Simpathica: A Computational Systems Biology Tool Within the Valis Bioinformatics Environment

ABSTRACT Biology thrives on complexity, and yet our approaches to deciphering complex biological systems have been simple, observational, reductionist, and qualitative. The observational nature of biology may even seem self-evident, as expressed more than three centuries ago by Robert Hooke, whose work Micrographia of 1665 contained his microscopical investigations that included the first identification of biological cells: “The truth is, the science of Nature has already been too long made only a work of the brain and the fancy. It is now high time that it should return to the plainness and soundness of observations on material and obvious things.” As we begin to observe, infer, and list the fundamental “parts” out of which biology is created, we cannot stop marveling at how these same components and their variants and homologues interconnect, intertwine, and interact via universal principles that still remain to be fully deciphered. To unravel this biological complexity, of which we only have a hint so far, it has become necessary to develop novel tools and approaches that augment and rigorously formalize those human reasoning processes—tools that until now could be used for only tiny toy-like subsystems in biology. To this end, the anticipated computational systems biology tools aim to draw upon constructive mathematical approaches developed in the context of dynamical systems, kinetic analysis, computational theory, and logic. The resulting toolkit aspires to build powerful simulation, analysis, and reasoning facilities that can be used by working biologists for multiple purposes: in making sense of existing data, in devising new experiments, and ultimately in understanding functional properties of genomes, proteomes, cells, organs, and organisms. If this ambitious program is to ultimately succeed, there are certain critical components that require special attention of computer scientists and applied mathematicians. This chapter studies the nature of these components, software architecture for integrating them, and illustrative examples of how such an integrated system may function in practice.