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Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes
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CoSREM: a graph mining algorithm for the discovery of combinatorial splicing regulatory elements.

Eman Badr1, Lenwood S Heath2

  • 1Department of Computer Science, Virginia Tech, Blacksburg, Virginia, USA.

BMC Bioinformatics
|September 5, 2015
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Summary
This summary is machine-generated.

A new algorithm, Combinatorial SRE Miner (CoSREM), identifies sets of splicing regulatory elements (SREs) that control gene expression. This method advances understanding of alternative splicing in diseases and tissue specificity.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Molecular Biology

Background:

  • Alternative splicing (AS) regulates gene expression post-transcriptionally.
  • Splicing factor binding to splicing regulatory elements (SREs) dictates splicing decisions.
  • Current methods often limit SRE discovery to pairs and fixed lengths.

Purpose of the Study:

  • To develop a novel graph mining algorithm, CoSREM, for discovering combinatorial SREs in human exons.
  • To identify sets of SREs without predefined length constraints.
  • To incorporate experimental evidence for increased accuracy in SRE identification.

Main Methods:

  • Developed CoSREM, a graph mining algorithm for combinatorial SRE discovery.
  • Applied CoSREM to human exons, considering variable SRE lengths.
  • Integrated experimental evidence to enhance SRE identification accuracy.

Main Results:

  • Identified 37 SRE sets comprising both enhancer and silencer elements.
  • Validated findings against previous experimental results.
  • Discovered specific SRE sets (GGGAGG, GAGGAC) potentially involved in tumor-specific exon skipping.
  • Applied CoSREM to RNA-Seq data across multiple tissues to identify tissue-specific combinatorial SREs.

Conclusions:

  • CoSREM effectively identifies diverse combinations of splicing enhancers and silencers.
  • The algorithm is not limited by SRE size or the number of SREs in a set.
  • This approach offers new avenues for studying SREs and the role of AS in disease and tissue specificity.