PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 40825076

G4SNVHunter: An R/Bioconductor Package for Evaluating SNV-Induced Disruption of G-Quadruplex Structures Leveraging the G4Hunter Algorithm.

Rongxin Zhang·Wenyong Zhu·Ke Xiao·Jean-Louis Mergny·Xiao Sun
View original source ↗Export metadata ↓

Abstract

G-quadruplexes (G4s) are nucleic acid secondary structures with important regulatory functions. Single-nucleotide variants (SNVs), one of the most common forms of genetic variation, can potentially impact the formation of G4 structures if they occur within G4 regions. However, there is currently a lack of software tools specifically designed to assess such effects. Here, we present an R/Bioconductor package named G4SNVHunter, which enables rapid detection of variants that may disrupt G4 structures. This tool, based on the core principles of the G4Hunter algorithm, can provide precise quantitative assessment of the propensity for G4 formation within genomic sequences. Specialized experimental methods can then be designed based on the results provided by G4SNVHunter to further verify the specific functions of the affected G4 structures, facilitating deeper insights into the biological impacts of genetic variants from the perspective of G4 structures. To showcase the functionality of the G4SNVHunter package, we analyzed the Neandertal and Denisovan archaic introgressed variants detected by the Sprime software, and identified approximately 5,800 variants located within G4 regions, among which around 230 may impair G4 structure formation propensity. The source code for the G4SNVHunter package has been publicly released under the MIT license at https://github.com/rongxinzh/G4SNVHunter and https://bioconductor.org/packages/devel/bioc/html/G4SNVHunter.html.

Explore related subjects

G-QuadruplexesAlgorithmsSoftwarePolymorphism, Single NucleotideHumansComputational BiologyAnimalsJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rongxin Zhang, Wenyong Zhu, Ke Xiao, Jean-Louis Mergny, Xiao Sun. 2025-08-18. G4SNVHunter: An R/Bioconductor Package for Evaluating SNV-Induced Disruption of G-Quadruplex Structures Leveraging the G4Hunter Algorithm.. https://doi.org/10.1371/journal.pcbi.1013368

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Structures and dynamics of the major G-quadruplex in the human PDGFR-β gene promoter: insights into vacancy G-quadruplex formation.

Overexpression of PDGFR-β (platelet-derived growth factor receptor beta) kinase contributes to diverse human diseases, including cancers, cardiovascular disorders, and fibrosis. G-quadruplexes (G4s) formed in the PDGFR-β promoter act as transcriptional repressors and represent attractive therapeutic targets. We previously reported that the major G4-forming region of the PDGFR-β promoter adopts a unique broken-strand G4, whereas truncation of this sequence generates a vacancy G4 (vG4) that can be filled-in by external guanine analogs or metabolites and further stabilized by small molecules, suggesting a potential regulatory mechanism and opportunity for selective drug targeting. However, the relationship between broken-strand G4s and vG4s remains unclear. Here, we demonstrate that the PDGFR-β promoter sequence forms a dynamic equilibrium between two broken-strand G4 conformations that interconvert on the millisecond timescale, with vG4 serving as an intermediate. We determined the high-resolution NMR structures of these interconverting G4s, which share a conserved vG4 core but differ in their intramolecular guanine "fill-in." Both conformations feature a stabilizing G-G capping base pair unique to the PDGFR-β promoter. These findings elucidate the structural details of broken-strand PDGFR-β promoter G4s and the mechanism of vG4 formation, providing critical insights for selective drug targeting and establishing a framework for rational design of small molecules to modulate PDGFR-β transcription.

G-Quadruplexes↗
PubMed2026

Conservation of Long G4-rich (LG4) genomic enhancer regulations.

Long G4-rich regions (LG4s) are defined as DNA sequences containing a high density of guanine triplets capable of forming non-B DNA structures called G-quadruplexes (G4s). These regions frequently overlap with enhancers, which are regulatory DNA elements that modulate gene expression by interacting with DNA regions that dictate where transcription is initiated known as promoters. While LG4s have now been well-characterized in the human genome, neither LG4 occurrence, nor the ability of LG4s to function as enhancers, in other species has been described. To address this, we screened the genomes of 16 different species from various taxa to identify LG4s and then determined if they were conserved, and additionally, we show the ability of one of the conserved LG4s to interact with its cognate promoter in vitro is functionally maintained across species. Our analyses characterized a number of previously unreported LG4s in the human genome as well as LG4s in 13 additional species. Of note, we identified a highly conserved LG4 enhancer predicted to regulate over 40 genes. This LG4 is embedded in the MAZ (Myc-Associated Zinc finger protein) locus, and we find this LG4 possesses the ability to directly interact with the same target promoter in both human and mouse. In summary, this work describes LG4s in the genomes of both unicellular and multicellular species including vertebrates, invertebrates, plants, and fungi, and finds many of these LG4 sequences highly conserved.

G-Quadruplexes↗
PubMed2026

G-quadruplex upstream of PAX9 TSS acts as a 3D-genome scaffold to remotely silence X-linked genes and modulate cell-cycle progression.

G-quadruplexes (G4s) are non-canonical DNA secondary structures that act as local replication barriers and transcriptional regulators. Whether G4 can simultaneously influence splicing, DNA replication, and long-range, trans-chromosomal gene regulation remains untested. Here we combined in vitro biophysics, CRISPR mutagenesis and multi-omics to dissect a conserved G4 motif (QS1) located ~173 bp upstream of the PAX9 transcription start site. CD spectroscopy confirmed that the wild-type, but not the G-to-T mutant sequence, folds into a stable parallel G4 under physiological K+. In human cells, disruption of the QS1 G4 changed chromatin accessibility, remotely down-regulated a cohort of X-linked genes, accelerated migration and delayed G1/S progression. Integrative analysis of ATAC-seq, RNA-seq profiling reveals that the QS1 G4 acts as a three-dimensional genome scaffold linking PAX9 to cell-cycle and metabolic networks. Our findings establish a pleiotropic role for a single promoter G4 in coordinating DNA replication stress, chromatin architecture and trans-chromosomal transcriptional control.

G-Quadruplexes↗