Probabilistic and Dynamic Molecule-Disease Interaction Modeling for Drug Discovery

Tianfan Fu, Cao Xiao, Cheng Qian, Lucas M. Glass, Jimeng Sun

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Drug discovery aims at finding promising drug molecules for treating target diseases. Existing computational drug discovery methods mainly depend on molecule databases, ignoring valuable data collected from clinical trials. In this work, we propose PRIME to leverage high-quality drug molecules and drug-disease relations in historical clinical trials to narrow down the molecular search space in drug discovery. PRIME also introduces time dependency constraints to model evolving drug-disease relations using a probabilistic deep learning model that can quantify model uncertainty. We evaluated PRIME against leading models on both de novo design and drug repurposing tasks. Results show that compared with the best baselines, PRIME achieves 25.9% relative improvement (i.e., reduction) in average hit-ranking on drug repurposing and 47.6% relative improvement in success rate on de novo design.

Original languageEnglish (US)
Title of host publicationKDD 2021 - Proceedings of the 27th ACM SIGKDD Conference on Knowledge Discovery and Data Mining
PublisherAssociation for Computing Machinery
Pages404-414
Number of pages11
ISBN (Electronic)9781450383325
DOIs
StatePublished - Aug 14 2021
Event27th ACM SIGKDD Conference on Knowledge Discovery and Data Mining, KDD 2021 - Virtual, Online, Singapore
Duration: Aug 14 2021Aug 18 2021

Publication series

NameProceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining

Conference

Conference27th ACM SIGKDD Conference on Knowledge Discovery and Data Mining, KDD 2021
Country/TerritorySingapore
CityVirtual, Online
Period8/14/218/18/21

Keywords

  • drug discovery
  • probabilistic deep learning

ASJC Scopus subject areas

  • Software
  • Information Systems

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