Of parts and relationships: An unending quest

Abstract

Systems biology is a field which focuses on the interpretation of large, diverse sets of biological measurements in order to elucidate the complex mechanisms that underly important and (seemingly simple) macroscopic phenotypes. The problem at hand is hierarchical in nature, with the hierarchy spanning many levels. Each of these levels can be thought of as comprising multiple active agents that are diverse in their nature (e.g. genes, proteins, pathways, organelles, etc) and also in their behavior. It is within this setting that one seeks to build an integrated view of the system under study, as soon as the relevant units and the complex inter- and intra-level relationships in which these units participate have been characterized. Implicit in the above outline are the assumptions that a) a complete and presumably correct list of parts exists for the system that is being studied; and, b) most, if not all, of the relevant relationships involving these parts are available. Through the research work of my group and of others, there is increasing evidence that the situation is likely to be more complicated than initially estimated, and that one should be watchful when it comes to making or relying on the above two assumptions. In fact, more surprising and currently undiscovered things may be lurking in the "genomics" box: support for this possibility will be provided through the brief summaries of recent advances that we have made in diverse areas such as association discovery, gene discovery, horizontal gene transfer and RNA interference. Throughout this quest, repositories of biological information will continue to remain our guiding light, whereas time-honored computational methods will continue to be the mainstay of our arsenal.