Personal genome: data analysis challenge

Five themes emerged from the material presented at the 3rd annual personal genomes meeting at Cold Spring Harbor Laboratory held September 10-12, 2010.

First was the trend of family sequencing becoming more of a norm; looking at genetic disease as it is represented in trios, quartets or other family groups.

Second was the trend of increasingly common multi-level analysis, investigating traditional genotype data together with structural variation, expression data, pathways, and cell lines.

Third was the trend of greater breadth and sophistication in cancer genome analysis; the fledgling field of a few years ago now including dozens of sequenced cancer tumor genomes, the first cancer methylome, and cancer transcriptome analysis.

Fourth was the trend of the oft-heard challenge of scaling personal genome interpretation, making it automated, affordable, and actionable.

The fifth theme was the continued improvement in genome sequencing technology through new approaches such as quantum dot nanocrystal sequencing and strobe sequencing.

Unified health data climate

The future of health management and biosecurity is having always-on access to the health data climate of individuals, families, communities, and countries. A whole new era of health awareness and self-management could be possible. Ideally, health data streams would be automatically captured and parsed into a comprehensive tableau of status monitoring and action-taking.

Key health data streams (Figure 1):

1. Genome - whole human genome sequence, abnormal tissue sequences (cancer, etc.)
2. Phenotype - current status of a wide range of biophysical markers including blood-based organ-secreted proteins prognosticating disease, cholesterol levels, blood pressure, and emotional state
3. Diseasome - catalog of cumulative immune system exposures and predicted response to toxins
4. Microbiome - microflora bacteria profile (gut, genital, skin, oral, etc.)
5. Environmentome - external environment measures including air and water quality, pollen/allergens count

Figure 1: Key health data streams.

So discontinuous a discontinuity

A key aspect of thinking systemically about the future is being able to see how rapidly advancing technologies across many fields interrelate. Whatever next Internet-like discontinuity or singularity occurs will influence whatever comes thereafter. It is likely that some high percentage of what are now thought to be expected future advances will recede or be reshaped at minimum, for example:

• If all chronic disease and aging becomes controllable and there is effective immortality, does uploading matter as much?
• If artificial general intelligence is achieved, how does that change the exigency and requirements of molecular nanotechnology?
• If affordable space launch and space-based solar power is achieved, what happens to ethanol, electrical and other terrestrial alternative vehicle and transportation infrastructure solutions?
• If immersive virtual reality and post-material scarcity are achieved, does molecular nanotechnology matter and what happens to global political systems?
• If whole human genome testing is available, do single SNP tests go away? If there are home health monitors and nanodiagnostics, do primary care physicians go away?

Gene Encyclopedia of all Life

A tremendous resource would be an open gene database of all of the genes present in eukaryotic, archaeal and bacterial life. There are several open genomic databases now but the information is organized around genomes and organisms rather than specific genes and gene function.

A gene database of all life is in the same vein as E.O. Wilson’s Encyclopedia of Life, but at the next level of detail. The Encyclopedia of Life hopes to provide a webpage with scientific information for every known species on Earth. The gene database would provide a webpage and scientific details for each gene present in life and include other information such as a cross reference to all of the different species in which the gene is expressed.

Merge the Entrez Genome Project and the PartsRegistry
The foundations and perhaps the vision and obviousness of a gene database of all life exist but not its targeted pursuit as a funded research priority. Existing genomics databases such as the U.S. NCBI’s Entrez Genome Project database could be extended and merged into one database that is more explicitly searchable by gene function, possibly joining forces with the PartsRegistry from synthetic biology which provides a homepage, datasheet and genomic sequence by gene or biological function.

NCBI’s Entrez Genome Project database genomic catalog of all life

Unifying the work of E.O. Wilson, Craig Venter, Penny Boston and Drew Endy
An interesting project would be the unification of the Encyclopedia of Life, genomics-by-organism databases and parts registry-by-gene databases together with the aggressive pursuit of cataloguing and sequencing newly discovered organisms and genes. A gene encyclopedia could rapidly extend human knowledge and facilitate the era of personalized medicine as these novel genes could have extensive application in human therapies and pharmaceuticals, energy, climate management, agriculture and other areas.

Tremendous novelty and diversity remains unstudied with species (E.O. Wilson), with organisms in the sea (Craig Venter), and with extremophile life in caves (Penny Boston); 70-90% novel organisms, most of which have not had any gene identification and sequencing, functional assessment and cataloging.

A data resource like a gene encyclopedia could also uplevel the research focus to analytics. It will be interesting to see if an era of fully fungible genes across life arises, how easy it is to transplant function and how function expresses differently in different life forms.