# Detecting polynucleotide motifs: Pentads, hexads, and beyond

## TL;DR

This paper introduces a new tool for identifying complex nucleic acid structures called polyads, which are important for genome regulation and stability.

## Contribution

The novel contribution is the development and validation of LinkTetrado, a computational tool for detecting and classifying polyadic nucleic acid motifs.

## Key findings

- LinkTetrado identified 25 unique structures containing polyadic motifs in a dataset of 529 nucleic acid structures.
- Manual validation confirmed the accuracy of motif assignments with a precision of 0.87.
- Previously unreported pentads, hexads, heptads, and octads were found in both DNA and RNA.

## Abstract

The structural diversity of nucleic acids extends far beyond the canonical Watson–Crick base pairing, encompassing higher-order motifs, such as triads, tetrads, pentads, hexads, heptads, and octads, which play critical roles in genome regulation and stability. Among these, tetrads – forming the core of G-quadruplexes – and their polyadic extensions have emerged as key determinants in fundamental processes ranging from replication and transcription to telomere maintenance. However, the detection and characterization of these complex motifs in experimental structures remain challenging. To address this, we present LinkTetrado, a computational tool for the automated identification and classification of polyadic motifs in nucleic acid 3D structures. Applied to a curated dataset of 529 nucleic acid structures, LinkTetrado identified 25 unique structures containing such motifs, including previously unreported pentads, hexads, heptads, and octads in both DNA and RNA. Manual validation using NMR restraints and chemical shift data confirmed the accuracy of motif assignments and underscored the importance of integrating experimental evidence for reliable detection. LinkTetrado achieves a precision of 0.87 in identifying polyads. The tool is freely available at https://github.com/michal-zurkowski/linktetrado and provides a foundation for the systematic exploration of higher-order nucleic acid motifs.