Progress and challenges in bioinformatics approaches for enhancer identification

Enhancers are cis-acting DNA elements that play critical roles in distal regulation of gene expression. Identifying enhancers is an important step for understanding distinct gene expression programs that may reflect normal and pathogenic cellular conditions. Experimental identification of enhancers...

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Bibliographic Details
Published in:Briefings in bioinformatics Vol. 17; no. 6; pp. 967 - 979
Main Authors: Kleftogiannis, Dimitrios, Kalnis, Panos, Bajic, Vladimir B.
Format: Journal Article
Language:English
Published: England Oxford University Press 01.11.2016
Subjects:
Computational Biology
Enhancer Elements, Genetic
Histones
chromatin signatures
computer science
enhancers
gene regulation
genome annotation
bioinformatics
histone modification marks
machine learning
ISSN:1467-5463, 1477-4054, 1477-4054
Online Access:Get full text
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Summary:Enhancers are cis-acting DNA elements that play critical roles in distal regulation of gene expression. Identifying enhancers is an important step for understanding distinct gene expression programs that may reflect normal and pathogenic cellular conditions. Experimental identification of enhancers is constrained by the set of conditions used in the experiment. This requires multiple experiments to identify enhancers, as they can be active under specific cellular conditions but not in different cell types/tissues or cellular states. This has opened prospects for computational prediction methods that can be used for high-throughput identification of putative enhancers to complement experimental approaches. Potential functions and properties of predicted enhancers have been catalogued and summarized in several enhancer-oriented databases. Because the current methods for the computational prediction of enhancers produce significantly different enhancer predictions, it will be beneficial for the research community to have an overview of the strategies and solutions developed in this field. In this review, we focus on the identification and analysis of enhancers by bioinformatics approaches. First, we describe a general framework for computational identification of enhancers, present relevant data types and discuss possible computational solutions. Next, we cover over 30 existing computational enhancer identification methods that were developed since 2000. Our review highlights advantages, limitations and potentials, while suggesting pragmatic guidelines for development of more efficient computational enhancer prediction methods. Finally, we discuss challenges and open problems of this topic, which require further consideration.
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ISSN:1467-5463
1477-4054
1477-4054
DOI:10.1093/bib/bbv101