CBS Computational Biology Services

The innovation of experimental design is an area where computational biology can have an important impact. In spite of this, applications of computational biology in this area are not common, probably because there is a lack of the necessary cross-disciplinary expertise, i.e., a profound knowledge in both experimental and computational Biology. Such skills are missing, although this kind of mixed formation is now under way in some top-class institutions, such as, Harvard, MIT, Cornell, Rockefeller, and Memorial Sloan-Kettering Hospital, Princeton, Berkeley, and Virginia. CBS provides to its clients this cross-disciplinary know-how. CBS has a vast experience not only in computational biology but also in molecular and cellular biology (see list of publications).

An example where the experimental design was successfully changed with the help of computational biology is the exposure of cells to hydrogen peroxide (H₂O₂), the main cellular oxidant. H₂O₂ is usually given to cells as an initial dose (bolus addition). Because cells remove H₂O₂ rapidly, to observe a biological effect large doses are needed. This causes disruption of cellular homeostasis, and consequential, the results obtained are often artifactual. An alternative experimental design is the steady-sate titration in which H₂O₂ is delivered continuously, mimicking the endogenous production. In this approach one needs to measure the kinetics of H₂O₂ cellular consumption, and with this knowledge the rate of production of H₂O₂ needed to achieve a desired H₂O₂ concentration is calculated. By changing the rate of production of H₂O₂, the steady state level of H₂O₂ is also changed, and therefore cellular processes can be rigorously titrated with concentrations of H₂O₂. Not only this approach is more physiological than the bolus addition approach but it also provides the functional curves that are needed for the construction of mathematical models. This approach has been successfully applied to the titration of apoptosis and necrosis in human cells (Free Rad. Biol. Med., 30, 1008-1018 and Biochem. J., 356, 549-555).