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New tools to analyze overlapping coding regions.

Amir H Bayegan1, Juan Antonio Garcia-Martin1, Peter Clote2

  • 1Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill MA, 02467, USA.

BMC Bioinformatics
|December 15, 2016
PubMed
Summary
This summary is machine-generated.

This study introduces RNAsampleCDS, a computational tool for analyzing RNA sequences with overlapping coding regions. It helps understand viral RNA evolution, particularly for HIV-1 frameshift stimulating signals.

Keywords:
Frameshift stimulating signalHCVHIV-1Overlapping coding regionRibosomal frameshift

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Molecular Evolution

Background:

  • Retroviruses use programmed ribosomal frameshifting to produce Gag and Gag-Pol polyproteins.
  • This frameshifting relies on a frameshift stimulating signal (FSS), comprising a slippery sequence and a downstream stem-loop structure.
  • The evolution of this genomic region is constrained by coding requirements, sequence, and secondary structure stability.

Purpose of the Study:

  • To develop a computational tool, RNAsampleCDS, for analyzing RNA sequences with overlapping coding regions.
  • To quantify the contribution of overlapping coding requirements to the formation of the frameshift stimulating signal in viruses like HIV-1.
  • To generalize the codon preference index (CPI) for overlapping reading frames.

Main Methods:

  • RNAsampleCDS computes the number of RNA sequences coding for specified peptides in overlapping frames.
  • The software allows simultaneous analysis of all 6 reading frames, with options for IUPAC constraints and GC-content.
  • It can calculate position-specific scoring matrices, codon usage bias, and sample valid RNA sequences.

Main Results:

  • RNAsampleCDS quantifies the role of overlapping coding in forming viral secondary structures (e.g., HIV-1 FSS).
  • The tool confirms critical nucleotide positions in HCV mutations, aligning with RNAiFold predictions.
  • Generalized CPI computation for overlapping regions, including HIV-1 Gag-Pol.

Conclusions:

  • RNAsampleCDS is a unique computational tool for evolutionary biologists studying RNA sequences.
  • The software aids in understanding complex molecular evolution constraints in viral genomes.
  • Available source code and data facilitate further research in the field.