QUFIND: tool for comparative prediction and mining of G4 quadruplexes overlapping with CpG islands

Abstract

G-quadruplexes (G4s) are secondary structures in DNA that have been shown to be involved in gene regulation. They play a vital role in the cellular processes and several pathogens including bacteria, fungi, and viruses have also been shown to possess G4s that help them in their pathogenesis. Additionally, cross-talk among the CpG islands and G4s has been shown to influence biological processes. The virus-encoded G4s are affected by the mutational landscape leading to the formation/deletion of these G4s. Therefore, understanding and predicting these multivariate effects on traditional and non-traditional quadruplexes forms an important area of research, that is, yet to be investigated. We have designed a user-friendly webserver QUFIND (http://soodlab.com/qufinder/) that can predict traditional as well as non-traditional quadruplexes in a given sequence. QUFIND is connected with ENSEMBL and NCBI so that the sequences can be fetched in a real-time manner. The algorithm is designed in such a way that the user is provided with multiple options to customize the base (A, T, G, or C), size of the stem (2–5), loop length (1–30), number of bulges (1–5) as well as the number of mismatches (0–2) enabling the identification of any of the secondary structure as per their interest. QUFIND is designed to predict both CpG islands as well as G4s in a given sequence. Since G4s are very short as compared to the CpG islands, hence, QUFIND can also predict the overlapping G4s within CpG islands. Therefore, the user has the flexibility to identify either overlapping or non-overlapping G4s along with the CpG islands. Additionally, one section of QUFIND is dedicated to comparing the G4s in two viral sequences. The visualization is designed in such a manner that the user is able to see the unique quadruplexes in both the input sequences. The efficiency of QUFIND is calculated on G4s obtained from G4 high throughput sequencing data (n = 1000) or experimentally validated G4s (n = 329). Our results revealed that QUFIND is able to predict G4-quadruplexes obtained from G4-sequencing data with 90.06% prediction accuracy whereas experimentally validated quadruplexes were predicted with 97.26% prediction accuracy.