TY - JOUR
T1 - Visualization of drug target interactions in the contexts of pathways and networks with reactomefiviz
AU - Blucher, Aurora S.
AU - McWeeney, Shannon K.
AU - Stein, Lincoln
AU - Wu, Guanming
N1 - Funding Information:
This project was supported by NIH grants 2U41HG003751 (L.S., G.W.), T15LM007088 (A.S.B.), 1R01CA192405 (S.K.M), and 5UL1TR000128 (S.K.M., G.W.).
Publisher Copyright:
© 2019 Blucher AS et al.
PY - 2019
Y1 - 2019
N2 - The precision medicine paradigm is centered on therapies targeted to particular molecular entities that will elicit an anticipated and controlled therapeutic response. However, genetic alterations in the drug targets themselves or in genes whose products interact with the targets can affect how well a drug actually works for an individual patient. To better understand the effects of targeted therapies in patients, we need software tools capable of simultaneously visualizing patient-specific variations and drug targets in their biological context. This context can be provided using pathways, which are process-oriented representations of biological reactions, or biological networks, which represent pathway-spanning interactions among genes, proteins, and other biological entities. To address this need, we have recently enhanced the Reactome Cytoscape app, ReactomeFIViz, to assist researchers in visualizing and modeling drug and target interactions. ReactomeFIViz integrates drug-target interaction information with high quality manually curated pathways and a genome-wide human functional interaction network. Both the pathways and the functional interaction network are provided by Reactome, the most comprehensive open source biological pathway knowledgebase. We describe several examples demonstrating the application of these new features to the visualization of drugs in the contexts of pathways and networks. Complementing previous features in ReactomeFIViz, these new features enable researchers to ask focused questions about targeted therapies, such as drug sensitivity for patients with different mutation profiles, using a pathway or network perspective.
AB - The precision medicine paradigm is centered on therapies targeted to particular molecular entities that will elicit an anticipated and controlled therapeutic response. However, genetic alterations in the drug targets themselves or in genes whose products interact with the targets can affect how well a drug actually works for an individual patient. To better understand the effects of targeted therapies in patients, we need software tools capable of simultaneously visualizing patient-specific variations and drug targets in their biological context. This context can be provided using pathways, which are process-oriented representations of biological reactions, or biological networks, which represent pathway-spanning interactions among genes, proteins, and other biological entities. To address this need, we have recently enhanced the Reactome Cytoscape app, ReactomeFIViz, to assist researchers in visualizing and modeling drug and target interactions. ReactomeFIViz integrates drug-target interaction information with high quality manually curated pathways and a genome-wide human functional interaction network. Both the pathways and the functional interaction network are provided by Reactome, the most comprehensive open source biological pathway knowledgebase. We describe several examples demonstrating the application of these new features to the visualization of drugs in the contexts of pathways and networks. Complementing previous features in ReactomeFIViz, these new features enable researchers to ask focused questions about targeted therapies, such as drug sensitivity for patients with different mutation profiles, using a pathway or network perspective.
KW - Biological pathway
KW - Boolean network
KW - Constrained fuzzy logic modeling
KW - Drug interaction visualization
KW - Functional interaction network
KW - Reactome
KW - Systems pharmacology
KW - Targeted therapy
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U2 - 10.12688/f1000research.19592.1
DO - 10.12688/f1000research.19592.1
M3 - Review article
C2 - 31372215
AN - SCOPUS:85070576363
SN - 2046-1402
VL - 8
JO - F1000Research
JF - F1000Research
M1 - 908
ER -