Biocom LifeLines Magazine Feature: “Illuminating unknowns in the dynamic interplay of genetics, environment, and disease”

Spurred by the advent of massively parallel, next-generation sequencing, our ability to interrogate the genome at scale across large populations has now identified hundreds to thousands of genetic variants associated with virtually every disease. As these discoveries have emerged, it has also become clear that genetics represents only a fraction of the total story, in essence serving as a ‘probabilistic’ barometer for disease, rather than a ‘deterministic’ indicator of disease risk. Complementing genetic risk are the thousands of key modulators and exposures that occur over a person’s lifetime.

Central to these modulators are the dynamic measures of pathway activation, cellular function, and organ-level physiology that serve as indicators of real-time health status. Indeed, during an annual physical at the doctor’s office, two tubes of blood are drawn and from that biological sample, a dozen to several dozen dynamic non-genetic biomarkers are assayed—from metabolites to proteins to inorganic ions—and used to drive disease diagnoses, implement therapeutic strategies, and monitor overall health.

While they are a mainstay of modern medicine, these several dozen dynamic markers represent less than 0.1 percent of the total molecules circulating in human blood. The next stage of drug discovery and development will largely depend on our ability to move beyond the genome to capture, measure, and make sense of the 99.9 percent of dynamic, non-genetic biomarkers that to date have remained unexplored.