Drug2ways: Reasoning over causal paths in biological networks for drug discovery

PLoS Comput Biol. 2020 Dec 2;16(12):e1008464. doi: 10.1371/journal.pcbi.1008464. eCollection 2020 Dec.

Abstract

Elucidating the causal mechanisms responsible for disease can reveal potential therapeutic targets for pharmacological intervention and, accordingly, guide drug repositioning and discovery. In essence, the topology of a network can reveal the impact a drug candidate may have on a given biological state, leading the way for enhanced disease characterization and the design of advanced therapies. Network-based approaches, in particular, are highly suited for these purposes as they hold the capacity to identify the molecular mechanisms underlying disease. Here, we present drug2ways, a novel methodology that leverages multimodal causal networks for predicting drug candidates. Drug2ways implements an efficient algorithm which reasons over causal paths in large-scale biological networks to propose drug candidates for a given disease. We validate our approach using clinical trial information and demonstrate how drug2ways can be used for multiple applications to identify: i) single-target drug candidates, ii) candidates with polypharmacological properties that can optimize multiple targets, and iii) candidates for combination therapy. Finally, we make drug2ways available to the scientific community as a Python package that enables conducting these applications on multiple standard network formats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Computer Simulation
  • Drug Discovery / methods*
  • Drug Repositioning / methods*
  • Drug Therapy
  • Humans
  • Models, Biological*
  • Neoplasms / drug therapy
  • Phenotype
  • Polypharmacology

Grants and funding

This work was developed in the Fraunhofer Cluster of Excellence "Cognitive Internet Technologies"(SM and DDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.