CoSREM: a graph mining algorithm for the discovery of combinatorial splicing regulatory elements

BMC Bioinformatics
Eman Badr, Lenwood S Heath

Abstract

Alternative splicing (AS) is a post-transcriptional regulatory mechanism for gene expression regulation. Splicing decisions are affected by the combinatorial behavior of different splicing factors that bind to multiple binding sites in exons and introns. These binding sites are called splicing regulatory elements (SREs). Here we develop CoSREM (Combinatorial SRE Miner), a graph mining algorithm to discover combinatorial SREs in human exons. Our model does not assume a fixed length of SREs and incorporates experimental evidence as well to increase accuracy. CoSREM is able to identify sets of SREs and is not limited to SRE pairs as are current approaches. We identified 37 SRE sets that include both enhancer and silencer elements. We show that our results intersect with previous results, including some that are experimental. We also show that the SRE set GGGAGG and GAGGAC identified by CoSREM may play a role in exon skipping events in several tumor samples. We applied CoSREM to RNA-Seq data for multiple tissues to identify combinatorial SREs which may be responsible for exon inclusion or exclusion across tissues. The new algorithm can identify different combinations of splicing enhancers and silencers without assuming a predefined...Continue Reading

References

Jul 17, 1991·Journal of the National Cancer Institute·R J SlebosS Rodenhuis
Aug 7, 1999·Stem Cells·D S Goodsell
Sep 18, 1999·Respirology : Official Journal of the Asian Pacific Society of Respirology·M KinoshitaK Oizumi
Jul 13, 2002·Science·William G FairbrotherChristopher B Burge
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Jun 26, 2003·Nucleic Acids Research·Luca CartegniAdrian R Krainer
Nov 15, 2003·Science·Jernej UleRobert B Darnell
Dec 19, 2003·Nucleic Acids Research·Donna KarolchikW James Kent
May 18, 2004·Genes & Development·Xiang H-F Zhang, Lawrence A Chasin
Dec 21, 2004·Cell·Zefeng WangChristopher B Burge
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Arianne J MatlinChristopher W J Smith
Aug 2, 2005·Molecular and Cellular Biology·Xiang H-F ZhangLawrence A Chasin
Dec 31, 2005·Nucleic Acids Research·Stefan StammThangavel Alphonse Thanaraj
Jun 7, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Annemieke Aartsma-RusJudith C T van Deutekom
Apr 3, 2008·Advances in Experimental Medicine and Biology·Lawrence A Chasin
Sep 19, 2008·Genome Research·Brad A FriedmanChristopher B Burge
Apr 3, 2009·Nucleic Acids Research·François-Olivier DesmetChristophe Béroud
Jan 30, 2010·Nucleic Acids Research·Amir GorenGil Ast
Apr 9, 2010·Nature Reviews. Genetics·Hadas KerenGil Ast
Jun 10, 2010·Bioinformatics·Yoseph BarashBrendan J Frey
Aug 13, 2010·Nucleic Acids Research·Mikita SuyamaPeer Bork
Aug 14, 2010·Genome Biology·Shengdong Ke, Lawrence A Chasin
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Xinshu Xiao, Jae-Hyung Lee
Jun 11, 2011·Genome Research·Shengdong KeLawrence A Chasin
Sep 17, 2011·Human Mutation·Francesco PivaGiovanni Principato
Jun 2, 2012·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Jing ZhangLiang Chen
Jun 23, 2012·Genome Research·Simon AndersWolfgang Huber
Nov 3, 2012·Nucleic Acids Research·Matteo GiuliettiGraziano Pesole
Nov 21, 2012·Briefings in Functional Genomics·Emanuele BurattiFrancisco E Baralle
Dec 4, 2012·Nucleic Acids Research·Paul FlicekStephen M J Searle
Sep 26, 2013·BMB Reports·Zhiguo EJianhua Zhou
Dec 7, 2013·Interdisciplinary Sciences, Computational Life Sciences·Rami AlroobiSaeed Salem

❮ Previous
Next ❯

Citations

Mar 6, 2019·Frontiers in Genetics·Wei ChenHao Lin

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
RNA-Seq
CLIP

Software Mentioned

CoSREM
Spliceseq
GenMCS
AEdb
- F
Topology
ESEfinder
SpliceAid
ModDFS
Human Splicing Finder

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.