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A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
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Sigma-2: Multiple sequence alignment of non-coding DNA via an evolutionary model.

Gayathri Jayaraman1, Rahul Siddharthan

  • 1The Institute of Mathematical Sciences, Taramani, Chennai 600 113, India. rsidd@imsc.res.in.

BMC Bioinformatics
|September 18, 2010
PubMed
Summary
This summary is machine-generated.

Sigma-2 improves non-coding DNA alignment by using an evolutionary model to detect homology, outperforming other programs in specificity and sensitivity. This advancement is crucial for regulatory genomics and whole-genome alignment.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Most multiple sequence alignment programs assume homology and penalize insertions/deletions, which is unsuitable for less conserved non-coding DNA.
  • Previous Sigma version 1 successfully eliminated spurious alignments but had low sensitivity on synthetic data.
  • Sigma 1 used p-values and optional background models for alignment significance, but lacked a sophisticated evolutionary model.

Purpose of the Study:

  • To develop an improved multiple sequence alignment program (Sigma-2) for non-coding DNA.
  • To incorporate a sophisticated evolutionary model for more sensitive detection of homology.
  • To enhance the assessment of alignment significance using likelihood-based methods.

Main Methods:

  • Incorporated an evolutionary model into the Sigma program for non-coding DNA alignment.
  • Calculated p-values using a sophisticated evolutionary model that accounts for mutation and fixation.
  • Implemented a transition matrix for varying nucleotide substitution rates and allowed for differing functional constraints.

Main Results:

  • Sigma-2 significantly outperforms other programs in specificity, minimizing alignment of spuriously similar regions.
  • Sigma-2 achieves sensitivity comparable to the best current alignment programs.
  • Demonstrated improved performance on both real and synthetic datasets.

Conclusions:

  • Conservation rates in intergenic DNA may be overestimated by current methods.
  • Accurate alignment of non-coding DNA is critical for regulatory genomics and whole-genome alignment.
  • Sigma-2 represents a significant advancement in aligning non-coding DNA accurately.