Exploring the Role of Variation in Defining Phenotype and Disease

November 2011

The history of biomedical research has been driven by one basic and extraordinarily successful question: Given a measurement for an experimental and a control group, is the average difference between groups large relative to the variance? While this has allowed us to discover elements that are activated or deactivated during development and disease progression, and in different tissues and organs, it fails to capture the entire spectrum of changes that occur as cells change from one state to another.

There is a second, equally important question one might ask: For a biologically relevant pathway or mechanism, is there a large difference in the variance exhibited by different phenotypic groups? It may be that, in fact, the difference in the mean captures the features of the steady state of different phenotypes, while the variance captures the more dynamic nature of cell-fate transitions.

Recent work by our group and others has brought new attention to the importance of the variation in defining biological systems, transforming our understanding of cellular systems and providing new ways of understanding the processes that control the way cells change state and differentiate.

We propose to bring together the leaders in this new and transformative area of biological research to explore opportunities to advance the field through collaborative research projects. One concrete deliverable from this meeting will be a white paper on the importance of studying the link between variance and phenotype to be submitted to a major academic journal.