Abstract
MotivationThere is an increasing amount of data coming from genome-wide studies identifying disease-specific survivability-essential proteins and host factors critical to a cell becoming infected. Targeting such proteins has a strong potential for targeted, precision therapies. Typically however, too few of them are drug targetable. An alternative approach is to influence them through drug targetable proteins upstream of them. Structural target network controllability is a suitable solution to this problem. It aims to discover suitable source nodes (e.g. drug targetable proteins) in a directed interaction network that can control (through a suitable set of input functions) a desired set of targets.ResultsWe introduce NetControl4BioMed, a free open-source web-based application that allows users to generate or upload directed protein–protein interaction networks and to perform target structural network controllability analyses on them. The analyses can be customized to focus the search on drug targetable source nodes, thus providing drug therapeutic suggestions. The application integrates protein data from HGNC, Ensemble, UniProt, NCBI and InnateDB, directed interaction data from InnateDB, Omnipath and SIGNOR, cell-line data from COLT and DepMap, and drug–target data from DrugBank.Availabilityand implementationThe application and data are available online at https://netcontrol.combio.org/. The source code is available at https://github.com/Vilksar/NetControl4BioMed under an MIT license.
Highlights
Genome-wide association studies led in the last few years to an increasing availability of data on disease-specific survivability-essential genes (Koh et al, 2012) and on host factors critical to cell infection (Daniloski et al, 2021)
We introduce NetControl4BioMed, a free open-source webbased software, aimed at applications in biomedicine and allowing for: (i) constructing directed protein–protein interaction networks, (ii) structural target network controllability analysis focused on identifying effective drug-combinations and (iii) sharing networks
We present a new web application for network generation and network structural target controllability analysis, with a focus on biomedicine
Summary
Genome-wide association studies led in the last few years to an increasing availability of data on disease-specific survivability-essential genes (Koh et al, 2012) and on host factors critical to cell infection (Daniloski et al, 2021). We introduce NetControl4BioMed, a free open-source webbased software, aimed at applications in biomedicine and allowing for: (i) constructing directed protein–protein interaction networks, (ii) structural target network controllability analysis focused on identifying effective drug-combinations and (iii) sharing networks. NetControl4BioMed allows multi-user collaborative access to building directed protein–protein interaction networks around a set of seed proteins of interest, to upload such networks from external platforms, and to perform structural target controllability analyses with a focus on drug combination identification. In comparison to CytoCtrlAnalyser, NetControl4BioMed offers the ability to generate directed protein–protein interaction networks, a much more customizable search, integration with multiple external databases, including drug data and several cell line gene essentiality data, a cloud-based approach to network analysis, independent of the performance of the user’s own system, and the possibility for multi-user collaboration. The application provides a set of 1578 pre-compiled protein collections, consisting of 52 sets of disease-specific survivability-essential genes for several cancer cell-lines from COLT (Koh et al, 2012), the 1526 sets of mutated genes for several cancer cell-lines from DepMap (Boehm et al, 2021), and the 9 sets of drug–target genes from DrugBank (Wishart et al, 2018)
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