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Computational Identification and Illustrative Standard for Representation of Unimolecular G-Quadruplex Secondary Structures (CIIS-GQ)

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Abstract

G-quadruplexes refer to a large group of nucleic acid–based structures. In recent years, they have been attracting attention due to their biological roles in the telomeres and promoter regions. These structures show wide diversity in topology, however, development of methods for structural classification of G-quadruplexes has been evaded for a long time. There has been a limited number of studies aiming to bring forth a secondary structure classification method. The situation was even more complex than imagined, since the discovery of bulged and mismatched G-quadruplexes while most of the available tools fail to distinguish these non-canonical G-quadruplex motifs. Moreover, the interpretation of their analysis output still requires expert knowledge. In this study, we propose a new method for identification of unimolecular G-Quadruplexes and classification by secondary structures based on three-dimensional structural data. Briefly, coordinates of guanines are processed to identify tetrads, loops and bulges. Then, we present the secondary structure in the form of a depiction which shows the loop types, bulges, and guanines that participate in each tetrad. Moreover, CIIS-GQ identifies non-guanine nucleotides that joins the G-tetrads and forms multiplets. Finally, the results of our study are compared with DSSR and ElTetrado classification methods, and the advantages of the proposed depiction method for representing secondary structures were discussed. The source code of the method can be accessed via https://github.com/TugayDirek/CIIS-GQ.

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Data Availability

The scripts and data are available at https://github.com/TugayDirek/CIIS-GQ

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Acknowledgements

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Funding

This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 216S854. The authors thank to TUBITAK for their supports.

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Authors and Affiliations

  1. Department of Software Engineering, Izmir University of Economics, İzmir, Turkey

    Tugay Direk

  2. Department of Biomedical Engineering, Izmir University of Economics, İzmir, Turkey

    Osman Doluca

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  1. Tugay Direk
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  2. Osman Doluca
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This work has been completed under the supervision of Osman Doluca, with the majority of the code base completed by Tugay Direk.

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Correspondence to Osman Doluca.

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Direk, T., Doluca, O. Computational Identification and Illustrative Standard for Representation of Unimolecular G-Quadruplex Secondary Structures (CIIS-GQ). J Comput Aided Mol Des 38, 35 (2024). https://doi.org/10.1007/s10822-024-00573-1

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