Identification of the Key Genes of Autism Spectrum Disorder Through Protein-Protein Interaction Network
DOI:
https://doi.org/10.31661/gmj.v8i.1367Keywords:
Autism Spectrum Disorder, Transcriptome, Protein Interaction Maps, Gene OntologyAbstract
Background: Currently, the prevalence of autism spectrum disorder (ASD) is increasing, which widely spurs the interest in the molecular investigation. Thereby, a better understanding of the given disorder mechanisms is likely to be achieved. Bioinformatics suiting protein-protein interactions analysis via the application of high-throughput studies, such as protein array, is one of these achievements.Materials and Methods: The gene expression data from Gene Expression Omnibus (GEO) database were downloaded, and the expression profile of patients with developmental delay and autistic features were analyzed via Cytoscape and its relevant plug-ins.Results: Our findings indicated that EGFR, ACTB, RHOA, CALM1, MAPK1, and JUN genes as the hub-bottlenecks and their related terms could be important in ASD risk. In other words, any expression modification in these genes could trigger dysfunctions in the corresponding biological processes.Conclusion: We suggest that differentially expressed genes could be used as suitable targets for ASD after being validated.[GMJ.2019;8:e1367]
References
Ngounou Wetie AG, Wormwood KL, Russell S, Ryan JP, Darie CC, Woods AG. A pilot proteomic analysis of salivary biomarkers in autism spectrum disorder. Autsim Res.2015;8(3):338-50. https://doi.org/10.1002/aur.1450PMid:25626423 Loth E, Spooren W, Ham LM, Isaac MB, Auriche-Benichou C, Banaschewski T et al. Identification and validation of biomarkers for autism spectrum disorders. Nat Rev Drug Discov. 2016;15(1):70-3. https://doi.org/10.1038/nrd.2015.7PMid:26718285 Guney E, Iseri E. Genetic and environmental factors in autism. Recent Advances in Autism Spectrum Disorders-Volume I. InTech; 2013. 321-31. https://doi.org/10.5772/53295 Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder. Mol Diagn Ther. 2018; 22(5):1-23. https://doi.org/10.1007/s40291-018-0352-xPMid:30039193 PMCid:PMC6132446 Bazelmans T, Jones EJ, Ghods S, Corrigan S, Toth K, Charman T et al. Heart rate mean and variability as a biomarker for phenotypic variation in preschoolers with autism spectrum disorder. Autism Res. 2018;70-3. https://doi.org/10.1002/aur.1982 Sayehmiri F, Babaknejad N, Bahrami S, Sayehmiri K, Darabi M, Rezaei-Tavirani M. Zn/Cu levels in the field of autism disorders: a systematic review and meta-analysis. Iran J Child Neurol. 2015;9(4):1-9. PMid:26664435 PMCid:PMC4670971 Hwang BJ, Mohamed MA, BraÅ¡ić JR. Molecular imaging of autism spectrum disorder. Int Rev Psychiatry. 2017;29(6):530-54. https://doi.org/10.1080/09540261.2017.1397606PMid:29231773 Klin A. Biomarkers in Autism Spectrum Disorder: Challenges, Advances, and the Need for Biomarkers of Relevance to Public Health. Focus. 2018;16(2):135-42. https://doi.org/10.1176/appi.focus.20170047 Howsmon DP, Adams JB, Kruger U, Geis E, Gehn E, Hahn J. Erythrocyte fatty acid profiles in children are not predictive of autism spectrum disorder status: a case control study. Biomarker Res. 2018;6(1):1-9. https://doi.org/10.1186/s40364-018-0125-zPMid:29568526 PMCid:PMC5853097 Amal H, Barak B, Bhat V, Gong G, Joughin BA, Wishnok JS et al. Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function. Mol psychiatry. 2018:1. https://doi.org/10.1038/s41380-018-0113-6 Eun JW, Yang HD, Kim SH, Hong S, Park KN, Nam SW et al. Identification of novel biomarkers for prediction of neurological prognosis following cardiac arrest. Oncotarget. 2017;8(10):16144-157. https://doi.org/10.18632/oncotarget.14877PMid:28147324 PMCid:PMC5369953 Atan NAD, Koushki M, Tavirani MR, Ahmadi NA. Protein-Protein Interaction Network Analysis of Salivary Proteomic Data in Oral Cancer Cases. Asian Pac J Cancer Prev. 2018; 19(6): 1639–45. PMCid:PMC6103602 Azodi MZ, Rezaei-Tavirani M, Nejad MR, Rezaei-Tavirani M. Human Prolactinoma: A View of Protein-Protein Interaction Pattern. Int J Endocrinol Metab Disord. 2018; 16(4): 1-6. Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010;27(3):431-2. https://doi.org/10.1093/bioinformatics/btq675PMid:21149340 PMCid:PMC3031041 Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 2017; 45: 362–68. https://doi.org/10.1093/nar/gkw937PMid:27924014 PMCid:PMC5210637 Safari-Alighiarloo N, Rezaei-Tavirani M, Taghizadeh M, Tabatabaei SM, Namaki S. Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis. PeerJ. 2016;4:1-22. https://doi.org/10.7717/peerj.2775PMid:28028462 PMCid:PMC5183126 Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics. 2013;29(5):661-3. https://doi.org/10.1093/bioinformatics/btt019PMid:23325622 PMCid:PMC3582273 Woods AG, Wetie AGN, Sokolowska I, Russell S, Ryan JP, Michel TM et al. Mass spectrometry as a tool for studying autism spectrum disorder. J mol psychiatry. 2013;1(1):1-10. https://doi.org/10.1186/2049-9256-1-6PMid:25408899 PMCid:PMC4223881 Azodi MZ, Tavirani MR, Oskouie AA, Mansouri V, Hamdieh M, Nejati N et al. Introducing Transthyretin as a Differentially Expressed Protein in Washing Subtype of Obsessive-Compulsive Disorder. Basic Clin Neurosci. 2018;9(3):187-194. https://doi.org/10.29252/nirp.bcn.9.3.187PMid:30034649 PMCid:PMC6037430 Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304(5676):1497-500. https://doi.org/10.1126/science.1099314PMid:15118125 Rivière J-B, Van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C et al. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nature genetics. 2012;44(4):1-17. https://doi.org/10.1038/ng.1091 Gou L, Wang W, Tong A, Yao Y, Zhou Y, Yi C et al. Proteomic identification of RhoA as a potential biomarker for proliferation and metastasis in hepatocellular carcinoma. J Mol Med. 2011;89(8):817-27. https://doi.org/10.1007/s00109-011-0753-3PMid:21475975 Guo C, Liu S, Wang J, Sun M-Z, Greenaway FT. ACTB in cancer. Clin. Chim. Acta. 2013;417:39-44. https://doi.org/10.1016/j.cca.2012.12.012PMid:23266771 Zhang Y, Gu Z, Qiu G. The association study of calmodulin 1 gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. BioMed Res Int. 2014;2014:1-8. https://doi.org/10.1155/2014/168106 Yiwei T, Hua H, Hui G, Mao M, Xiang L. HOTAIR interacting with MAPK1 regulates ovarian cancer skov3 cell proliferation, migration, and invasion. Med Sci Monit. 2015;21:1856- 63. https://doi.org/10.12659/MSM.893528PMid:26117268 PMCid:PMC4489685 Saunders F, Yoshida K, Barr R, Macdonald H, Reid D, Aspden R et al. Biomarkers of osteoarthritis progression. Osteoarthr Cartil. 2013;21:78. https://doi.org/10.1016/j.joca.2013.02.171 Prusty BK, Das BC. Constitutive activation of transcription factor APâ€1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and APâ€1 activity in HeLa cells by curcumin. ‎Int. J. Cancer. 2005;113(6):951-60. https://doi.org/10.1002/ijc.20668PMid:15514944 Russo AJ. Increased epidermal growth factor receptor (EGFR) associated with hepatocyte growth factor (HGF) and symptom severity in children with autism spectrum disorders (ASDs). J Cent Nerv Syst Dis. 2014;6: 79-83. https://doi.org/10.4137/JCNSD.S13767PMid:25249767 PMCid:PMC4167315 Russo AJ. Decreased phosphorylated protein kinase B (Akt) in individuals with autism associated with high epidermal growth factor receptor (EGFR) and low gamma-aminobutyric acid (GABA). Biomark insights. 2015;10: 89-94. https://doi.org/10.4137/BMI.S21946PMid:26508828 PMCid:PMC4607071 Goitia V, Oquendo M, Stratton R. Case of 7p22. 1 microduplication detected by whole genome microarray (REVEAL) in workup of child diagnosed with autism. Case Rep Genet. 2015;2015. 1-6. Cuvertino S, Stuart HM, Chandler KE, Roberts NA, Armstrong R, Bernardini L et al. ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder. Am. J. Hum. Genet.2017;101(6):1021-33. https://doi.org/10.1016/j.ajhg.2017.11.006PMid:29220674 PMCid:PMC5812896 Gilbert J, Man H-Y. Fundamental elements in autism: from neurogenesis and neurite growth to synaptic plasticity. FRONT CELL NEUROSCI. 2017;11:1-25. https://doi.org/10.3389/fncel.2017.00359PMid:29209173 PMCid:PMC5701944 Packer A. Rho family of enzymes at crossroads of autism. 2013. Wagle M-C, Kirouac D, Klijn C, Liu B, Mahajan S, Junttila M et al. A transcriptional MAPK Pathway Activity Score (MPAS) is a clinically relevant biomarker in multiple cancer types. NPJ Precis Oncol.. 2018;2(1):7. 1-12. Wei H, Alberts I, Li X. The apoptotic perspective of autism. Int J Dev Neurosci. 2014;36:13-8. https://doi.org/10.1016/j.ijdevneu.2014.04.004PMid:24798024 Calabrò M, Mandelli L, Crisafulli C, Sidoti A, Jun T-Y, Lee S-J et al. Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1. Neuropsychobiology. 2016;74(3):159-68. https://doi.org/10.1159/000468543PMid:28494468 Ernst C. Proliferation and differentiation deficits are a major convergence point for neurodevelopmental disorders. Trends neurosci. 2016;39(5):290-9. https://doi.org/10.1016/j.tins.2016.03.001PMid:27032601 Upadhya D, Ogata M, Reneker LW. MAPK1 is required for establishing the pattern of cell proliferation and for cell survival during lens development. Development. 2013;140(7):1573-82. https://doi.org/10.1242/dev.081042PMid:23482492 PMCid:PMC3596996 Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat. Cell Biol.2002;4(5):131-6. https://doi.org/10.1038/ncb0502-e131PMid:11988758
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