title: Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.
abstract: BACKGROUND
  An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype.
  
  
  RESULTS
  The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways.
  
  
  CONCLUSIONS
  Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.
authors.affiliation: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Sonia
authors.initials: S
authors.lastname: Liggi
authors.forename: Georgios
authors.initials: G
authors.lastname: Drakakis
authors.forename: Alexios
authors.initials: A
authors.lastname: Koutsoukas
authors.forename: Isidro
authors.initials: I
authors.lastname: Cortes-Ciriano
authors.forename: Patricia
authors.initials: P
authors.lastname: Martínez-Alonso
authors.forename: Thérèse E
authors.initials: TE
authors.lastname: Malliavin
authors.forename: Adrian
authors.initials: A
authors.lastname: Velazquez-Campoy
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Brewerton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bodkin
authors.forename: David A
authors.initials: DA
authors.lastname: Evans
authors.forename: Robert C
authors.initials: RC
authors.lastname: Glen
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Carrodeguas
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019295:Computational Biology; D003198:Computer Simulation; D051379:Mice; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D054852:Small Molecule Libraries