Circular RNA‐Based Molecular Computation Enhances Plasma Biomarker Detection in Biliary Tract Cancer

Molecular diagnosis of biliary tract cancer (BTC) remains a significant clinical challenge due to the lack of sensitive and specific diagnostic tools. Although large panels based on multi-biomarkers have demonstrated potential in enhancing diagnostic accuracy, their clinical application is hindered by complexity and high costs. To overcome these limitations, we have developed a DNA-based molecular computation system that integrates the detection of plasma circular RNAs (circRNAs) with molecular computation, enabling intelligent and rapid diagnosis of BTC. By identifying and validating a specific and small set of circRNA biomarkers that are differentially expressed in BTC patients, we designed a DNA computation framework that directly translates biomarker levels into diagnostic outcomes without the need of external analysis and interpretation. In a validation cohort of 70 individuals, our approach achieved a diagnostic accuracy of 83%, demonstrating its potential as a cost-effective and efficient tool for rapid diagnosis of BTC. This work highlights the potential of molecular computation in enhancing integrated and rapid cancer diagnostics, paving the way for clinical implementation.