Computational Challenges of Systems Biology the Role of Modeling

26 Computer Computational Challenges of Systems Biology B ioinformatics is the computing response to the molecular revolution in biology. This revolution has reshaped the life sciences and given us a deep understanding of DNA sequences, RNA synthesis, and the generation of proteins. In the process of achieving this revolution in understanding, we have accumulated vast amounts of data. The scale of this data, its structure, and the nature of the analytic task have merited serious attention from computer scientists and prompted work in intelligent systems, data mining, visualization, and more. It has also demanded serious efforts in large-scale data curation and developing a worldwide infrastructure to support this. Bioinformatics, the handmaiden of molecular biology, poses novel computational challenges, stretches the state of the art, and opens unanticipated uses of computing concepts. In tackling these, computer scientists have the additional satisfaction of contributing to a scientific Grand Challenge. Bioinformatics is, however, only the first step in reshaping the life sciences. For further progress, we must return to the study of whole biological systems: the heart, cardiovascular system, brain, and liver—systems biology. To build an integrated physiology of whole systems, we must combine data from the many rich areas of biological information. Alongside the genome, which constitutes our knowledge about genes, we place the proteome, metabolome, and physiome, which embody knowledge about proteins, metabolic processes, and physiology. Systems biology is at least as demanding as, and perhaps more demanding than, the genomic challenge that has fired international science and gained public attention. Progressing in this discipline will involve computer scientists working in close partnership with life scientists and mathematicians. In contrast to the molecular biology revolution, computer science will proactively engage in shaping the endeavor rather than just clearing up afterwards! The prize to be attained is immense. From in silico drug design and testing to individualized medicine that will take into account physiology and genetic profiles, systems biology has the potential to profoundly affect healthcare and medical science generally.