College Park, MD (July 20, 2010) -- Eighty years ago, the medical establishment believed cancer was caused by a dysfunction of metabolism, but the idea went out of vogue. Now, scientists are again looking at metabolism and its role in cancer and other common diseases. Metabolism is a highly connected network of reactions that are arranged in parallel and interacting pathways. Such parallelism can mask how genes are linked with disease traits and make it difficult to treat conditions.
In a paper in the journal CHAOS, which is published by the American Institute of Physics, researchers at Harvard Medical School and Boston University analyzed ways to "break" the multiple parallel pathways of a metabolic network. The team applied a novel network algorithm to a published genome-scale model of human metabolism to design minimal "knockouts" for a wide variety of metabolic functions, such as phospholipid biosynthesis and the role of fumarase in suppressing human cancer.
The research suggests that the many pathways in the human metabolic network buffer each other to a striking degree, inducing "deep" epistasis -- the suppression of a mutation by one or more seemingly unrelated genes. Their results identify specific in vivo perturbation experiments that could confirm this deep parallelism in human metabolic pathways. "The results of our analysis could also be used to statistically probe complex relationships between genetic variation and disease," says co-author Marcin Imielinski.
The article "Deep epistasis in human metabolism" by Marcin Imielinski and Calin Belta was published in the journal CHAOS on June 30, 2010. See: http://chaos.
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Chaos is an interdisciplinary journal of non-linear science. The journal is published quarterly by the American Institute of Physics and is devoted to increasing the understanding of nonlinear phenomena and describing the manifestations in a manner comprehensible to researchers from a broad spectrum of disciplines. Special focus issues are published periodically each year and cover topics as diverse as the complex behavior of the human heart to chaotic fluid flow problems. See: http://chaos.
The American Institute of Physics is a federation of 10 physical science societies representing more than 135,000 scientists, engineers, and educators and is one of the world's largest publishers of scientific information in the physical sciences. Offering partnership solutions for scientific societies and for similar organizations in science and engineering, AIP is a leader in the field of electronic publishing of scholarly journals. AIP publishes 12 journals (some of which are the most highly cited in their respective fields), two magazines, including its flagship publication Physics Today; and the AIP Conference Proceedings series. Its online publishing platform Scitation hosts nearly two million articles from more than 185 scholarly journals and other publications of 28 learned society publishers.