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Genome Biol. 2017 Mar 24;18(1):53. doi: 10.1186/s13059-017-1191-5.

CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.

Author information

1
Molecular and Computational Biology, University of Southern California, Los Angeles, CA, 90089, USA.
2
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
3
Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
4
Division of Pulmonary, Critical Care Medicine, Clinical Immunology and Allergy, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.
5
VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
6
Department of Stem Cell Biology and Regenerative Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90033, USA.
7
Clinical Laboratory, Zhejiang Province Tongde Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
8
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.
9
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.
10
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.
11
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, 90095, USA. sdubinett@mednet.ucla.edu.
12
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.
13
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.
14
Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, CA, 90095, USA. XJZhou@mednet.ucla.edu.

Abstract

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.

KEYWORDS:

Cancer diagnosis; Cell-free DNA; DNA methylation; Liquid biopsy; Next-generation sequencing

PMID:
28335812
PMCID:
PMC5364586
DOI:
10.1186/s13059-017-1191-5
[Indexed for MEDLINE]
Free PMC Article

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