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Updated: Apr 30, 2026

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Identification and Classification of Functional Split G-Quadruplexes Using Machine Learning-Guided Activity

Pranotosh Das1,2, Avimanyu Das1,2, Manish Debnath1,2

  • 1Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.

ACS Applied Bio Materials
|May 26, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a method to identify functional split G-quadruplexes for biosensing. Machine learning predicts their activity, enabling better diagnostics and overcoming function loss in split G-quadruplexes.

Keywords:
DNAzymemachine learningmolecular diagnosticsphase separationsplit G-quadruplex

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nanotechnology

Background:

  • Split G-quadruplexes show promise for biosensing and diagnostics.
  • However, splitting often results in reduced functionality, limiting their application.
  • Developing methods to identify and engineer functional split G-quadruplexes is crucial.

Purpose of the Study:

  • To identify and classify functional split G-quadruplexes.
  • To investigate the relationship between structural changes, phase separation, and functional activity.
  • To establish a predictive framework for engineering active split G-quadruplexes.

Main Methods:

  • Design and synthesis of split G-quadruplexes.
  • Characterization using fluorescence spectroscopy, microscopy, UV-vis spectroscopy, and circular dichroism.
  • Application of multivariate analysis and machine learning for pattern recognition and activity screening.

Main Results:

  • Structural changes in split G-quadruplexes correlate with phase separation.
  • Phase-separated condensates enhance fluorogenic and DNAzyme activity.
  • Machine learning successfully screened and classified split G-quadruplexes by functional activity.

Conclusions:

  • An integrative approach combining structural analysis and machine learning can predict split G-quadruplex function.
  • This framework facilitates the engineering of active split G-quadruplexes.
  • The study establishes a platform for advancing molecular diagnostics using functional split G-quadruplexes.