The Papenfuss laboratory uses mathematics, statistics and computing to make sense of cancer genome sequencing and other -omics data.
Mechanistic and functional drivers of neochromosome evolution
Neochromosomes are massive extra chromosomes that are stitched together from hundreds of pieces of normal chromosomes. They are rare overall – found in 3 per cent of cancers – but are common in some rare cancers, such as liposarcomas. We have mapped their structure and found that they form through punctuated chromosome shattering and gene amplification. This project will use whole genome sequencing with Illumina short-read and PacBio long-read technology, deep-targeted transcriptomic and epigenomic sequencing, and computational modelling to understand the functional and mechanistic pathways that underlie the dynamic process of neochromosome formation.
Methods for the identification of genomic rearrangements in tumour genomes
Genomic instability in cancers leads to large-scale rearrangements in tumour genomes. The detection of these rearrangements using Illumina short-read sequencing and other sequencing technologies remains a challenging problem. We are developing new methods that integrate de novo assembly and statistical models of quality to improve variant calling.
The evolution of metastatic melanoma and computational methods for cancer evolution
Samples collected in the CASCADE rapid autopsy program and xenograft experiments are providing profound new insights into the evolution of melanoma and other cancers. This requires the development of specialised analysis tools, including new pipelines for analysing multiple related samples; inference of the relationship between samples from multiple tumours and multi-regional sampling; and inference of subclonal heterogeneity of individual tumour samples.
Mofiz E, Seemann T, Bahlo M, Holt D, Currie BJ, Fischer K, Papenfuss AT (2016). The mitochondrial genome sequence of the scabies mite provides insight into the genetic diversity of individual scabies infections. PLOS Neglected Tropical Diseases.10(2):e0004384.
Garsed DW*, Marshall OJ*, Corbin VDA*, Hsu A*, Di Stefano L, Schröder J, Li J, Feng Z-P, Kim BW, Kowarsky M, Lansdell B, Brookwell R, Myklebost O, Meza-Zepeda L, Holloway AJ, Pedeutour F, Choo KHA, Damore MA, Deans AJ, Papenfuss AT**, Thomas DM** (2014). Architecture and Evolution of a Cancer Neochromosome. Cancer Cell. 26(5):653-67. (* joint first authors; ** joint last/corresponding authors)
Schroeder J, Hsu A, Boyle SE, MacIntyre G, Cmero M, Tothill RW, Johnstone RW, Shackleton M, Papenfuss AT (2014). Socrates: Identification of genomic rearrangements in tumour genomes by re-aligning soft clipped reads. Bioinformatics.30(8):1064-1072.
Li S*, Lefranc M-P*, Miles JJ*, Alamyar E, Giudicelli V, Duroux P, Freeman JD, Corbin V, Scheerlinck J-P, Frohman MA, Cameron PU, Plebanski M, Loveland B, Burrows SR, Papenfuss AT, Gowans EJ (2013). Next generation sequencing and IMGT/HighV-QUEST: a paradigm for T cell receptor IMGT clonotype diversity analysis and repertoire immunoprofiling. Nature Communications.4:2333.
Murchison EP, Tovar C, Hsu A, Bender HS, Kheradpour P, Rebbeck CA, Obendorf D, Conlan C, Bahlo M, Blizzard CA, Pyecroft S, Kreiss A, Kellis M, Stark A, Harkins TT, Marshall Graves JA, Woods GM, Hannon GJ, Papenfuss AT (2010). The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science.327(5961):84-87.