Fast approximate shortest hyperpaths for inferring pathways in cell signaling hypergraphs

Spencer Krieger, John Kececioglu

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

Abstract

Cell signaling pathways, which are a series of reactions that start at receptors and end at transcription factors, are basic to systems biology. Properly modeling the reactions in such pathways requires directed hypergraphs, where an edge is now directed between two sets of vertices. Inferring a pathway by the most parsimonious series of reactions then corresponds to finding a shortest hyperpath in a directed hypergraph, which is NP-complete. The state of the art for shortest hyperpaths in cell-signaling hypergraphs solves a mixed-integer linear program to find an optimal hyperpath that is restricted to be acyclic, and offers no efficiency guarantees. We present for the first time a heuristic for general shortest hyperpaths that properly handles cycles, and is guaranteed to be efficient. Its accuracy is demonstrated through exhaustive experiments on all instances from the standard NCI-PID and Reactome pathway databases, which show the heuristic finds a hyperpath that matches the state-of-the-art mixed-integer linear program on over 99% of all instances that are acyclic. On instances where only cyclic hyperpaths exist, the heuristic surpasses the state-of-the-art, which finds no solution; on every such cyclic instance, enumerating all possible hyperpaths shows that the solution found by the heuristic is in fact optimal.

Original languageEnglish (US)
Title of host publication21st International Workshop on Algorithms in Bioinformatics, WABI 2021
EditorsAlessandra Carbone, Mohammed El-Kebir
PublisherSchloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing
ISBN (Electronic)9783959772006
DOIs
StatePublished - Jul 1 2021
Event21st International Workshop on Algorithms in Bioinformatics, WABI 2021 - Virtual, Chicago, United States
Duration: Aug 2 2021Aug 4 2021

Publication series

NameLeibniz International Proceedings in Informatics, LIPIcs
Volume201
ISSN (Print)1868-8969

Conference

Conference21st International Workshop on Algorithms in Bioinformatics, WABI 2021
Country/TerritoryUnited States
CityVirtual, Chicago
Period8/2/218/4/21

Keywords

  • Cell signaling networks
  • Directed hypergraphs
  • Efficient heuristics
  • Hyperpath enumeration
  • Reaction pathways
  • Shortest hyperpaths
  • Systems biology

ASJC Scopus subject areas

  • Software

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