Identifying Network Subgraph-Associated Essential Genes in Molecular Networks
Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 0
 Juhas, M., L. Eberl, and J.I. Glass, Essence of life: essential genes of minimal genomes. Trends Cell Biol, 2011. 21(10): p. 562-8.
 Chen, W.-H., et al., OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines. Nucleic Acids Research, 2016. 45(D1): p. D940-D944.
 Zhan, T. and M. Boutros, Towards a compendium of essential genes - From model organisms to synthetic lethality in cancer cells. Critical reviews in biochemistry and molecular biology, 2016. 51(2): p. 74-85.
 Gilvary, C., et al., A machine learning approach predicts essential genes and pharmacological targets in cancer. 2019, bioRxiv.
 Pertesi, M., et al., Essential genes shape cancer genomes through linear limitation of homozygous deletions. Communications Biology, 2019. 2(1): p. 262.
 Patel, S.J., et al., Identification of essential genes for cancer immunotherapy. Nature, 2017. 548(7669): p. 537-542.
 Dickerson, J.E., et al., Defining the role of essential genes in human disease. PloS one, 2011. 6(11): p. e27368-e27368.
 Zhang, R., H.Y. Ou, and C.T. Zhang, DEG: a database of essential genes. Nucleic Acids Research, 2004. 32(suppl_1): p. D271-D272.
 Huang, C.-H., et al., Computational analysis of molecular networks using spectral graph theory, complexity measures and information theory. bioRxiv, 2019: p. 536318.
 Mowshowitz, A., Entropy and the complexity of graphs: II. The information content of digraphs and infinite graphs. The bulletin of mathematical biophysics, 1968. 30(2): p. 225-240.
 Lee, C.H. Huang, and K.L. Ng, In silico study of significant network motifs in the cancer networks. Master’s thesis, National Formosa University, Taiwan., 2016.
 Hsieh, W.T., et al., Transcription factor and microRNA-regulated network motifs for cancer and signal transduction networks. BMC Syst Biol, 2015. 9 Suppl 1: p. S5.
 Nakaya, A., et al., KEGG OC: a large-scale automatic construction of taxonomy-based ortholog clusters. Nucleic Acids Res, 2013. 41(Database issue): p. D353-7.
 Nishida, K., et al., KEGGscape: a Cytoscape app for pathway data integration. F1000Res, 2014. 3: p. 144.
 Arakelyan, A. and L. Nersisyan, KEGGParser: parsing and editing KEGG pathway maps in Matlab. Bioinformatics, 2013. 29(4): p. 518-9.
 Alon, U., An Introduction to Systems Biology: design principles of biological circuits. 2006: Chapman and Hall/CRC.
 Shen-Orr, S.S., et al., Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genetics, 2002. 31(1): p. 64-68.
 Chan, S.W., et al., The Hippo pathway in biological control and cancer development. J Cell Physiol, 2011. 226(4): p. 928-39.
 Pan, D., Hippo signaling in organ size control. Genes Dev, 2007. 21(8): p. 886-97.
 Boopathy, G.T.K. and W. Hong, Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis. Frontiers in Cell and Developmental Biology, 2019. 7(49).
 Karin, M., et al., NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer, 2002. 2(4): p. 301-10.
 Park, M.H. and J.T. Hong, Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches. Cells, 2016. 5(2).
 Baker, R.G., M.S. Hayden, and S. Ghosh, NF-κB, inflammation, and metabolic disease. Cell Metab, 2011. 13(1): p. 11-22.
 Sabir, J.S.M., et al., Dissecting the Role of NF-κb Protein Family and Its Regulators in Rheumatoid Arthritis Using Weighted Gene Co-Expression Network. Frontiers in Genetics, 2019. 10(1163).
 Yamashita, M. and E. Passegué, TNF-α Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration. Cell Stem Cell, 2019. 25(3): p. 357-372.e7.
 Sun, S.-C., Non-canonical NF-κB signaling pathway. Cell research, 2011. 21(1): p. 71-85.
 Hayden, M.S. and S. Ghosh, Regulation of NF-κB by TNF family cytokines. Seminars in immunology, 2014. 26(3): p. 253-266.
 Yilmaz, A., et al., Defining essential genes for human pluripotent stem cells by CRISPR-Cas9 screening in haploid cells. Nat Cell Biol, 2018. 20(5): p. 610-619.
 Yu, L., et al., A survey of essential gene function in the yeast cell division cycle. Molecular biology of the cell, 2006. 17(11): p. 4736-4747.
 Zaenudin, E., et al., A Parallel Algorithm to Generate Connected Network Motifs IAENG International Journal of Computer Science, 2019 46(4): p. pp518-523.