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

Shuli Kang; Qingjiao Li; Quan Chen; Yonggang Zhou; Stacy Park; Gina Lee; Brandon Grimes; Kostyantyn Krysan; Min Yu; Wei Wang; Frank Alber; Fengzhu Sun; Steven M Dubinett; Wenyuan Li; Xianghong Jasmine Zhou

doi:10.1186/s13059-017-1191-5

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

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

Authors

Shuli Kang¹, Qingjiao Li¹, Quan Chen¹, Yonggang Zhou^{2

3}, Stacy Park⁴, Gina Lee⁵, Brandon Grimes⁴, Kostyantyn Krysan⁴, Min Yu⁶, Wei Wang⁷, Frank Alber¹, Fengzhu Sun¹, Steven M Dubinett^{8

9

10

11}, Wenyuan Li¹², Xianghong Jasmine Zhou^{13

14}

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Algorithms
Computer Simulation
CpG Islands
DNA Methylation*
DNA, Neoplasm / blood
DNA, Neoplasm / genetics
Epigenesis, Genetic*
Epigenomics / methods*
Humans
Models, Statistical
Neoplasms / diagnosis*
Neoplasms / genetics*
Reproducibility of Results
Workflow

Substances

DNA, Neoplasm

Abstract

Publication types

MeSH terms

Substances

Grants and funding