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:

Secrets of the human genome disclosed

Nature readers flirt with genomics 

Genomes on prescription
Other news and information:

At CSHL conference, researchers highlight importance of RNA-seq data to guide cancer treatment

Personal Genomes 2011 Meeting Site

Conference Tweets

21st Century Medicine: A Question of Ps

Last Sunday and Monday (5/15, 5/16/11) the Institute for Systems Biology (ISB) held their annual symposium. This year was the 10th annual and focused on "Systems Biology and P4 Medicine."

For those new to P4 medicine, the Ps stand for Personalized, Predictive, Preventative, and Participatory. P4 medicine is about changing our current disease oriented, reactive, approaches to those that prevent disease by increasing the predictive power of diagnostics. Because we are all different, future diagnostics need to be tailored to each individual, which also means individuals need to be more aware of their health and proactively participate in their health care. The vision of P4 medicine is that it will not only dramatically improve the quality of health care, it will significantly decrease health care costs. Hence, some folks add additional Ps to include payment and policy.

P4 medicine is an ambitious goal. In Lee Hood's closing notes he noted four significant challenges that need to be overcome to make P4 medicine a practical reality:

1. IT challenges. In addition to working on how to transform datasets containing billions of measurements into actionable information, we need to integrate high dimensional data a wide variety of measurement systems. Reduced data will need to be presented in medical records that can be easily accessed and understood by health care providers and participants.
2. Education. Students, scientists, doctors, individuals, and policy makers need to learn and develop an understanding of how the networks of interacting proteins and biochemicals that make us healthy or sick are regulated by our genomes and respond to environmental factors. 
3. Big vs Small Science. Funding agencies are concerned with how to best support the research needed to create the kinds of technologies and approaches that will unlock biology's complexity to develop future diagnostics and efficacious therapies. Large-scale projects conducted over the past 10 years have made it clear that biology is extremely complex. Deciphering this complexity requires that we integrate production-orientated data collection approaches, that develop a data infrastructure, with focused research projects, run by domain experts, that explore specific ideas.  The challenge is balancing big and small science to achieve high impact goals. 
4. Families. Understanding the genetic basis of health and disease requires the research be conducted on samples derived from families rather than randomized populations. Many families are needed to develop critical insights. However, in the U.S. our IRB (Institutional Review Boards) are considered a hinderance to enrolling individuals. 

Through the day and half conference numerous presentations explored different aspects of the above challenges. Walter Jessen at Biomarker Commons has created excellent summaries of the first and second day's presentations. For those who like raw data, the #ISB2011P4 hashtag can be used to get the symposium's tweets.