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Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome
Informatics and Bio-computing Platform, Ontario Institute for Cancer Research, Toronto, ON, M5G0A3, Canada
European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK
Department of Biochemistry, NYU School of Medicine, New York, NY 10016, USA
* Author to whom correspondence should be addressed.
Received: 8 October 2012; in revised form: 31 October 2012 / Accepted: 2 November 2012 / Published: 8 November 2012
Abstract: Reactome describes biological pathways as chemical reactions that closely mirror the actual physical interactions that occur in the cell. Recent extensions of our data model accommodate the annotation of cancer and other disease processes. First, we have extended our class of protein modifications to accommodate annotation of changes in amino acid sequence and the formation of fusion proteins to describe the proteins involved in disease processes. Second, we have added a disease attribute to reaction, pathway, and physical entity classes that uses disease ontology terms. To support the graphical representation of “cancer” pathways, we have adapted our Pathway Browser to display disease variants and events in a way that allows comparison with the wild type pathway, and shows connections between perturbations in cancer and other biological pathways. The curation of pathways associated with cancer, coupled with our efforts to create other disease-specific pathways, will interoperate with our existing pathway and network analysis tools. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as an example, we show how Reactome annotates and presents the altered biological behavior of EGFR variants due to their altered kinase and ligand-binding properties, and the mode of action and specificity of anti-cancer therapeutics.
Keywords: pathway database; pathway visualization; network visualization; cancer annotation; EGFR signaling
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Cite This Article
MDPI and ACS Style
Milacic, M.; Haw, R.; Rothfels, K.; Wu, G.; Croft, D.; Hermjakob, H.; D'Eustachio, P.; Stein, L. Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome. Cancers 2012, 4, 1180-1211.
Milacic M, Haw R, Rothfels K, Wu G, Croft D, Hermjakob H, D'Eustachio P, Stein L. Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome. Cancers. 2012; 4(4):1180-1211.
Milacic, Marija; Haw, Robin; Rothfels, Karen; Wu, Guanming; Croft, David; Hermjakob, Henning; D'Eustachio, Peter; Stein, Lincoln. 2012. "Annotating Cancer Variants and Anti-Cancer Therapeutics in Reactome." Cancers 4, no. 4: 1180-1211.