Dr Warren Kaplan, Bioinformatics Analyst at Garvan's Peter Wills Bioinformatics Centre, developed new techniques to analyse the microarray data. "We designed a computer program which used a 'sliding window' a window that computationally moves along the genome, noting the number of genes inside that window and how many of them are downregulated," he said.
"Some of the microarrays we used only measured mRNA or the level of gene expression. Others measured the overall methylation status of the genes in that same region. It was an opportunity for us to examine the genome in a multi-layered way."
Once Kaplan had provided an initial map, Drs Marcel Coolen and Clare Stirzaker and Jenny Song from Professor Clark's lab found a way to treat and analyse prostate cancer cells, allowing their comparative DNA methylation and chromatin states analysis against the microarray data.
Bioinformaticians within the Clark lab, Aaron Statham and Dr Mark Robinson, then developed novel methodologies to interpret resulting data essentially tens of millions of numbers. "It was like cracking a code," said Aaron. "At first the data made no sense."
Professor Clark emphasises the importance of developing the new genome technology and knowhow that allows analysis of epigenetic processes.
"There is so much we still don't know," she said. "Already we have an idea of the complexity and how it might impact on the specific drug combinations that you will have to use to reactivate genes, non-coding RNAs and microRNAs within these cancer-affected regions."
"Now that we have a prostate cancer epigenome map, our next step will be to understand the mechanism that's driving the chromatin reduction, or genome reduction within these 'lean mean machines'. In other words, what's the link between the genetics and the epigenetics?"
|Contact: Alison Heather|