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Deep learning-based real-time detection of novel pathogens during sequencing.

Jakub M Bartoszewicz1, Ulrich Genske1, Bernhard Y Renard1

  • 1Digital Engineering Faculty, Hasso Plattner Institute, University of Postdam, Prof.-Dr.-Helmert-Straße 2-3, 14482 Brandenburg, Germany.

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Rapid pathogen detection is crucial for pandemic prevention. New machine learning models predict pathogenic potential from very short DNA sequences in real-time, significantly improving early outbreak detection.

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Area of Science:

  • Genomics and Bioinformatics
  • Pathogen Detection
  • Machine Learning in Biology

Background:

  • Emerging infectious diseases pose significant global health risks.
  • Next-generation sequencing (NGS) is vital for early pathogen identification.
  • Current real-time analysis tools struggle with novel or unknown pathogens.

Purpose of the Study:

  • To develop a real-time pathogenic potential prediction workflow.
  • To identify the minimum sequence length required for accurate pathogen inference.
  • To improve early detection capabilities for novel and unknown pathogens.

Main Methods:

  • Trained deep neural networks to classify short DNA reads from Illumina and Nanopore sequencing.
  • Integrated classification models with HiLive2, a real-time Illumina mapper.
  • Evaluated performance on simulated and real-world data, including SARS-CoV-2.

Main Results:

  • Achieved an 80-fold sensitivity increase after only 50 Illumina cycles compared to real-time mapping.
  • Demonstrated that the first 250 bp of Nanopore reads (0.5s) yield more accurate predictions than finished long reads.
  • Outperformed existing machine learning and sequence alignment methods on diverse datasets.

Conclusions:

  • Short subsequences are sufficient for accurate real-time pathogenic potential prediction.
  • The developed workflow significantly enhances early detection of unknown pathogens.
  • This approach has potential applications in biosecurity screening of synthetic sequences.