Abstract
Cancer driver gene is a type of gene with abnormal alterations that initiate or promote tumorigenesis. Driver genes can be used to reveal the fundamental pathological mechanisms of tumorigenesis. These genes may have pathological changes at different omics levels. Thus, identifying cancer driver genes involving two or more omics levels is essential. In this study, a computational investigation was conducted on lung cancer driver genes. Four omics levels, namely, epigenomics, genomics, transcriptomics, and post-transcriptomics, were involved. From the driver genes at each level, the Laplacian heat diffusion algorithm was executed on a protein–protein interaction network for discovering latent driver genes at this level. A following screen procedure was performed to extract essential driver genes, which contained three tests: permutation, association, and function tests, which can exclude false-positive genes and screen essential ones. Finally, the intersection operation was performed to obtain novel driver genes involving two omic levels. The analyses on obtained genes indicated that they were associated with fundamental pathological mechanisms of lung cancer at two corresponding omics levels.
Highlights
Driver gene is a commonly used description in oncology to describe genes with abnormal alterations that initiate or promote tumorigenesis (Pao and Girard, 2011; Tokheim et al, 2016)
In the first stage of Laplacian heat diffusion (LHD)-based method, some latent driver genes were identified for each omics level
153 validated driver genes were fed into the LHD algorithm, which was executed on the protein–protein interaction (PPI) network N
Summary
Driver gene is a commonly used description in oncology to describe genes with abnormal alterations that initiate or promote tumorigenesis (Pao and Girard, 2011; Tokheim et al, 2016). Identifying driver genes can help us reveal the fundamental pathological mechanisms of tumorigenesis (Pao and Girard, 2011). Identification of Cancer Driver Genes techniques is time consuming but can detect all pathological alterations associated with tumorigenesis. Genes that are mutated or abnormally regulated during tumorigenesis but not associated with the initiation or progression of tumors are summarized as passenger genes (Pon and Marra, 2015). Most of the genes altered during tumorigenesis are passenger genes, which cannot help us understand or reveal the pathological mechanisms of cancer. The identification of driver genes is one of the major research directions in oncology
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