Abstract
Disseminated (DTCs) and circulating tumor cells (CTCs) are rare but pivotal in understanding cancer metastasis and advancing liquid biopsy-based diagnostics. Traditional detection approaches, hindered by their dependency on epithelial markers or morphological features, impair the accurate identification of varied DTC/CTC phenotypes within liquid biopsies. We describe DTCFinder, a bench-to-bits, label-free method integrating high-throughput single-cell RNA sequencing and machine learning, enabling unbiased detection, in-depth molecular characterization, and precise tissue-of-origin tracing of DTCs/CTCs across various types of liquid biopsies, even with ultra-scarce DTC/CTC presence in peripheral blood and low sequencing depth. DTCFinder offers a robust and versatile toolkit for liquid biopsy-based cancer diagnostics, enhancing our understanding of cancer metastasis.