CancerDetector: Ultrasensitive and Non-Invasive Cancer Detection at the Resolution of Individual Reads using Cell-free DNA Methylation Sequencing Data

The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed “CancerDetector”, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation patterns of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor burden. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor DNAs. In addition, the predicted tumor burden showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1X to 10X). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 4 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004317	The blood samples of four liver cancer patients and four healthy people, and the solid liver tumor samples of two liver cancer patients are collected for this dataset. Blood samples were centrifuged first at 1,600 × g for 10 minutes, and then the plasma was transferred into new micro tubes and centrifuged at 16,000 × g for another 10 minutes. The plasma was collected and stored at -80⁰C. CfDNA was extracted from 5 ml plasma using the Qiagen QIAamp Circulating Nucleic Acids Kit and quantified by Qubit 3.0 Fluoromter (Thermo Fisher Scientific). Bisulfite conversion of cfDNA was performed by using EZ-DNA-Methylation-GOLD kit (Zymo Research). After that, Accel-NGS Methy-Seq DNA library kit (Swift Bioscience) was used to prepare the sequencing libraries. The DNA libraries were then sequenced with 150bp paired-end reads.	HiSeq X Ten	10

Publications	Citations
CancerDetector: ultrasensitive and non-invasive cancer detection at the resolution of individual reads using cell-free DNA methylation sequencing data. Li W, Li Q, Kang S, Same M, Zhou Y, Sun C, Liu CC, Matsuoka L, Sher L, Wong WH, Alber F, Zhou XJ. Nucleic Acids Res 46: 2018 e89	94
Leveraging locus-specific epigenetic heterogeneity to improve the performance of blood-based DNA methylation biomarkers. Miller BF, Pisanic Ii TR, Margolin G, Petrykowska HM, Athamanolap P, Goncearenco A, Osei-Tutu A, Annunziata CM, Wang TH, Elnitski L. Clin Epigenetics 12: 2020 154	6
DISMIR: Deep learning-based noninvasive cancer detection by integrating DNA sequence and methylation information of individual cell-free DNA reads. Li J, Wei L, Zhang X, Zhang W, Wang H, Zhong B, Xie Z, Lv H, Wang X. Brief Bioinform 22: 2021 bbab250	19
Cell-free DNA TAPS provides multimodal information for early cancer detection. Siejka-Zielińska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-Böckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX. Sci Adv 7: 2021 eabh0534	29