CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.
We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios. CancerLocator also achieves promising results on patient plasma samples with low DNA methylation sequencing coverage.
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Shuli
S
Kang
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Qingjiao
Q
Li
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Quan
Q
Chen
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.|Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
Yonggang
Y
Zhou
Division of Pulmonary, Critical Care Medicine, Clinical Immunology and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Stacy
S
Park
VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Gina
G
Lee
Division of Pulmonary, Critical Care Medicine, Clinical Immunology and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Brandon
B
Grimes
Division of Pulmonary, Critical Care Medicine, Clinical Immunology and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
Kostyantyn
K
Krysan
Department of Stem Cell Biology and Regenerative Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
Min
M
Yu
Clinical Laboratory, Zhejiang Province Tongde Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
Wei
W
Wang
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Frank
F
Alber
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
Fengzhu
F
Sun
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.|Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.|Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.|Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.
Steven M
SM
Dubinett
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA. WenyuanLi@mednet.ucla.edu.
Wenyuan
W
Li
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA. XJZhou@mednet.ucla.edu.|Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, CA, 90095, USA. XJZhou@mednet.ucla.edu.
Xianghong Jasmine
XJ
Zhou
D000465:Algorithms; D003198:Computer Simulation; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015203:Reproducibility of Results; D057188:Workflow
D004273:DNA, Neoplasm
Cancer diagnosis; Cell-free DNA; DNA methylation; Liquid biopsy; Next-generation sequencing