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Albert Einstein and ESHG 2013- Day 2

Lucas Smink
| Jun 10, 2013
Illumina workshop at ESHG

Today was the first whole day of ESHG, with all-day sessions. In fact, with the Illumina workshop tonight, it was pretty much a 12-hour day of talks, and I set out to try and prove my perspective right and attend just the cancer sessions. I started off with the Gene Regulation in Cancer session featuring three interesting talks. The first two talks really focused on mutations and epimutations. Jean-Pierre Issa showed that DNA methylation is abnormal in cancer and showing both hypo and hyper methylation patterns suggest that cancer is an epigenetic disease, as mutations in cancer often affect epigenetic regulators. Nazneen Rahman from the Institute of Cancer Research filled up the session speaking about the clinical utility of cancer predisposition genes and her work in mainstreaming the cancer genetics program, also discussed in a previous blog post.

The other cancer session I attended was the Clinical Cancer Genetics club, the first talk by Pal Moller from Oslo really made a very good point for what Nazneen is doing in the UK. Professor Moller spoke about BRCA1 in breast cancer and the use of MRI for early diagnosis. His final conclusion being that annual MRI does nothing to reduce breast cancer mortality and that a genetic test is the only way to detect BRCA1, therefore, every woman should have the opportunity to have a BRCA1 test if they want to.

While NGS is a great solution, Mark Daly from the Broad Institute highlighted that in complex disease, gene discovery via sequencing isn’t easy. He highlighted that in complex disease, polygenicity is extreme as is the very high background of neutral variation so how do you home in on the right variants? Some ways of overcoming these challenges were to focus on the GWAS hits, the rare but interpretable categories of variation, as well as dramatically increase the sample size. For autism spectrum diseases, a large collaboration sponsored through NHGRI have committed to the exome sequencing of 2,000 trios, and the limiting factor so far has been the number of cases. He closed that the solution to unlocking complex disease was likely a combination of further GWAS studies as well as sequencing.

In the end the question is, what does all this variation do? The Functional Genomics session had a number of great talks looking at uncovering functional variation. Manolis Demitzakis spoke about the gEUVADIS project and using mRNA, microRNA, and WGS data from 500 individuals from the 1,000 genome project. His talk and the talks from Nahid Ahituv really highlighted that we have a ways to go in understanding the grammar of regulation. So what do Einstein and ESHG have to do with each other? One of the quotes attributed to Einstein is: “We still do not know one thousandth of one percent of what nature has revealed to us.” I guess that is why there are ~3,000 scientists in the Palais des Congrès sharing with each what they have learned about nature and how our knowledge is increasing, but there is still a ways to go.

My final session of the day was the Illumina workshop, and lots of people stayed with us to not only enjoy the wine and cheese but also the talks. Joel Fellis kicked it off with an update from Illumina, followed by Matt Huentelman from the Translational Genomics Research Institute. Dr. Huentelman spoke about his work in The Center for Rare Childhood Disorders and highlighted a number of cases they have been working on. He made a very interesting point that the perfect study design would be whole-genome sequence at 30x, combined with exome at 100x and mRNA sequence data.  Which, looking at the Functional Genomics session, is a real requirement for linking biology to human variation. Rich Shippy from Illumina finished the session talking about clinical offerings, including the cytoSNP-850K BeadChip which together with the BlueGnome BlueFuse software offers an integrated solution for cytogenomic relevant genes as well as for MiSeqDx with the Cystic Fibrosis assay.