I recently attended the Human Genome Meeting (HGM2016) in Houston, TX and wanted to share some of the highlights from the meeting.
The overall focus of the meeting was the application of genomics to medicine, and the presentations were, without exception, excellent. There is no way I can possibly summarize all of the great science that was presented at the meeting, but I’d like to focus on some general themes that emerged.
Looking beyond disease drivers
One of the most prominent scientific themes I noticed at the meeting was a shift from identifying frequent recurrent pathogenic mutations to a need to better understand the genomic context in which a disease-causing mutation occurs. For example, Nicholas Katsanis‘s talk “One plus one equals zero” focused on cases where apparently deleterious mutations can be beneficial, depending on the other mutations present in the individual. He also spoke about the need to cautiously interpret evolutionary conservation, as sometimes deleterious mutations in humans are actually the fixed wild-type variant in other species (and vice-versa). Peter Campbell (along with several other speakers) talked about the “long tail” of cancer mutations—the observation that there are few highly recurrent mutations in a given tumor type and a large number of very rare mutations (for many kinds of cancer). It therefore “doesn’t make sense to talk about a BRAF+ tumor” since most patients will have many mutations. There is a strong need to understand how the mutations interact to affect treatment outcome and survival.
Patient-centric approaches to precision medicine
This point is intimately connected to—and follows from—the first theme. If patients have multiple mutations (even in the case of “monogenic” diseases), then we need to understand individual patients and not just broadly-defined diseases. However, this theme was much larger than just patient-centric modeling of disease. Most speakers talked about the need to put patients at the center of their own diagnosis and treatment and to make them partners in the whole process. This is also a major theme of the US Precision Medicine Initiative. Maynard Olson kicked off the meeting with a fabulous historical perspective of genomics with a view to the future. He talked about how the current way of approaching medical research is to put the PI at the center of the project, with funding agencies, institutions, IRBs, patients, etc. as interacting entities. The future of medical research should be to have the patient (or research subject) as the center. To accomplish this, we need trusted intermediaries between patients/research subjects. Researchers and research subjects should have a sense of ownership of their data. For more on the issue of trust, I highly recommend this PLoS Biology paper by Yaniv Erlich et al. “Redefining Genomic Privacy: Trust and Empowerment.” Similar sentiments were shared by multiple speakers, including Kay Davies, Peter Campbell, Catherine Brownstein, Levi Garraway, Ian Campbell, Lynda Chin…and many others. Abstracts of all the talks are available at the HGM2016 website.
‘Info commons’ data sharing
This was another huge, overarching theme that was mentioned, in some way, in nearly every presentation. Medical research has traditionally been done within individual, separate medical institutes. However, patients benefit most when information is shared globally because it accelerates discovery of disease-causal gene variants and potential targeted therapeutics. There was a focus on how technology can lead to better data sharing and, ultimately, improved patient care. For example, Peter Campbell talked about building knowledge banks, using shared clinical data, for specific diseases that will allow precision modeling of diseases and treatment options tailored to individual patients. Another example came from Thomas Hudson, who spoke about how cloud computing can support sharing of very large datasets and coordinate legal and ethical oversight of data access.
An entire session was devoted to Ethical, Legal and Social Implications (ELSI) of global information commons for medical research. The big picture takeaway is that getting global sharing of clinical data is hard, because each country has different laws and regulations regarding privacy and informed consent. A key goal is to identify globally acceptable minimum standards as a starting point. Beyond the legal issues, there are also difficulties in convincing researchers to share unpublished (and often even published) data. Funding agencies, scientific societies, research institutions and journal publishers all have a role to play in this (for our part, see our recent editorials on data access and peer review in the cloud; both are links to free-to-read PDFs). Charles Rotimi gave a really excellent overview of the H3Africa initiative during this session, and reminded us that there are other issues to consider. In this case, the fact that African samples have long been used for research by non-Africans requires sensitivity when discussing data release from African countries (and other developing countries). The H3Africa initiative seeks to build genomics research infrastructure within Africa through research conducted by African scientists, with our without international collaborators. This shift will require longer time periods between data generation and data release, in order to give African researchers—those who are generating the data—time to analyze their data and publish. Thus, a one-size-fits-all solution to data access is not the right approach.
The second half of the last day of the meeting was devoted to talks by award recipients. The two Chen Investigator awards for 2016 were awarded to Feng Zhang (New Investigator award) and Bing Ren (Award for Distinguished Academic Achievement). Feng Zhang gave an overview of the CRISPR-Cas9 gene editing technology and gave a preview of the new CRISPR enzymes that have been recently discovered and how they might be used to improve the technology. Bing Ren talked about 3D genome organization and the many technological advances (many from his group) that have enabled a deeper understanding of how the genome is organized and how this organization regulates gene functions.
The final talk of the meeting was especially appropriate. Raj Ramesar received the HUGO African Prize for 2016 and he talked not only about his research, but also about the need to shift scientists’ outlook from a focus on individual prestige to a focus on what they can do to most benefit society. His talk was predominately about science in developing countries, but I think the sentiment is true for academia as a whole.
The overall tone of the meeting was one of excitement and possibility. The field of genomics, as Dr. Olson very nicely demonstrated in his talk, has been around for 30 years. But in some ways, it feels like this is only the beginning. Genomics has the potential to truly transform medicine and, from what I can tell, scientists and clinicians are ready and willing to to their part to make this transformation a reality.