Protein-Protein Interaction Network Analysis Revealed a New Prospective of Posttraumatic Stress Disorder

Authors

  • Mostafa Rezaei Tavirani
  • Farshad Okhovatian
  • Mohammad Rostami-Nejad
  • Sina Rezaei Tavirani

DOI:

https://doi.org/10.31661/gmj.v7i.1137

Keywords:

Posttraumatic Stress Disorder, Protein-Protein Interaction Network, Cytoscape, ClueGO, Biomarker Panel

Abstract

Background: Posttraumatic stress disorder (PTSD) is known by a number of mental disorders, including recurring memories of trauma, mental appalling, and escaping of sign that make them recall the trauma in question. Clinical interviews serve as the main diagnostic tool for PTSD. With respect to treatment, either pharmacotherapy or psychotherapy or a combination of both is used as a therapeutic method for PTSD. In this study, a number of crucial genes related to PTSD, which can be considered as biomarker candidates, were represented. Materials and Methods: The genes related to PTSD were extracted from the STRING database and organized in a protein-protein interaction network with the help of Cytoscape software version 3.6.0. The network was analyzed, and the important genes were introduced based on central indices. The biological processes related to the crucial genes were enriched via gene ontology using ClueGO. Results: From a total of 100 genes, 63 genes were extracted that formed the main connected component, and of these, 12 crucial genes¾POMC, BDNF, FOS, NR3C1, CRH, IL6, NPS, HTR1A, NPY, CREB1, CRHR1, and TAC1¾were introduced. Biological processes were classified into the regulation of corticosterone, regulation of behavior, response to fungus, multicellular organism response to stress, and associative learning. Conclusion: The introduced 12 crucial genes can be used as a biomarker panel related to PTSD and can be considered as a diagnostic reagent or drug target; however, more investigations are needed to use these genes as biomarkers.[GMJ.2018;7:e1137]

References

Smith A, Ratanatharathorn A, Boks M, Logue M, Maihofer A, Kilaru V, et al. 86-Epigenetic signatures of PTSD: results from the psychiatric genomics consortium PTSD epigenetics workgroup. Biol Psychiatry. 2017; 81(10): S36. Busbee PB, Nagarkatti M, Nagarkatti P. Alterations in p53 expression in PMBCs of PTSD patients leads to dysregulation in miRNA biogenesis which promotes an inflammatory Th17 immune cell phenotype. Am Assoc Immnol. 2017; 198 (Suppl 1): 223-12. Marx BP, Engel-Rebitzer E, Bovin MJ, Parker-Guilbert KS, Moshier S, Barretto K, et al. The influence of veteran race and psychometric testing on veterans affairs posttraumatic stress disorder (PTSD) disability exam outcomes. Psychol Assess. 2017; 29(6):710-9. Lokshina Y, Liberzon I. Enhancing efficacy of PTSD treatment: role of circuits, genetics, and optimal timing. Clin Psychol (New York). 2017; 24(3): 298-301. Girgenti MJ, Hare BD, Ghosal S, Duman RS. Molecular and cellular effects of traumatic stress: Implications for PTSD. Curr psychiatry rep. 2017;19(11): 85. Chakraborty N, Meyerhoff J, Jett M, Hammamieh R. Genome to phenome: a systems biology approach to PTSD using an animal model. Methods Mol Biol. 2017; 1598: 117-54. Muhie S, Gautam A, Chakraborty N, Hoke A, Meyerhoff J, Hammamieh R, et al. Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder. Transl Psychiatry. 2017; 7(5): e1135. Matosin N, Cruceanu C. Stress-related memory impairments are modulated by the synergistic action of stress hormones: implications for PTSD. J Neurosci. 2017; 37(16): 4225-7. Rhind S, Rakesh J, Richardson D, Di Battista A, Lanius R. Dysregulation of hypothalamic-pituitary-adrenal axis and sympathoadrenergic system is associated with posttraumatic stress disorder in combat veterans. Biolo Psychiatry. 2017; 81(10 Suppl): S394. Dias BG. Hormonal influences on memory dimensions of post-traumatic stress disorder. Psychoneuroendocrinology. 2017; 83(Suppl):82-3. Chen C-Y, Stein M, Ursano R, Cai T, Gelernter J, Heeringa S, et al. Genome-wide association study of post traumatic stress disorder symptom domains in two cohorts of United States army soldiers. Biol Psychiatry. 2017;81(10):S91-S2. Liberzon I, Duncan L, Nievergelt C, Ressler K, Koenen K. First wave genome wide study In PTSD: genetic overlap and sex differences in heritability. Eur Neuropsychopharmacol. 2017;27(Suppl 3): S415-6. Mason O, Verwoerd M. Graph theory and networks in biology. IET Syst Biol. 2007; 1 (2): 89-119. Lesne A. Complex networks: from graph theory to biology. Lett Math Phys. 2006; 78(3): 235-62. Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA. Protein-protein interaction networks (PPI) and complex diseases. Gastroenterol Hepatol bed bench. 2014; 7(1): 17-31. Maghvan PV, Rezaei–Tavirani M, Zali H, Nikzamir A, Abdi S, Khodadoostan M, et al. Network analysis of common genes related to esophageal, gastric, and colon cancers. Gastroenterol Hepatol bed bench. 2017; 10(4): 295-302. Akbari S, Hosseini M, Rezaei Tavirani M, Rezaei Tavirani MR, Salehi SH, Alamrajabi M, et al. Common and differential genetically pathways between ulcerative colitis and colon adenocarcinoma. Gastroenterol Hepatol bed bench. 2017; 10(Suppl 1): S93-101 Safariâ€Alighiarloo N, Taghizadeh M, Tabatabaei SM, Shahsavari S, Namaki S, Khodakarim S, et al. Identification of new key genes for type 1 diabetes through construction and analysis of protein–protein interaction networks based on blood and pancreatic islet transcriptomes. J diabetes. 2017; 9(8): 764-77. 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: e2775. Zali H, Rezaei Tavirani M. Meningioma protein-protein interaction network. Arch Iran Med. 2014; 17(4): 262-72. Abbaszadeh HA, Peyvandi AA, Sadeghi Y, Safaei A, Zamanian-Azodi M, Khoramgah MS, et al. Er: YAG laser and cyclosporin A effect on cell cycle regulation of human gingival fibroblast cells. J lasers Med Sci. 2017; 8(3): 143-9. Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati Rad S, Hasanzadeh H, Rezaei Tavirani M, Seyyedi SS. Protein-protein interaction network could reveal the relationship between the breast and colon cancer. Gastroenterol Hepatol bed bench. 2015; 8(3): 215-24. Rezaei-Tavirani M, Zamanian-Azodi M, Rajabi S, Masoudi Nejad A, Rostami Nejad M, Rahmatirad S. Protein clustering and interactome analysis in parkinson and Alzheimer's diseases. Arch Iran Med. 2016; 19(2): 101-9 . Rezaei Tavirani M, Okhovatian F, Zamanian-Azodi M, Rezaei Tavirani M. Duchenne muscular dystrophy (DMD) protein-protein interaction mapping. Iran J child neurol. 2017; 11(4): 7-14. Karbalaei R, Piran M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Heidari MH. A systems biology analysis protein-protein interaction of NASH and IBD based on comprehensive gene information. Gastroenterol Hepatol bed bench. 2017; 10(3): 194-201. Su J, Yoon B-J, Dougherty ER. Identification of diagnostic subnetwork markers for cancer in human protein-protein interaction network. BMC bioinformatics. 2010;11(Suppl 6): S8. Feng J, He W, Song Y, Wang Y, Simpson RJ, Zhang X, et al. Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer. PLoS One. 2014; 9(5): e96671. Safaei A, Oskouie AA, Mohebbi SR, Rezaei-Tavirani M, Mahboubi M, Peyvandi M, et al. Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases. Gastroenterol Hepatol bed bench. 2016; 9(3): 158-73. Zamanian-Azodi M, Peyvandi H, Rostami-Nejad M, Safaei A, Rostami K, Vafaee R, et al. Protein-protein interaction network of celiac disease. Gastroenterol Hepatol bed bench. 2016; 9(4): 268-77. Khayer N, Zamanian-Azodi M, Mansouri V, Ghassemi-Broumand M, Rezaei-Tavirani M, Heidari MH, et al. Oral squamous cell cancer protein-protein interaction network interpretation in comparison to esophageal adenocarcinoma. Gastroenterol Hepatol bed bench. 2017; 10(2): 118-24. Doecke JD, Laws SM, Faux NG, Wilson W, Burnham SC, Lam C-P, et al. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch neurol. 2012; 69(10): 1318-25. Paczesny S, Krijanovski OI, Braun TM, Choi SW, Clouthier SG, Kuick R, et al. A biomarker panel for acute graft-versus-host disease. Blood. 2009; 113(2): 273-8. Younossi ZM, Jarrar M, Nugent C, Randhawa M, Afendy M, Stepanova M, et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH). Obes Surg. 2008; 18(11): 1430-7. Meyerhoff J, Oleshansky M, Mougey E. Psychologic stress increases plasma levels of prolactin, cortisol, and POMC-derived peptides in man. Psychosom Med. 1988; 50(3): 295-303. Dell'Osso L, Carmassi C, Del Debbio A, Dell'Osso MC, Bianchi C, da Pozzo E, et al. Brain-derived neurotrophic factor plasma levels in patients suffering from post-traumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(5): 899-902. Segman R, Shefi N, Goltser-Dubner T, Friedman N, Kaminski N, Shalev A. Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Mol psychiatry. 2005; 10(5): 500-13. Vukojevic V, Kolassa I-T, Fastenrath M, Gschwind L, Spalek K, Milnik A, et al. Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors. J Neurosci. 2014; 34(31):10274-84. Asalgoo S, Jahromi G, Meftahi G, Sahraei H. Posttraumatic stress disorder (PTSD): Mechanisms and possible treatments. Neurophysiol. 2015; 47(6): 482-9. Gill J, Vythilingam M, Page GG. Low cortisol, high DHEA, and high levels of stimulated TNFâ€Î±, and ILâ€6 in women with PTSD. J Trauma Stress. 2008; 21(6): 530-9. Ionescu IA, Dine J, Yen Y-C, Buell DR, Herrmann L, Holsboer F, et al. Intranasally administered neuropeptide S (NPS) exerts anxiolytic effects following internalization into NPS receptor-expressing neurons. Neuropsychopharmacol. 2012; 37(6): 1323-37. Sullivan GM, Ogden RT, Huang Yy, Oquendo MA, Mann JJ, Parsey RV. Higher in vivo serotonin-1a binding in posttrumatic stress disorder: a PET study with [11C) WAY-100635. Depress Anxiety. 2013; 30(3): 197-206. Cohen H, Liu T, Kozlovsky N, Kaplan Z, Zohar J, Mathé AA. The neuropeptide Y (NPY)-ergic system is associated with behavioral resilience to stress exposure in an animal model of post-traumatic stress disorder. Neuropsychopharmacol. 2012; 37(2): 350-63. Mehta D, Binder EB. Gene× environment vulnerability factors for PTSD: The HPA-axis. Neuropharmacol. 2012; 62(2): 654-62. Lindberg J. Exploring brain gene expression i animal models of behaviour. Acta Universitatis Upsaliensis; 2007. Rousseau K, Kauser S, Pritchard LE, Warhurst A, Oliver RL, Slominski A, et al. Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis. FASEB J. 2007; 21(8): 1844-56. Couëtil L, Paradis MR, Knoll J. Plasma adrenocorticotropin concentration in healthy horses and in horses with clinical signs of hyperadrenocorticism. J Vet Intern Med. 1996; 10(1): 1-6. Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity. Nutrition. 2007; 23(11): 887-94. Elenkov IJ, Chrousos GP. Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease. Trends Endocrinol Metab. 1999; 10(9): 359-68. Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci. 1995; 15(3): 1768-77. Vasterling JJ, Duke LM, Brailey K, Constans JI, Allain Jr AN, Sutker PB. Attention, learning, and memory performances and intellectual resources in Vietnam veterans: PTSD and no disorder comparisons. Neuropsychology. 2002; 16(1): 5-14. Dragunow M, Faull R. The use of c-fos as a metabolic marker in neuronal pathway tracing. J Neurosci Methods. 1989; 29(3): 261-5. Kung J-C, Chen T-C, Shyu B-C, Hsiao S, Huang ACW. Anxiety-and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder. J Biomed Sci. 2010; 17(1): 29. Oakley RH, Cidlowski JA. The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol. 2013; 132(5): 1033-44. Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, et al. International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev. 2006; 58(4): 782-97. Passos IC, Vasconcelos-Moreno MP, Costa LG, Kunz M, Brietzke E, Quevedo J, et al. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry. 2015; 2(11): 1002-12. Rodriguez FD, Covenas R. Targeting NPY, CRF/UCNs and NPS neuropeptide systems to treat Alcohol Use Disorder (AUD). Curr Med Chem. 2017; 24(23): 2528-58. Rasmusson AM, Hauger RL, Morgan CA, Bremner JD, Charney DS, Southwick SM. Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD. Biol psychiatry. 2000; 47(6): 526-39. Enman NM, Sabban EL, McGonigle P, Van Bockstaele EJ. Targeting the neuropeptide Y system in stress-related psychiatric disorders. Neurobiol Stress. 2015; 1: 33-43. Davis LL, Suris A, Lambert MT, Heimberg C, Petty F. Post-traumatic stress disorder and serotonin: new directions for research and treatment. J Psychiatry Neurosci. 1997; 22(5): 318-26. Martini C, Da Pozzo E, Carmassi C, Cuboni S, Trincavelli ML, Massimetti G, et al. Cyclic adenosine monophosphate responsive element binding protein in post-traumatic stress disorder. World J Biol Psychiatry. 2013; 14(5): 396-402. Fusco S, Ripoli C, Podda MV, Ranieri SC, Leone L, Toietta G, et al. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction. Proc Natl Acad Sci USA. 2012; 109(2): 621-6. Mellman TA, Ramsay RE, Fitzgerald SG. Divergence of PTSD and narcolepsy associated with military trauma. J Anxiety Disord. 1991; 5(3): 267-72.

Published

2018-05-29

How to Cite

Rezaei Tavirani, M., Okhovatian, F., Rostami-Nejad, M., & Rezaei Tavirani, S. (2018). Protein-Protein Interaction Network Analysis Revealed a New Prospective of Posttraumatic Stress Disorder: . Galen Medical Journal, 7, e1137. https://doi.org/10.31661/gmj.v7i.1137

Issue

Section

Original Article