Thursday, October 13, 2011

Personalities of Personal Genomes

"People say they want their genetic information, but they don’t." "The speaker's views of data return are frankly repugnant." These were some of the [paraphrased] comments and tweets expressed during Cold Spring Harbor's fourth annual conference entitled "Personal Genomes" held Sep 30 - Oct 2, 2011. The focus of which was to explore the latest technologies and approaches for sequencing genomes, exomes, and transcriptomes in the context of how genome science is, and will be, impacting clinical care. 

The future may be close than we think

In previous years, the concept of personal genome sequencing as a way to influence medical treatment was a vision. Last year, the reality of the vision was evident through a limited number of examples. This year, several new examples were presented along with the establishment of institutional programs for genomic-based medicine. The driver being the continuing decreases in data collection costs combined with corresponding access to increasing amounts of data. According to Richard Gibbs (Baylor College of Medicine) we will have close to 5000 genomes completely sequenced by the end of this year and by the end of 2012, 30,000 complete genome sequences are expected.

The growth of genome sequencing is now significant  enough that leading institutions are also beginning to establish guidelines for genomics-based medicine. Hence, an ethics panel discussion was held during the conference. The conversation about how DNA sequence data may be used has been an integral discussion since the beginning of the Genome Project. Indeed James Watson shared his lament for having to fund ethics research and directly asked the panel if they have done any good. There was a general consensus, from the panel, and audience members who have had their genomes sequenced, that ethics funding has helped by establishing genetic counseling and eduction practices.  

However, as pointed out by some audience members, this ethics panel, like many others, focused too heavily on the risks for individuals and society having their genomic data. In my view, the discussion would have been more interesting and balanced if the panel included the individuals who are working outside of institutions with new approaches  for understanding health. Organizations like 23andMe, Patients LIke Me, or the Genetic Alliance bring a very different and valuable perspective to the conversation.

Ethics was a fraction of the conference. The remaining talks at were organized into six sessions that covered personal cancer genomics, medically actionable genomics, personal genomes, rare diseases, and clinical implementations of personal genomics. The key messages from these presentations and posters was that, while genomics-based medical approaches have demonstrated success, much more research needs to be done before such approaches are mainstream.  

For example, in the case of cancer genomics, whole genome sequences from tumor and normal cells can give a picture of point mutations and structural rearrangements, but these data need to be accompanied by exome sequences to get the high read depth needed to accurately detect the low levels of rare mutations that may be disregulating cell growth or conferring resistance to treatment. Yet, the resulting profiles of variants are still inadequate to fully understand the functional consequences of the mutations. For this, transcriptome profiling is needed, and that is just the start.  

Once the data are collected they need to be processed in different ways, filtered, and compared within and between samples. Information from many specialized databases will be used in conjunction with statistical analyses to develop insights that can be validated through additional assays and measurements.  Finally, a lab seeking to do this work, and return results back to patients, will also need to be certified, minimally by CLIA standards.  For many groups this is significant undertaking, and good partners with experience and strong capabilities like PerkinElmer will be needed. 

Further Reading

Nature Coverage, Oct 6 issue:
Genomes on prescription
Other news and information: