By the company they keep: interaction networks define the binding ability of transcription factors

Abstract

Access to genome-wide data provides the opportunity to address questions concerning the ability of transcription factors (TFs) to assemble in distinct macromolecular complexes. Here, we introduce the PAnDA (Protein And DNA Associations) approach to characterize DNA associations with human TFs using expression profiles, protein-protein interactions and recognition motifs. Our method predicts TF binding events with >0.80 accuracy revealing cell-specific regulatory patterns that can be exploited for future investigations. Even when the precise DNA-binding motifs of a specific TF are not available, the information derived from protein-protein networks is sufficient to perform high-confidence predictions (area under the ROC curve of 0.89). PAnDA is freely available at http://service.tartaglialab.com/new_submission/panda.The research leading to these results has received funding from the European Research Council under the European/nUnion’s Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreementRIBOMYLOME 309545; the Fundació La Marató de TV3 (20142731); and the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’ (SEV-2012-0208). Funding for Open Access charge: European Union’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement RIBOMYLOME 309545 and Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’ (SEV-2012-0208)