In the journey of cancer treatment, early detection has always been a challenging issue. In recent years, liquid biopsy technology has gained widespread attention due to its non-invasive nature and high sensitivity. However, existing detection technologies often rely on deep targeted sequencing, making it difficult to integrate multiple data types, which in turn affects sensitivity and specificity.
To address this technical shortcoming, a research team from the University of Oxford has developed a novel multimodal circulating tumor DNA (ctDNA) detection method based on whole-genome TET-assisted pyridine boronate sequencing (TAPS). The highlight of this method is its ability to simultaneously analyze genomic and methylation data, achieving a sensitivity of 94.9% and a specificity of 88.8% for cancer diagnosis. This groundbreaking technology offers new possibilities for early cancer screening and patient stratification.
The study, titled "Multimodal cell-free DNA whole-genome TAPS is sensitive and reveals specific cancer signals," was published on January 8, 2025, in the journal Nature Communications. The research background indicates that although early cancer detection is crucial for improving patient prognosis, current screening methods cover less than 30% of cancer types, and many require invasive procedures, which have low acceptance rates. While multi-cancer early detection technologies can achieve non-invasive testing, they often have high false positive rates in asymptomatic populations, limiting their application.
The Oxford team's TAPS technology maintains high sensitivity at low ctDNA concentrations through a non-destructive method. Researchers validated the accuracy of this method across various cancer types by performing deep sequencing on samples from 61 cancer patients and 30 non-cancer controls.
The team also developed a multimodal data analysis process that integrates copy number variations, somatic mutations, and methylation signals to enhance the sensitivity of ctDNA detection. Results show that this method achieved a detection sensitivity of 85.2% in clinical samples, far exceeding the results from single data modalities.
Despite the significant advantages of this method in early cancer detection and postoperative monitoring, it still faces challenges in practical application, such as high sequencing costs and resource-limited clinical environments. Future research could further optimize sequencing technologies to expand its applicability across more cancer types.