Comparative Study of Gene Expression Profiling Unravels Functions Associated with Pathogenesis of Dengue Infection

Author(s): Mohiuddin K. Warsi, Mohammad A. Kamal, Mohammed N. Baeshen, Mohammad A. Izhari, Ahmad Firoz, Mohammad Mobashir*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 41 , 2020

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Background: Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions.

Methods: For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours.

Results: The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages.

Conclusion: The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.

Keywords: Dengue infection, pathogenesis, gene expression, immune systems, inferred functions, biological pathways and functions.

Cattarino L, Rodriguez-Barraquer I, Imai N, Cummings DAT, Ferguson NM. Mapping global variation in dengue transmission intensity. Sci Transl Med 2020; 12(528): eaax4144.[] [PMID: 31996463]
Borchering RK, Huang AT, Mier-y-Teran-Romero L, Rojas DP, Rodriguez-Barraquer I, Katzelnick LC, et al. Impacts of Zika emergence in Latin America on endemic dengue transmission. Nature Communications 2019; 1-9.[]
Weber W, Fussenegger M. Emerging biomedical applications of synthetic biology. Nat Rev Genet 2011; 13(1): 21-35.[] [PMID: 22124480]
Halstead SB. Pathogenesis of dengue: challenges to molecular biology. Science 1988; 239(4839): 476-81.[] [PMID: 3277268]
Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. EVALUATING DIAGNOSTICS. Nat Rev Microbiol. Nature Publishing Group 2010; 8(12): S7-S16.
Sim S, Hibberd ML. Genomic approaches for understanding dengue: insights from the virus, vector, and host. Genome Biol Genome Biology 2016; 1-15.[]
Eong Ooi EGD. Dengue and Dengue Hemorrhagic Fever.Tropical Infectious Diseases. 3rd ed. New York: Saunders Elsevier 2011.
Chaturvedi U, Nagar R, Shrivastava R. Dengue and dengue haemorrhagic fever: implications of host genetics. FEMS Immunol Med Microbiol 2006; 47(2): 155-66.[] [PMID: 16831202]
Seema , Jain SK. Molecular mechanism of pathogenesis of dengue virus: Entry and fusion with target cell. Indian J Clin Biochem 2005; 20(2): 92-103.[] [PMID: 23105540]
Pierson TC, Diamond MS. The continued threat of emerging flaviviruses. Nature Microbiology 2020; 1-17.
Simon-Lorière E, Duong V, Tawfik A, et al. Increased adaptive immune responses and proper feedback regulation protect against clinical dengue. Sci Transl Med 2017; 9(405): eaal5088.[] [PMID: 28855396]
Firth C, Lipkin WI. The genomics of emerging pathogens. Annu Rev Genomics Hum Genet 2013; 14(1): 281-300.[] [PMID: 24003855]
R S. G B, D S. A primary dengue 2 epidemic with spontaneous haemorrhagic manifestations. Lancet 1993; 342: 560-1.[]
Martina BEE, Koraka P, Osterhaus ADME. Dengue virus pathogenesis: an integrated view. Clin Microbiol Rev 2009; 22(4): 564-81.[] [PMID: 19822889]
Morrison AC, Minnick SL, Rocha C, Forshey BM, Stoddard ST, Getis A, et al. Epidemiology of Dengue Virus in Iquitos, Peru 1999 to 2005: Interepidemic and Epidemic Patterns of Transmission.Tesh RB, editor PLoS Negl Trop Dis. 2005; 4: p. (5) e670.
Cordeiro MT, Silva AM, Brito CAA, et al. Characterization of a dengue patient cohort in Recife, Brazil. Am J Trop Med Hyg 2007; 77(6): 1128-34.[] [PMID: 18165535]
Ubol S, Masrinoul P, Chaijaruwanich J, Kalayanarooj S, Charoensirisuthikul T, Kasisith J. Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of dengue fever but not dengue hemorrhagic fever. J Infect Dis 2008; 197(10): 1459-67.[] [PMID: 18444802]
Sun P, García J, Comach G, Vahey MT, Wang Z, Forshey BM, et al. Sequential Waves of Gene Expression in Patients with Clinically Defined Dengue Illnesses Reveal Subtle Disease Phases and Predict Disease Severity.Farrar J, editor PLoS Negl Trop Dis. 2013; 7: p. (7) e2298.
Dalrymple NA, Mackow ER. Endothelial cells elicit immune-enhancing responses to dengue virus infection. J Virol 2012; 86(12): 6408-15.[] [PMID: 22496214]
Mackow ER. Endothelial cell dysfunction in viral hemorrhage and edema. 2014; 1-9.
Dalrymple NA, Mackow ER. Roles for endothelial cells in dengue virus infection. Adv Virol 2012; 2012(5): 840654.[] [PMID: 22952474]
Guzman MG, Gubler DJ, Izquierdo A, Martínez E, Halstead SB. Dengue infection. Nat Rev Dis Primers 2016; 2: 16055.[] [PMID: 27534439]
Nascimento EJM, Braga-Neto U, Calzavara-Silva CE, Gomes ALV, Abath FGC, Brito CAA, et al. Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome.Ng LFP, editor PLoS ONE 2009; 4(11): e7892.[]
Rothman AL. Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nat Rev Immunol 2011; 1-12.[]
OhAinle M, Balmaseda A, Macalalad AR, et al. Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity. Sci Transl Med 2011; 3(114): 114ra128.[] [PMID: 22190239]
T T.. Arboviruses of Medical Importance.Netter’s Infectious Diseases Jong E, Stevens D, Eds. 2012.
DH L.. Dengue and Dengue Hemorrhagic Fever.McGill, eds Hunter's Tropical Medicine and Emerging Infectious Diseases 9 ed A Ryan EH, Solomon D, T, editors. New York: Saunders Elsevier 2013.
Rodriguez-Barraquer I, Costa F, Nascimento EJM, et al. Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region. Science 2019; 363(6427): 607-10.[] [PMID: 30733412]
Corti D, Lanzavecchia A. Broadly neutralizing antiviral antibodies. Annu Rev Immunol 2013; 31(1): 705-42.[] [PMID: 23330954]
Quackenbush J. Microarray data normalization and transformation. Nat Genet 2002; 32(Suppl.): 496-501.[] [PMID: 12454644]
Simon R. Microarray-based expression profiling and informatics. Curr Opin Biotechnol 2008; 19(1): 26-9.[] [PMID: 18053704]
Ideker T, Thorsson V, Siegel AF, Hood LE. Testing for differentially-expressed genes by maximum-likelihood analysis of microarray data. J Comput Biol 2000; 7(6): 805-17.[] [PMID: 11382363]
Reimers M. Making Informed Choices about Microarray Data Analysis.Lewitter F, editor PLoS Comput Biol 2010; 6(5): e1000786.[]
Chen K-H, Wang K-J, Tsai M-L, Wang K-M, Adrian AM, Cheng W-C, et al. Gene selection for cancer identification: A decision tree model empowered by particle swarm optimization algorithm. BMC Bioinformatics. BMC Bioinformatics 2014; 15(1): 1-10. [Internet[]
Bild AH, Parker JS, Gustafson AM, et al. An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer. Breast Cancer Res 2009; 11(4): R55.[] [PMID: 19638211]
Salomonis N, Hanspers K, Zambon AC, et al. GenMAPP 2: new features and resources for pathway analysis. BMC Bioinformatics 2007; 8(1): 217.[] [PMID: 17588266]
Girke T. Microarray Analysis. 2011; 1-42.
Lapointe J, Li C, Higgins JP, et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004; 101(3): 811-6.[] [PMID: 14711987]
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102(43): 15545-50.[] [PMID: 16199517]
Mi H, Poudel S, Muruganujan A, Casagrande JT, Thomas PD. PANTHER version 10: expanded protein families and functions, and analysis tools. Nucleic Acids Res 2016; 44(D1): D336-42.[] [PMID: 26578592]
Kamal MA, Warsi MK, Alnajeebi A, Ali HA, Helmi N, Izhari MA, et al. Gene expression profiling and clinical relevance to understand the role of hypoxia and immune signaling genes and pathways in breast cancer. Journal of Internal Medicine: Science & Art 2020; 1-9.
Alexeyenko A, Sonnhammer ELL. Global networks of functional coupling in eukaryotes from comprehensive data integration. Genome Res 2009; 19(6): 1107-16.[] [PMID: 19246318]

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Year: 2020
Page: [5293 - 5299]
Pages: 7
DOI: 10.2174/1381612826666201106093148
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