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

Abstract 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.