Discovering protein-DNA binding sequence patterns using association rule mining.
Protein-DNA bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) play an essential role in transcriptional regulation. Over the past decades, significant efforts have been made to study the principles for protein-DNA bindings. However, it is considered that there are no simple one-to-one rules between amino acids and nucleotides. Many methods impose complicated features beyond sequence patterns. Protein-DNA bindings are formed from associated amino acid and nucleotide sequence pairs, which determine many functional characteristics. Therefore, it is desirable to investigate associated sequence patterns between TFs and TFBSs. With increasing computational power, availability of massive experimental databases on DNA and proteins, and mature data mining techniques, we propose a framework to discover associated TF-TFBS binding sequence patterns in the most explicit and interpretable form from TRANSFAC. The framework is based on association rule mining with Apriori algorithm. The patterns found are evaluated by quantitative measurements at several levels on TRANSFAC. With further independent verifications from literatures, Protein Data Bank and homology modeling, there are strong evidences that the patterns discovered reveal real TF-TFBS bindings across different TFs and TFBSs, which can drive for further knowledge to better understand TF-TFBS bindings.
Leung
Kwong-Sak
KS
Department of Computer Science & Engineering, The Chinese University of Hong Kong, and Hong Kong Bioinformatics Centre, Shatin, NT, Hong Kong, China.
Wong
Ka-Chun
KC
Chan
Tak-Ming
TM
Wong
Man-Hon
MH
Lee
Kin-Hong
KH
Lau
Chi-Kong
CK
Tsui
Stephen K W
SK
D000465:Algorithms; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D057225:Data Mining / Q000379:methods*; D030541:Databases, Genetic; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D040681:Structural Homology, Protein; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA