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Updated: Sep 18, 2025

Automatic Separation and Collection of Cancer-Related Substances from Clinical Samples
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Cluster-based human-in-the-loop strategy for improving machine learning-based circulating tumor cell detection in

Hümeyra Husseini-Wüsthoff1,2,3, Sabine Riethdorf4, Andreas Schneeweiss5

  • 1Institute for Applied Medical Informatics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Patterns (New York, N.Y.)
|June 27, 2025
PubMed
Summary

This study introduces a human-in-the-loop machine learning approach for accurately identifying circulating tumor cells (CTCs) in liquid biopsies. The method enhances accuracy and reduces expert evaluation time in metastatic cancer diagnostics.

Keywords:
CTCcirculating tumor cellsclusteringhuman-in-the-loopimage classificationlatent space analysisliquid biopsymachine learningmetastatic breast cancerself-supervision

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Area of Science:

  • Oncology
  • Biotechnology
  • Computational Biology

Background:

  • Liquid biopsy for metastatic cancer faces challenges in distinguishing circulating tumor cells (CTCs) from non-CTCs.
  • Current gold standard methods rely on laborious manual image analysis.
  • Machine learning (ML) shows promise for automation but requires expert input for uncertain predictions and limited data.

Purpose of the Study:

  • To develop an automated, human-in-the-loop ML system for improved CTC detection and differentiation.
  • To reduce the time and effort required for expert evaluation in liquid biopsy analysis.
  • To enhance classification performance using a targeted sampling strategy with limited labeled data.

Main Methods:

  • Combined self-supervised deep learning with a conventional ML classifier.
  • Implemented a human-in-the-loop strategy with targeted sampling from high-uncertainty clusters.
  • Iteratively refined the ML model by incorporating expert-labeled data.

Main Results:

  • Demonstrated feasibility on metastatic breast cancer patient data.
  • Achieved improved classification performance compared to traditional methods.
  • Significantly reduced expert evaluation time versus the CellSearch system.

Conclusions:

  • The proposed human-in-the-loop ML approach effectively improves CTC detection in liquid biopsies.
  • Targeted sampling strategies enhance ML model performance and reduce diagnostic workload.
  • This method offers a more efficient and accurate alternative to current gold standards for metastatic cancer analysis.