Epistasis Blog

From the Computational Genetics Laboratory at the University of Pennsylvania (www.epistasis.org)

Thursday, March 29, 2012

Is Life Law-Like?

This is a must read for those of you interested in epistasis and biological complexity. Fabulous paper.

Weiss KM, Buchanan AV. Is life law-like? Genetics. 2011 Aug;188(4):761-71. [PubMed]


Genes are generally assumed to be primary biological causes of biological phenotypes and their evolution. In just over a century, a research agenda that has built on Mendel's experiments and on Darwin's theory of natural selection as a law of nature has had unprecedented scientific success in isolating and characterizing many aspects of genetic causation. We revel in these successes, and yet the story is not quite so simple. The complex cooperative nature of genetic architecture and its evolution include teasingly tractable components, but much remains elusive. The proliferation of data generated in our "omics" age raises the question of whether we even have (or need) a unified theory or "law" of life, or even clear standards of inference by which to answer the question. If not, this not only has implications for the widely promulgated belief that we will soon be able to predict phenotypes like disease risk from genes, but also speaks to the limitations in the underlying science itself. Much of life seems to be characterized by ad hoc, ephemeral, contextual probabilism without proper underlying distributions. To the extent that this is true, causal effects are not asymptotically predictable, and new ways of understanding life may be required.

Wednesday, March 07, 2012

Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges

Great new paper on pathway analysis. Must read.

Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol. 2012 Feb;8(2):e1002375. [PLoS]


Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge baseā€“driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis.