Conference Summary

Past, Present, and Future of Personalized Medicine

Jacquelyn K. Beals, PhD


December 11, 2009

In This Article

The topic of personalized medicine and its implications for the future practice of medicine were highlighted at the American Society of Human Genetics (ASHG) 59th Annual Meeting in the Presidential Symposium entitled "Implementing Personalized Medicine," which was hosted by 2009 ASHG President Edward R.B. McCabe, MD, PhD,[1] Co-Director of the University of California Los Angeles Center for Society and Genetics.

"Genome sequencing is only one part of genetic information and must be supplemented by information from epigenomics and transcriptomics," noted Dr. McCabe in his opening remarks. To be predictive and diagnostic at a personal level, personalized medicine requires association data from diverse populations and must include personalized therapeutic strategies. The 4 speakers at the Symposium were asked to "explore the challenges as well as progress in the implementation of personalized medicine."

Systems Medicine, Transformational Technologies, and the Emergence of P4 Medicine

"Systems medicine works under the premise that disease arises as a consequence of perturbed networks," noted Lee Hood, MD, PhD,[2] Co-Founder and Director of the Institute for Systems Biology in Seattle, Washington. Massive data sets generated from the information in the genome contain information impinged on by the environment; biological networks integrate these data to understand better the development and progression of disease. A systems biology approach toward medicine might include:

  • Doing global analysis -- looking at genes, mRNA, and proteins;

  • Integrating multiscalar data types and dealing with signal-to-noise issues in data sets;

  • Looking at network dynamics;

  • Using a hypothesis-driven approach -- working from model to hypothesis to perturbations, to integrate different types of data into the model; and

  • Generating models that are predictive and actionable.

Giving an example of how this approach might be implemented, Dr. Hood reviewed some of the work being done in mice to understand prion disease. Mice of 8 inbred strains were infected with prion disease, and their brains were examined to see which genes changed as a result of disease. The study narrowed the number of potentially involved genes, then focused on 4 disease-related mechanisms: prion infection and replication, degeneration of nerve cell extremities, microglial activation, and nerve cell death.

Six weeks after infection, no clinical signs or infectious prions were seen in the brain. However, by 10 weeks, infectious prions were replicating and accumulating in the brain; maximal change was seen 20 weeks after infection.

Two thirds of the disease-involved genes were associated with 1 of the 4 major disease pathogenic networks, but one third encoded novel pathogenic networks: "the dark genes of prion disease." Identifying these genes suggested ways that drugs could be used to reengineer disease-perturbed networks and provided insight into a systems' approach to diagnostics. Most important, proteins appeared in the blood as the prion disease was developing and could be diagnostic as early as 10 weeks, before infection was obvious.

Each of the many proteins secreted into the blood reflects the activity of its biological network. Thus, changes in protein levels reflect dynamic changes in the networks -- analysis of these brain-specific proteins provides a profile of the disease and can be valuable in searching for drug targets and understanding disease progression.

Dr. Hood suggested that the future of systems medicine will allow us to:

  • Use single-cell analyses for genomes, transcriptomes (ie, all of the RNA transcripts produced by the genome a specific time), and microRNA-omes as well as the proteome, interactions, localizations, and multiplex analyses;

  • Sequence 1000 transcriptomes simultaneously in a DNA sequencing run from single cancer cells;

  • Develop 50 proteins from 50 organs as part of a wellness assessment;

  • Analyze 10,000 B cells and 10,000 T cells for immune receptors, and analyze individual stem cells from each individual for use in neurodegenerative and other diseases; and

  • Use organ-specific blood-protein fingerprints to study interactions of multiple organs in therapeutic responses, drug toxicity, and biology using disease-perturbed networks as a method of identifying drug targets and assessing drugs used in individuals for toxicity, response, and dosage.

Stretching from statistical analysis of massive data sets to genomic analysis of a single cell, the systems view of disease plus the new technologies will lead to what Dr. Hood called "P4 medicine" -- medicine that is predictive, personalized, preventive, and participatory. With P4 medicine, the availability of longitudinal data on hundreds of millions of patients will help us better understand both disease development and therapeutic response in ways that are impossible in reactive medicine.


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