title: QGRS-Conserve: a computational method for discovering evolutionarily conserved G-quadruplex motifs.
abstract: BACKGROUND
  Nucleic acids containing guanine tracts can form quadruplex structures via non-Watson-Crick base pairing. Formation of G-quadruplexes is associated with the regulation of important biological functions such as transcription, genetic instability, DNA repair, DNA replication, epigenetic mechanisms, regulation of translation, and alternative splicing. G-quadruplexes play important roles in human diseases and are being considered as targets for a variety of therapies. Identification of functional G-quadruplexes and the study of their overall distribution in genomes and transcriptomes is an important pursuit. Traditional computational methods map sequence motifs capable of forming G-quadruplexes but have difficulty in distinguishing motifs that occur by chance from ones which fold into G-quadruplexes.
  
  
  RESULTS
  We present Quadruplex forming 'G'-rich sequences (QGRS)-Conserve, a computational method for calculating motif conservation across exomes and supports filtering to provide researchers with more precise methods of studying G-quadruplex distribution patterns. Our method quantitatively evaluates conservation between quadruplexes found in homologous nucleotide sequences based on several motif structural characteristics. QGRS-Conserve also efficiently manages overlapping G-quadruplex sequences such that the resulting datasets can be analyzed effectively.
  
  
  CONCLUSIONS
  We have applied QGRS-Conserve to identify a large number of G-quadruplex motifs in the human exome conserved across several mammalian and non-mammalian species. We have successfully identified multiple homologs of many previously published G-quadruplexes that play post-transcriptional regulatory roles in human genes. Preliminary large-scale analysis identified many homologous G-quadruplexes in the 5'- and 3'-untranslated regions of mammalian species. An expectedly smaller set of G-quadruplex motifs was found to be conserved across larger phylogenetic distances. QGRS-Conserve provides means to build datasets that can be filtered and categorized in a variety of biological dimensions for more targeted studies in order to better understand the roles that G-quadruplexes play.
authors.affiliation: Department of Computer Science, Ramapo College of New Jersey, 505 Ramapo Valley Road, Mahwah, NJ 08807, USA. sfrees@ramapo.edu.
authors.forename: Scott
authors.initials: S
authors.lastname: Frees
authors.forename: Camille
authors.initials: C
authors.lastname: Menendez
authors.forename: Matt
authors.initials: M
authors.lastname: Crum
authors.forename: Paramjeet S
authors.initials: PS
authors.lastname: Bagga
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D054856:G-Quadruplexes; D006801:Humans; D059372:Nucleotide Motifs / Q000235:genetics*; D010802:Phylogeny; D017422:Sequence Analysis, DNA