title: Protein homology reveals new targets for bioactive small molecules.
abstract: BACKGROUND
  The functional impact of small molecules is increasingly being assessed in different eukaryotic species through large-scale phenotypic screening initiatives. Identifying the targets of these molecules is crucial to mechanistically understand their function and uncover new therapeutically relevant modes of action. However, despite extensive work carried out in model organisms and human, it is still unclear to what extent one can use information obtained in one species to make predictions in other species.
  
  
  RESULTS
  Here, for the first time, we explore and validate at a large scale the use of protein homology relationships to predict the targets of small molecules across different species. Our results show that exploiting target homology can significantly improve the predictions, especially for molecules experimentally tested in other species. Interestingly, when considering separately orthology and paralogy relationships, we observe that mapping small molecule interactions among orthologs improves prediction accuracy, while including paralogs does not improve and even sometimes worsens the prediction accuracy. Overall, our results provide a novel approach to integrate chemical screening results across multiple species and highlight the promises and remaining challenges of using protein homology for small molecule target identification.
  
  
  METHODS
  Homology-based predictions can be tested on our website http://www.swisstargetprediction.ch.
  
  
  BACKGROUND
  david.gfeller@unil.ch or vincent.zoete@isb-sib.ch.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Fundamental Oncology, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland and Swiss Institute of Bioinformatics (SIB), Quartier Sorge, Bâtiment Génopode, 1015 Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Gfeller
authors.affiliation: Swiss Institute of Bioinformatics (SIB), Quartier Sorge, Bâtiment Génopode, 1015 Lausanne, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zoete
mesh_terms: D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D030562:Databases, Protein; D006801:Humans; D011506:Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries