Computational systems biology

Hiroaki Kitano
2002 Nature  
I t is often said that biological systems, such as cells, are 'complex systems' . A popular notion of complex systems is of very large numbers of simple and identical elements interacting to produce 'complex' behaviours. The reality of biological systems is somewhat different. Here large numbers of functionally diverse, and frequently multifunctional, sets of elements interact selectively and nonlinearly to produce coherent rather than complex behaviours. Unlike complex systems of simple
more » ... s, in which functions emerge from the properties of the networks they form rather than from any specific element, functions in biological systems rely on a combination of the network and the specific elements involved. For example, p53 (a 393-amino-acid protein sometimes called 'the guardian of genome') acts as tumour suppressor because of its position within a network of transcription factors. However, p53 is activated, inhibited and degraded by modifications such as phosphorylation, dephosphorylation and proteolytic degradation, while its targets are selected by the different modification patterns that exist; these are properties that reflect the complexity of the element itself. Neither p53 nor the network functions as a tumour suppressor in isolation. In this way, biological systems might be better characterized as symbiotic systems. Molecular biology has uncovered a multitude of biological facts, such as genome sequences and protein properties, but this alone is not sufficient for interpreting biological systems. Cells, tissues, organs, organisms and ecological webs are systems of components whose specific interactions have been defined by evolution; thus a system-level understanding should be the prime goal of biology. Although advances in accurate, quantitative experimental approaches will doubtless continue, insights into the functioning of biological systems will not result from purely intuitive assaults. This is because of the intrinsic complexity of biological systems. A combination of experimental and computational approaches is expected to resolve this problem.
doi:10.1038/nature01254 pmid:12432404 fatcat:angnkd6ys5fqpk3a4h6pwytkxa