Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis

Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring. ‘Circulating cell-free DNA can be used to predict cancer, but it is more challenging to assess in early stage cancer. Here, the authors created a diagnostic model using tumor fractions deciphered from circulating cfDNA methylation signatures, which exhibited an 86% sensitivity in detecting early-stage cancer.