Bechtel, William
(2019)
From Parts to Mechanisms: Research Heuristics for Addressing Heterogeneity in Cancer Genetics.
[Preprint]
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Research Heuristics for Addressing Heterogeneity.final.clean.forarchive.pdf
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Abstract
A major approach to cancer research in the late 20th century was to search for genes that, when altered, initiated the development of a cell into a cancerous state (oncogenes) or failed to stop this development (tumor suppressor genes). But as researchers acquired the capacity to sequence tumors and incorporated the resulting data into databases, it became apparent that for many tumors no genes were frequently altered and that the genes altered in different tumors in the same tissue type were often distinct. To address this heterogeneity problem, many researchers looked to a higher level of organization—to mechanisms in which gene products (proteins) participated. They proposed to reduce heterogeneity by recognizing that multiple gene alterations affect the same mechanism and that it is the altered mechanism that is responsible for the cell developing one or more hallmarks of cancer. I examine how mechanisms figure in this research and focus on two heuristics researchers use to integrate proteins into mechanisms, one focusing on pathways and one focusing on clusters in networks.
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