Title
Assessing Computational Methods Of Cis-Regulatory Module Prediction
Abstract
Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. Without a comprehensive comparison of their performance, the reliability and accuracy of these tools remains unclear. Faced with a large number of different tools that address this problem, we summarized and categorized them based on search strategy and input data requirements. Twelve representative methods were chosen and applied to predict CRMs from the Drosophila CRM database REDfly, and across the human ENCODE regions. Our results show that the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. We analyze the principal features that distinguish the methods that performed well, identify weaknesses leading to poor performance, and provide a guide for users. We also propose key considerations for the development and evaluation of future CRM-prediction methods.
Year
DOI
Venue
2010
10.1371/journal.pcbi.1001020
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
transcription factor binding site,roc curve,area under curve,algorithms,cis regulatory module,phylogeny,binding site,transcription factors,evolutionary conservation,computational biology,cluster analysis
Genome,ENCODE,REDfly,DNA binding site,Predictive power,Biology,Genome human,Bioinformatics,Genetics,Cis-regulatory module
Journal
Volume
Issue
ISSN
6
12
1553-734X
Citations 
PageRank 
References 
15
0.81
23
Authors
3
Name
Order
Citations
PageRank
Jing Su1276.98
Sarah A Teichmann223922.64
T Down350156.90