Lee, En-Shiun AnnieEn-Shiun AnnieLeeSze-To, Ho-Yin AntonioHo-Yin AntonioSze-ToWong, Man-HonMan-HonWongProf. LEUNG Kwong SakLau, Terrence Chi-KongTerrence Chi-KongLauWong, Andrew K. C.Andrew K. C.Wong2023-03-022023-03-022015IEEE/ACM Transactions on Computational Biology and Bioinformatics, 2015, vol. 14(2), pp. 254-2631545-59631557-9964http://hdl.handle.net/20.500.11861/7449Understanding binding cores is of fundamental importance in deciphering Protein-DNA (TF-TFBS) binding and gene regulation. Limited by expensive experiments, it is promising to discover them with variations directly from sequence data. Although existing computational methods have produced satisfactory results, they are one-to-one mappings with no site-specific information on residue/nucleotide variations, where these variations in binding cores may impact binding specificity. This study presents a new representation for modeling binding cores by incorporating variations and an algorithm to discover them from only sequence data. Our algorithm takes protein and DNA sequences from TRANSFAC (a Protein-DNA Binding Database) as input; discovers from both sets of sequences conserved regions in Aligned Pattern Clusters (APCs); associates them as Protein-DNA Co-Occurring APCs; ranks the Protein-DNA Co-Occurring APCs according to their co-occurrence, and among the top ones, finds three-dimensional structures to support each binding core candidate. If successful, candidates are verified as binding cores. Otherwise, homology modeling is applied to their close matches in PDB to attain new chemically feasible binding cores. Our algorithm obtains binding cores with higher precision and much faster runtime ( ≥ 1,600x) than that of its contemporaries, discovering candidates that do not co-occur as one-to-one associated patterns in the raw data. Availability: http://www.pami.uwaterloo.ca/~ealee/files/tcbbPnDna2015/Release.zip .enDNA-Binding ProteinCore BindingAlignment PatternsDNA SequencingSequencing DataProtein SequencesThree-Dimensional StructureProtein Data BankHomology ModelingTRANSFACSite-Specific InformationExpensive ExperimentsPairing3D StructureDNA-Binding DomainEfficient AlgorithmProtein DNATranscription Factor Binding SitesProtein PatternsDNA VariantsSequences Of Transcription FactorsMotif DiscoveryBiological DatabasesUnique ScoreSupplementary DiscussionPerformance VerificationGlobal AlignmentSequences of Transcription FactorsPeer Reviewed Journal Article10.1109/TCBB.2015.2474376