The paper by Huppert and Balasubramanian investigates the prevalence and characteristics of G-quadruplexes in the human genome. G-quadruplexes are four-stranded structures formed by guanine-rich DNA sequences, which have been implicated in various biological processes and diseases. The authors present a working rule to predict which DNA sequences can form these structures and describe a search algorithm, quadparser, to identify such sequences in genomic DNA. They count the number of quadruplexes in the human genome and compare it with predictions from models that treat DNA as a Bernoulli stream or a Markov chain. The results show that the distribution of loop lengths is significantly different from random, indicating the presence of potentially relevant quadruplex-forming sequences. Notably, there is a significant repression of quadruplexes in exonic regions, suggesting that quadruplex-forming patterns are disfavored in sequences that will form RNA. The study also highlights the importance of loop length correlations in quadruplexes, which could be a mechanism for reducing their formation. Overall, the findings suggest that G-quadruplexes play a significant role in the human genome and may have functional implications in gene regulation and other cellular activities.The paper by Huppert and Balasubramanian investigates the prevalence and characteristics of G-quadruplexes in the human genome. G-quadruplexes are four-stranded structures formed by guanine-rich DNA sequences, which have been implicated in various biological processes and diseases. The authors present a working rule to predict which DNA sequences can form these structures and describe a search algorithm, quadparser, to identify such sequences in genomic DNA. They count the number of quadruplexes in the human genome and compare it with predictions from models that treat DNA as a Bernoulli stream or a Markov chain. The results show that the distribution of loop lengths is significantly different from random, indicating the presence of potentially relevant quadruplex-forming sequences. Notably, there is a significant repression of quadruplexes in exonic regions, suggesting that quadruplex-forming patterns are disfavored in sequences that will form RNA. The study also highlights the importance of loop length correlations in quadruplexes, which could be a mechanism for reducing their formation. Overall, the findings suggest that G-quadruplexes play a significant role in the human genome and may have functional implications in gene regulation and other cellular activities.