancer patients. The Australian team has submitted more cancer sequencing data to ICGC than any other member nation apart from the USA.
NGS cancer techniques
- Somatic variant calling from tumour/normal DNA comparison including SNVs, small indels, structural variants and copy number changes
- In silico validation of variants using RNA and other sequencing types
- Pathogen screening
- Telomere quantification
Quek K et al. A workflow to increase verification rate of chromosomal structural rearrangements using high-throughput next-generation sequencing. Biotechniques. 2014 Jul 1;57(1):31-8. [http://www.ncbi.nlm.nih.gov/pubmed/25005691]
Kassahn KS et al. Somatic point mutation calling in low cellularity tumors. PLoS One. 2013 Nov 8;8(11):e74380. [http://www.ncbi.nlm.nih.gov/pubmed/24250782]
Chou A et al. Clinical and molecular characterization of HER2 amplified-pancreatic cancer. Genome Med. 2013 Aug 31;5(8):78 [http://www.ncbi.nlm.nih.gov/pubmed/24004612]
Alexandrov LB et al. Signatures of Mutational Processes in Human Cancer. (2013) Nature Aug 22;500(7463):415-21 [http://www.ncbi.nlm.nih.gov/pubmed/23945592]
Gonzalez-Perez A et al. Computational Approaches to Identify Functional Genetic Variants in Cancer Genomes (2013) Nature Methods Jul 30;10(8);723-9. [http://www.ncbi.nlm.nih.gov/pubmed/23900255]
Biankin AV et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. (2012). Nature Nov 15;491(7424):399-405. [http://www.ncbi.nlm.nih.gov/pubmed/23103869]
Song S et al. qPure: A Tool to Estimate Tumor Cellularity from Genome-wide Single-Nucleotide Polymorphism Profiles. (2012). PloS One 7(9). [http://www.ncbi.nlm.nih.gov/pubmed/23049875]
Cowley MJ et al. PINA v2.0: mining interactome modules. (2012). Nucleic Acids Research 40:D862-5. [http://www.ncbi.nlm.nih.gov/pubmed/22067443]
Wood DL et al. X-MATE: a flexible system for mapping short read data. (2011). Bioinformatics 27(4), 580-1. [http://www.ncbi.nlm.nih.gov/pubmed/21216778]
Robbins CM et al. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. (2011). Genome Res 21(1), 47-55. [http://www.ncbi.nlm.nih.gov/pubmed/21147910]
The 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. (2010) Nature 467, 1061-1073. [http://www.ncbi.nlm.nih.gov/pubmed/20981092]
The International Cancer Genome Consortium. International network of cancer genome projects. (2010) Nature 464, 993-998. [http://www.ncbi.nlm.nih.gov/pubmed/20393554]
Webster JA et al. Genetic control of human brain transcript expression in Alzheimer disease. (2009) Am J Hum Genet 84(4), 445-58. [http://www.ncbi.nlm.nih.gov/pubmed/19361613]
Craig DW et al. Identification of genetic variants using bar-coded multiplexed sequencing. (2008) Nature Methods 5(10), 887-93. [http://www.ncbi.nlm.nih.gov/pubmed/18794863]
Homer N et al. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. (2008). PLoS Genet 4(8):e1000167 [http://www.ncbi.nlm.nih.gov/pubmed/18769715]
Homer N et al. Multimarker analysis and imputation of multiple platform pooling-based genome-wide association studies. (2008). Bioinformatics 24(17), 1896-902. [http://www.ncbi.nlm.nih.gov/pubmed/18617537]
Myers AJ et al. A survey of genetic human cortical gene expression. (2007) Nat Genet 39(12), 1494-9. [http://www.ncbi.nlm.nih.gov/pubmed/17982457]
Beckstrom-Sternberg SM et al. Complete Genomic Characterization of a Pathogenic A.II Strain of Francisella tularensis Subspecies tularensis. (2007) PLoS ONE 2(9):e947. [http://www.ncbi.nlm.nih.gov/pubmed/17895988]
Dunckley T et al. Whole-Genome Analysis of Sporadic Amyotrophic Lateral Sclerosis. (2007) N Engl J Med 357(8), 775-88. [http://www.ncbi.nlm.nih.gov/pubmed/17671248]
Melquist S et al. Identification of a novel risk locus for Progressive Supranuclear Palsy by a pooled genome-wide scan of 500,288 SNPs. (2007) American Journal of Human Genetics 80(4), 769-778. [http://www.ncbi.nlm.nih.gov/pubmed/17357082]
Pearson JV et al. Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. (2007) American Journal of Human Genetics 80(1), 126-39. [http://www.ncbi.nlm.nih.gov/pubmed/17160900]
Papassotiropoulos A et al. Common Kibra alleles are associated with human memory performance. (2006). Science 314(5798), 475-8. [http://www.ncbi.nlm.nih.gov/pubmed/17053149]
Gillanders EM et al. The value of molecular haplotypes in a family-based linkage study. (2006) American Journal of Human Genetics 79, 458-68. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559540/]
Huentelman et al. SNiPer: improved SNP genotype calling for Affymetrix 10K GeneChip microarray data. (2005) BMC Genomics 6, 149. [http://www.ncbi.nlm.nih.gov/pubmed/16262895]
Pollock PM et al. Compilation of Somatic Mutations of the CDKN2 Gene in Human Cancers: Non-Random Distribution of Base Substitutions. (1996) Genes, Chromosomes & Cancer 15, 77-88. [http://www.ncbi.nlm.nih.gov/pubmed/8834170]
If you wish to apply for QIMR Berghofer's student program,
click here for more information.