The authors conducted a systematic search for potential G-quadruplex-forming sequences in the human genome, focusing on the prevalence and distribution of specific sequence motifs. They used arithmetic ratio and probability techniques to identify frequent and systematic occurrences of certain sequence types, particularly those containing CCTGT in the first 'loop' position. The study highlights the importance of identifying biologically relevant quadruplex sequences, which may serve as therapeutic targets. The analysis revealed that while many sequences do not form stable quadruplexes, some, such as those containing CCTGT and CCTGTCAT, stand out due to their frequency and potential functionality. The results also showed that the distribution of loop sequences within quadruplexes can provide insights into their stability and function. The study emphasizes the need for further experimental validation to correlate the occurrence of these sequences with biological functions, such as RNA expression levels and protein interactions.The authors conducted a systematic search for potential G-quadruplex-forming sequences in the human genome, focusing on the prevalence and distribution of specific sequence motifs. They used arithmetic ratio and probability techniques to identify frequent and systematic occurrences of certain sequence types, particularly those containing CCTGT in the first 'loop' position. The study highlights the importance of identifying biologically relevant quadruplex sequences, which may serve as therapeutic targets. The analysis revealed that while many sequences do not form stable quadruplexes, some, such as those containing CCTGT and CCTGTCAT, stand out due to their frequency and potential functionality. The results also showed that the distribution of loop sequences within quadruplexes can provide insights into their stability and function. The study emphasizes the need for further experimental validation to correlate the occurrence of these sequences with biological functions, such as RNA expression levels and protein interactions.