Connectivity Mapping: Methods and Applications

Alexandra B. Keenan, Megan L. Wojciechowicz, Zichen Wang, Kathleen M. Jagodnik, Sherry L. Jenkins, Alexander Lachmann, Avi Ma'ayan

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations

Abstract

Connectivity mapping resources consist of signatures representing changes in cellular state following systematic small-molecule, disease, gene, or other form of perturbations. Such resources enable the characterization of signatures from novel perturbations based on similarity; provide a global view of the space of many themed perturbations; and allow the ability to predict cellular, tissue, and organismal phenotypes for perturbagens. A signature search engine enables hypothesis generation by finding connections between query signatures and the database of signatures. This framework has been used to identify connections between small molecules and their targets, to discover cell-specific responses to perturbations and ways to reverse disease expression states with small molecules, and to predict small-molecule mimickers for existing drugs. This review provides a historical perspective and the current state of connectivity mapping resources with a focus on both methodology and community implementations.

Original languageEnglish
Pages (from-to)69-92
Number of pages24
JournalAnnual review of biomedical data science
Volume2
DOIs
StatePublished - 20 Jul 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Annual Review of Biomedical Data Science.

Keywords

  • drug repositioning
  • network analysis
  • responsome
  • signature commons
  • systems biology
  • systems pharmacology

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