Title
Discovering approximate-associated sequence patterns for protein-DNA interactions.
Abstract
The bindings between transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental protein-DNA interactions in transcriptional regulation. Extensive efforts have been made to better understand the protein-DNA interactions. Recent mining on exact TF-TFBS-associated sequence patterns (rules) has shown great potentials and achieved very promising results. However, exact rules cannot handle variations in real data, resulting in limited informative rules. In this article, we generalize the exact rules to approximate ones for both TFs and TFBSs, which are essential for biological variations.A progressive approach is proposed to address the approximation to alleviate the computational requirements. Firstly, similar TFBSs are grouped from the available TF-TFBS data (TRANSFAC database). Secondly, approximate and highly conserved binding cores are discovered from TF sequences corresponding to each TFBS group. A customized algorithm is developed for the specific objective. We discover the approximate TF-TFBS rules by associating the grouped TFBS consensuses and TF cores. The rules discovered are evaluated by matching (verifying with) the actual protein-DNA binding pairs from Protein Data Bank (PDB) 3D structures. The approximate results exhibit many more verified rules and up to 300% better verification ratios than the exact ones. The customized algorithm achieves over 73% better verification ratios than traditional methods. Approximate rules (64-79%) are shown statistically significant. Detailed variation analysis and conservation verification on NCBI records demonstrate that the approximate rules reveal both the flexible and specific protein-DNA interactions accurately. The approximate TF-TFBS rules discovered show great generalized capability of exploring more informative binding rules.
Year
DOI
Venue
2011
10.1093/bioinformatics/btq682
Bioinformatics
Keywords
Field
DocType
approximate result,tfbs rule,exact rule,approximate-associated sequence pattern,approximate tf,better verification ratio,dna interaction,tf core,transcription factor,approximate rule,customized algorithm,protein dna interaction
Data mining,DNA binding site,Computer science,DNA,Bioinformatics,Protein Data Bank,TRANSFAC,Protein Data Bank (RCSB PDB)
Journal
Volume
Issue
ISSN
27
4
1367-4811
Citations 
PageRank 
References 
8
0.50
19
Authors
7
Name
Order
Citations
PageRank
Tak-ming Chan119013.57
Ka-Chun Wong229140.18
Kin-Hong Lee325726.27
Man Hon Wong4814233.13
Chi-Kong Lau580.50
Stephen K.-W. Tsui613012.70
Kwong-Sak Leung71887205.58