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Visualization of drug target interactions in the contexts of pathways and networks with ReactomeFIViz

Aurora S Blucher¹, Shannon K McWeeney^1,2, Lincoln Stein^3,4

¹Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

|August 3, 2019

Abstract:

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.

Insights

Precision medicine uses targeted therapies, but patient genetics can alter drug effectiveness. ReactomeFIViz software visualizes drug-target interactions within biological pathways and networks to understand these effects.

Area of Science:

Computational Biology
Bioinformatics
Genomics

Background:

Precision medicine relies on targeted therapies based on molecular profiles.
Genetic variations in patients can impact the efficacy of targeted drugs.
Visualizing patient-specific variations alongside drug targets in biological context is crucial.

Purpose of the Study:

To enhance software tools for visualizing and modeling drug-target interactions in biological context.
To integrate patient-specific genetic variations with drug targets using pathways and networks.
To enable researchers to investigate the impact of genetic alterations on targeted therapy response.

Main Methods:

Enhanced the Reactome Cytoscape app, ReactomeFIViz, for visualizing drug and target interactions.
Integrated drug-target interaction data with Reactome's curated pathways and human functional interaction network.
Demonstrated new features through examples of visualizing drugs within pathway and network contexts.

Main Results:

ReactomeFIViz now facilitates visualization of drug-target interactions within comprehensive biological pathways and networks.
The enhanced tool integrates manually curated pathways and a genome-wide functional interaction network from Reactome.
New features allow for the examination of drug sensitivity in relation to patient mutation profiles.

Conclusions:

The enhanced ReactomeFIViz aids researchers in understanding targeted therapy effects in the context of biological pathways and networks.
This tool supports focused investigations into how patient-specific genetic variations influence drug response.
Facilitates a pathway or network perspective for analyzing drug sensitivity and personalized medicine strategies.

Read full analysis

Keywords:

Boolean network Reactome biological pathway constrained fuzzy logic modeling drug interaction visualization functional interaction network systems pharmacology targeted therapy

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