QPARSE: searching for long-looped or multimeric G-quadruplexes potentially distinctive and druggable

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• G-quadruplexes (G4s) are non-canonical nucleic acid structures found in DNA and RNA.
• Emerging evidence highlights G4s as crucial regulators in biological processes.
• Recent discoveries include adjacent interacting G4s and G4s with stable long loops (LLPQS).

Purpose of the Study:

• To address the lack of specialized tools for identifying higher-order G-quadruplex architectures.
• To develop and present QPARSE, a novel computational tool for G4 identification.
• To analyze the genomic distribution and significance of specific G4 types.

Main Methods:

• Development of QPARSE, a tool for exhaustive searching of potential quadruplex-forming sequences (PQSs).
• QPARSE identifies degenerate PQSs with bulges/mismatches, multimeric PQSs (MPQS), and LLPQS.
• Performance assessment against known datasets and application to human gene promoters and specific case studies.

Main Results:

• QPARSE demonstrates state-of-the-art performance in identifying known G4s.
• QPARSE excels in detecting MPQS and LLPQS, which are challenging for existing algorithms.
• Comprehensive analysis of MPQS in human gene promoters and LLPQS in HIV-1, BCL2, and hTERT.

Conclusions:

• QPARSE is an effective and specialized tool for identifying diverse G-quadruplex structures.
• The tool facilitates deeper investigation into the biological roles of higher-order G4s.
• QPARSE is freely available for genomic research.