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Artificial Intelligence helps predict cancer
Uncle Joe smokes a pack a day, drinks like a fish and lives into his late 80's. His brother, with a similar lifestyle, dies of cancer at 55. Why do some people develop disease or disorders while others do not? New research fromTufts University and the University of Florida, could help provide some answers. Scientists used an artificial intelligence approach to identify aberrant cells.
Published in Science Signaling, their findings reflect the first time artificial intelligence has explained why some groups of cells deviate from normal during embryogenesis. According to senior author Michael Levin PhD, the Vannevar Bush Professor of Biology at Tufts and director of the Tufts Center for Regenerative and Developmental Biology.
The paper builds on the center's earlier studies applying artificial intelligence to help explain how the flat worm, planaria, regenerates.
In the work, researchers applied artificial intelligence called "evolutionary computation" to pinpoint molecular mechanisms which induce normal pigment cells in African clawed frog (Xenopus laevis) embryos to metastasize. A series of drugs were used to disrupt embryonic cells' normal bioelectrical and serotonin signaling at a crucial stage of development. Serotonin is primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system (CNS) of animals, including humans.
Depending on which protein in the bioelectric pathway was tweaked, only a certain percentage of the frogs developed melanoma, while the rest remained healthy. "There's randomness to this process. It doesn't have the same result in all animals exposed to precisely the same agent, which mimics the variability in human responses to cancer-inducing stimuli," added Levin.
Furthermore, the tadpoles that did develop melanoma developed it in every pigment cell — each frog was either 100 percent metastatic or completely normal. Essentially all pigment cells in a tadpole are part of a single coin, which either flips heads (normal) or tails (cancerous) — said Levin.
Maria Lobikin PhD, a recent doctoral graduate from the Levin laboratory and first author on the paper, first identified all the building blocks: receptors, hormones and other signaling proteins, in the serotonin signaling pathway regulating the melanoma-like cell response. Then, the team applied artificial intelligence to mimic evolution and generate a signaling network for a "virtual embryo" which exhibited the same behavior observed in tadpoles.
Like biological evolution, evolutionary computation uses incremental improvement and selection to rapidly reach a conclusion to a hypothesis. Traditional lab experiments must randomly and exhaustively test each possible outcome suggested by experimentation, then retest to confirm.
The knowledge from these molecular pathways has implications not only for new treatments and targets for tumor prevention, but for understanding many other seemingly random changes found in cells of living organisms.
Abstract: Driving melanocyte proliferation and invasion
In addition to Levin and Lobikin, paper authors were Douglas J. Blackiston and Elizabeth Tkachenko of the Department of Biology and Center for Regenerative and Developmental Biology, Tufts University; Daniel Lobo, formerly of the Levin laboratory and now at the University of Maryland in Baltimore; and Christopher J. Martyniuk of the Center for Environmental and Human Toxicology and Department of Physiological Sciences, UF Genetics Institute, University of Florida.
M. Lobikin, D. Lobo, D.J. Blackiston, C.J. Martyniuk, E. Tkachenko, M. Levin, "Serotonergic regulation of melanocyte conversion: a bioelectrically regulated network for stochastic all-or-none hyperpigmentation". Sci. Signal.8, ra99 (2015).
Tufts University, located on three Massachusetts campuses in Boston, Medford/Somerville and Grafton, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoy a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.
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