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Nucleic Acids Res. 2019 May 7;47(8):e45. doi: 10.1093/nar/gkz096.

DriverML: a machine learning algorithm for identifying driver genes in cancer sequencing studies.

Author information

1
Center for Uterine Cancer Diagnosis and Therapy Research of Zhejiang Province, Women's Reproductive Health Key Laboratory of Zhejiang Province, Women's Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.
2
Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
3
Graduate Institute of Biomedical Sciences, Research Center for Tumor Medical Science, and Drug Development Center, China Medical University, Taichung 40402, Taiwan.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
5
Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui 230026, China.
6
Department of Mathematics, Zhejiang University, Hangzhou, Zhejiang 310027, China.

Abstract

Although rapid progress has been made in computational approaches for prioritizing cancer driver genes, research is far from achieving the ultimate goal of discovering a complete catalog of genes truly associated with cancer. Driver gene lists predicted from these computational tools lack consistency and are prone to false positives. Here, we developed an approach (DriverML) integrating Rao's score test and supervised machine learning to identify cancer driver genes. The weight parameters in the score statistics quantified the functional impacts of mutations on the protein. To obtain optimized weight parameters, the score statistics of prior driver genes were maximized on pan-cancer training data. We conducted rigorous and unbiased benchmark analysis and comparisons of DriverML with 20 other existing tools in 31 independent datasets from The Cancer Genome Atlas (TCGA). Our comprehensive evaluations demonstrated that DriverML was robust and powerful among various datasets and outperformed the other tools with a better balance of precision and sensitivity. In vitro cell-based assays further proved the validity of the DriverML prediction of novel driver genes. In summary, DriverML uses an innovative, machine learning-based approach to prioritize cancer driver genes and provides dramatic improvements over currently existing methods. Its source code is available at https://github.com/HelloYiHan/DriverML.

PMID:
30773592
PMCID:
PMC6486576
DOI:
10.1093/nar/gkz096
[Indexed for MEDLINE]
Free PMC Article

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