Artificial Intelligence-Enhanced Analysis of Genomic DNA Visualized with Nanoparticle-Tagged Peptides under Electron Microscopy.

Journal: Small (Weinheim an der Bergstrasse, Germany)
PMID:

Abstract

DNA visualization has advanced across multiple microscopy platforms, albeit with limited progress in the identification of novel staining agents for electron microscopy (EM), notwithstanding its ability to furnish a broad magnification range and high-resolution details for observing DNA molecules. Herein, a non-toxic, universal, and simple method is proposed that uses gold nanoparticle-tagged peptides to stain all types of naturally occurring DNA molecules, enabling their visualization under EM. This method enhances the current DNA visualization capabilities, allowing for sequence-specific, genomic-scale, and multi-conformational visualization. Importantly, an artificial intelligence (AI)-enabled pipeline for identifying DNA molecules imaged under EM is presented, followed by classification based on their size, shape, or conformation, and finally, extraction of their significant dimensional features, which to the best of authors' knowledge, has not been reported yet. This pipeline strongly improved the accuracy of obtaining crucial information such as the number and mean length of DNA molecules in a given EM image for linear DNA (salmon sperm DNA) and the circumferential length and diameter for circular DNA (M13 phage DNA), owing to its image segmentation capability. Furthermore, it remained robust to several variations in the raw EM images arising from handling during the DNA staining stage.

Authors

  • Priyannth Ramasami Sundharbaabu
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.
  • Junhyuck Chang
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.
  • Yunchul Kim
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.
  • Youmin Shim
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.
  • Byoungsang Lee
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.
  • Chanyoung Noh
    Department of Chemistry & Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul, 04107, South Korea.
  • Sujung Heo
    Department of Chemistry & Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul, 04107, South Korea.
  • Seung Seo Lee
    School of Chemistry and Chemical Engineering, University of Southampton, Southampton, SO17 1BJ, UK.
  • Sang-Hee Shim
    Department of Chemistry, Korea University, Seoul, 02841, South Korea.
  • Kwang-Il Lim
    Department of Chemical and Biological Engineering, Sookmyung Women's University, Seoul, 04312, South Korea.
  • Kyubong Jo
    Department of Chemistry & Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul, 04107, South Korea.
  • Jung Heon Lee
    School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, South Korea.