DNA Methylation Biomarkers
Our research is focused on identifying DNA methylation changes associated with disease, in order to improve interpretation of diagnostic samples and guide treatment decisions.
Our current focus is on prostate cancer. In our most recent project we used whole genome sequencing technologies to characterise the distinct methylome of cells surrounding the prostate tumour. Excitingly we identified a subset of methylation changes shared by both tumour cells and surrounding cells in the tumour microenvironment. These shared changes hold promise to improve the diagnostic and prognostic sensitivity of biopsies.
In a new project, funded by Cancer Council NSW, we are working with clinicians to explore the utility of our prostate microenvironment methylation biomarkers to determine the presence of multi-focal tumours. The aim is to establish a test of patient suitability for focal therapy, a promising new form of treatment than is less aggressive than current surgical approaches in which the whole prostate is removed.
The group has also played a role in developing methods to measure DNA methylation. In particular in devising analytical methods and workflows for the analysis of DNA methylation microarray data, and it’s integration with sample-matched data from other next-generation sequencing technologies measuring gene expression (RNA-seq) and chromatin modifications (ChIP-seq). In ongoing work we are also optimising the laboratory work and bioinformatic analysis of targeted bisuflite sequencing in formalin-fixed biopsy samples.
Pidsley R*, Lawrence M*, Zotenko E, Niranjan B, Statham A, Song J, Chabanon R, Qu W, Wang H, Richards M, Nair S, Armstrong N, Nim H, Papargiris M, Balanathan P, French H, Peters T, Norden S, Ryan A, Pedersen J, Kench J, Daly R, Horvath L, Stricker P, Frydenberg M, Taylor R, Stirzaker C, Risbridger G*, Clark S*. (2018) Enduring Epigenetic Landmarks Define the Cancer Microenvironment. Genome Research doi: 10.1101/gr.229070.117
Pidsley R*, Zotenko E*, Peters T, Lawrence M, Risbridger G, Molloy P, van Djik S, Muhlhausler B, Stirzaker C*, Clark S*. (2016) Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biology 17:208 doi: 10.1186/s13059-016-1066-1
Lim A, Wong N, Pidsley R, Zotenko E, Corry J, Dobrovic A, Clark S, Rischin D, Solomon B. (2016) Genome-scale methylation assessment did not identify prognostic biomarkers in oral tongue carcinomas. Clinical Epigenetics 10.1186/s13148-016-0235-0
Pidsley R, Viana J, Hannon E, Spiers H, Troakes C, Al-Sarraj S, Mechawar N, Turecki G, Schalkwyk L, Bray N, Mill J. (2014) Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia. Genome Biology 15 (10), 483 doi:10.1186/s13059-014-0483-2
Pidsley R*, Viana J*, Troakes C, Spiers H, Wong CCY, Safa A, Craig I, Schalkwyk L, Mill J. (2014) Epigenomic and transcriptomic signatures of 47,XXY karyotype in the brain. Epigenetics 1:9(4):587-99. doi: 10.4161/epi.27806
Pidsley R*, Wong CCY *, Volta M, Lunnon K, Mill J, Schalkwyk L. (2013) A data-driven approach to preprocessing Illumina 450k methylation array data. BMC Genomics 14:293 doi:10.1186/1471-2164-14-293
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Staff in the Group