G4-iM Grinder: DNA and RNA G-Quadruplex, i-Motif and higher order structure search and analyser tool

ABSTRACT Herein, we present G4-iM Grinder as a system for potential G4, i-Motif and higher-order structure identification and characterization. Several grading tools of biological relevance and G4 in vitro formation probability are included in this highly modulable and robust engine. G4-iM Grinder improves other current quadruplex search engines when compared in capabilities and processing time. We used G4-iM Grinder in the analysis of the complete human genome whilst focusing on frequency and score of G-based structures. We studied the most recurrent potential quadruplex sequences (PQS) and the longest highest scoring potential higher order quadruplex sequences (PHOQS) in our genome. As proof of the analytical capabilities of G4-iM Grinder, we also analysed a new PHOQS and predicted the most probable PQS subunits to form it. Taking the human average PQS density as reference, we examined the genomes of organisms that cause leishmaniosis, diphtheria, brucellosis, meningitis, pneumonia, toxoplasmosis, tuberculosis, leprosy, AIDS, dengue fever and hepatitis C, and found they are very rich in PQS. G4-iM Grinder identified within many of these organisms several already known-to-form G4 sequences. Together, this suggests that G4-quadruplexes may potentially be important therapeutic targets against many of these organisms that currently kill millions worldwide. GRAPHICAL ABSTRACT