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At the Illumina Asia-Pacific Scientific Summit

Brett Kennedy
| Apr 30, 2013

A stellar lineup of international and local speakers presented across a range of topics from cancer, inherited disease to forensics and a thought-provoking set of microbial speakers. Even though I may decide to hang on during my next plane ride (more later), sequencing continues to excite as a tool to drive not only research but increasingly patient-focused questions.

Mike Snyder kicked things off with a synopsis of the latest ENCODE findings. While the recent publications from ENCODE and their significance have been widely discussed, Mike noted that it was estimated only 50% of regulatory elements have been discovered based on current modeling.

The link between Genome Wide Association Studies (GWAS) risk loci and ENCODE hits has been made, but analyses showing 56% of GWAS risk loci are in an LD block with ENCODE data highlight how correlated this association appears to be. Finally, Mike introduced the Regulome database as a tool to annotate personal genomes and to assist in exploring the impact of compound heterozygous regions in disease for which genome phasing information will be of critical value (Moleculo anyone?). 

David Bowtell spoke of ovarian cancer having four different types of response to therapy with many of the same drugs having been used to treat the disease for the last 30 years. However, using molecular analyses to identify the underlying biology of treatment response showed various genetic elements that could be used to understand the response and pursue new therapeutic options.

The major determinants to therapeutic response were identified as:

  1. Germline BRCA status1(should all women with ovarian cancer be tested for their BRCA status?)

  2. CCNE1 amplification (benefitted by PARP inhibitors)

  3. Molecular subtype present (outcomes relate to subtype)

  4. De-bulking status (relative success of surgical procedure)

These results echoed those of Sean Grimmond who showed that in their studies of pancreatic cancer for the ICGC, up to 20-25% of samples tested had a druggable mutation. For a disease with a very short progression from initial diagnosis, these are key discoveries. 

Ryan Taft from the IMB gave a very moving translational talk on taking a new path to his research when unexpectedly asked to help a child in need of a genetic diagnosis. Drawing from his work using next-generation sequencing to investigate non-coding RNAs, in the last year he managed to not only identify the cause of this child's disease, but also then extend this work to three additional sets of unresolved clinical cases! Importantly, these discoveries enabled some of the children to enroll in clinical trials, and, according to their parents, they have already shown improvements. 

The day then moved into Microdrive with a slew of talks highlighting the increasing understanding of the process and importance of microbes, both as individuals and communities in action. Peer Bork from EMBL made the link between microbes and cancer showing there were three main community types in normal Europeans, but those with colorectal cancer, Crohn’s disease, ulcerative colitis, and Type 2 diabetes all had distinct microbiota, most likely as a consequence of the disease. This may enable efforts at using microbiomes to diagnose difficult-to-detect diseases. 

Worryingly, the antibiotic resistance profiles of these human gut microbiomes also correlated with both personal antibiotic use in the last 12 months and the presence of antibiotic resistant isolates from abattoirs in the respective countries2. Most resistance genes seem to stay for at least 12 months from introduction. For those who want to join this research my.microbes has information on how to get your own personalized microbes report. Lastly, there is evidence that the microbiome can be modified, which opens up an exciting world of therapeutic potential. 

Stephan Schuster from NTU spoke about the amazing capability of 40-tonne sewage bioreactors to remove material that would otherwise cover the entire island of Singapore in 10 cm of odure per year! Correlating improved post-war health outcomes with the development of sewage treatment he points out that we actually don’t fully understand the organisms and processes that drive this amazing system.

Using the HiSeq 2500 with early access 2 x 250 bp chemistry in rapid run mode he was able to develop a 480 bp single-amplicon approach to create a metagenomic profile achieving 360 million reads from these 2-lane flow cells. They were able to identify 3 organisms responsible for nitrogen removal (present at less than 5% community abundance). Of the data generated, only 0.83% maps to known genomes with substantial plasmid transfer occurring but importantly virtually no viruses present. 

Finally, Shawn Levy of Hudson Alpha Institute spoke about how fecal transplants are proving to be a treatment option for C. difficile infections. This is becoming a bigger issue in children as ear infections though 75% viral are often treated with antibiotics that leave kids susceptible to colonization by this dangerous organism (rePOOPulate anyone?). Probiotics (bacteria in a capsule) may have some value during this process to help fill the niche of lost healthy gut flora and prevent colonization by harmful bacteria – more study is needed though. The only downside risk to these talks seems to be the ‘yuk’ factor – Shawn also tested the metagenome of airplane toilet door handles (from the inside). Good news was that it didn’t change all that much on a short internal US flight. I can’t wait to hear what happens on the longer international flights I tend to take! 

During the Day 2 breakout sessions, a wide range of talks were given in cancer, agrigenomics, genetic disease, microbial genomics along with Illumina general technical sessions and practical informatics seminars. We would like to thank our 37 speakers from 10 countries and attendees from 20 countries for their interest, time and participation. We look forward to another meeting of Illumina science and networking at the APAC Illumina Scientific Summit next year.

1. Alsop K., Fereday S, Meldrum C, deFazio A, Emmanuel C, et al. (2012) BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 30(21) 2654-63.

2. Forslund K, Sunagawa S, Kultima J, Mende D, Arumugam M, et al. (2013) Country-specific antibiotic use practices impact the human gut resistome. Genome Res. April.