# Beyond Binary: A Machine Learning Framework for Interpreting Organismal Behavior in Cancer Diagnostics

**Authors:** Aya Hasan Alshammari, Monther F. Mahdi, Takaaki Hirotsu, Masayo Morishita, Hideyuki Hatakeyama, Eric di Luccio

PMC · DOI: 10.3390/biomedicines13102409 · Biomedicines · 2025-09-30

## TL;DR

This paper proposes a new machine learning framework to improve cancer diagnostics using organismal behavior and neural responses to cancer-related chemicals.

## Contribution

The Dual-Pathway Framework combines high-throughput screening with machine learning for cancer subtyping and monitoring.

## Key findings

- C. elegans chemotaxis assays achieved 87–96% sensitivity and 90–95% specificity in cancer detection.
- Trained canines and AI-augmented systems achieved ~94–95% accuracy in prostate cancer detection.
- Insects like locusts and honeybees can classify VOCs with 82–100% accuracy in under 250 ms.

## Abstract

Organismal biosensing leverages the olfactory acuity of living systems to detect volatile organic compounds (VOCs) associated with cancer, offering a low-cost and non-invasive complement to conventional diagnostics. Early studies demonstrate its feasibility across diverse platforms. In C. elegans, chemotaxis assays on urine samples achieved sensitivities of 87–96% and specificities of 90–95% in case–control cohorts (n up to 242), while calcium imaging of AWC neurons distinguished breast cancer urine with ~97% accuracy in a small pilot cohort (n ≈ 40). Trained canines have identified prostate cancer from urine with sensitivities of ~71% and specificities of 70–76% (n ≈ 50), and AI-augmented canine breath platforms have reported accuracies of ~94–95% across ~1400 participants. Insects such as locusts and honeybees enable ultrafast neural decoding of VOCs, achieving 82–100% classification accuracy within 250 ms in pilot studies (n ≈ 20–30). Collectively, these platforms validate the principle that organismal behavior and neural activity encode cancer-related VOC signatures. However, limitations remain, including small cohorts, methodological heterogeneity, and reliance on binary outputs. This review proposes a Dual-Pathway Framework, where Pathway 1 leverages validated indices (e.g., the Chemotaxis Index) for high-throughput screening, and Pathway 2 applies machine learning to high-dimensional behavioral vectors for cancer subtyping, staging, and monitoring. By integrating these approaches, organismal biosensing could evolve from proof-of-concept assays into clinically scalable precision diagnostics.

## Linked entities

- **Diseases:** cancer (MONDO:0004992), breast cancer (MONDO:0004989), prostate cancer (MONDO:0005159)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** Cancer (MESH:D009369), prostate cancer (MESH:D011471), breast cancer (MESH:D001943)
- **Chemicals:** calcium (MESH:D002118), VOCs (MESH:D055549)
- **Species:** Apis mellifera (bee, species) [taxon 7460], Homo sapiens (human, species) [taxon 9606], C. elegans [taxon 328850], Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12561682/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12561682/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12561682/full.md

---
Source: https://tomesphere.com/paper/PMC12561682