Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

PLoS Neglected Tropical Diseases

Volumn 10, Issue 2, 2016, Pages

  Voge, Natalia V ^a   Perera, Rushika ^a   Mahapatra, Sebabrata ^a   Gresh, Lionel ^b   Balmaseda, Angel ^c   Loroño Pino, María A ^d   Hopf Jannasch, Amber S ^e   Belisle, John T ^a   Harris, Eva ^f   Blair, Carol D ^a   Beaty, Barry J ^a  

^a Department of Environmental and Radiological Health Sciences   (United States)

^b Sustainable Sciences Institute   (Nicaragua)

^c Ministry of Health   (Nicaragua)

^d UNIVERSIDAD AUTÓNOMA DE YUCATÁN   (Mexico)

^e PURDUE UNIVERSITY   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARACHIDONIC ACID; BIOLOGICAL MARKER; COLECALCIFEROL; DOCOSAHEXAENOIC ACID; LINOLENIC ACID; PROLINE; PROTEIN;

ADOLESCENT; ADULT; AGED; ARTICLE; CHILD; CITIZEN GROUP; DENGUE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HYDROPHILIC INTERACTION CHROMATOGRAPHY; MAJOR CLINICAL STUDY; MALE; METABOLITE; METABOLOME; METABOLOMICS; OUTCOME ASSESSMENT; PRIMARY INFECTION; REPRODUCIBILITY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SECONDARY INFECTION; TANDEM MASS SPECTROMETRY; BLOOD; CHEMISTRY; DENGUE VIRUS; EVALUATION STUDY; INFANT; METABOLISM; MEXICO; MIDDLE AGED; NICARAGUA; PHYSIOLOGY; PRESCHOOL CHILD; PROCEDURES; VIROLOGY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; BIOMARKERS; CHILD; CHILD, PRESCHOOL; DENGUE; DENGUE VIRUS; FEMALE; HUMANS; INFANT; MALE; METABOLOMICS; MEXICO; MIDDLE AGED; NICARAGUA; PROTEINS; TANDEM MASS SPECTROMETRY; YOUNG ADULT;

EID: 84959275196     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0004449     Document Type: Article

References (93)

1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013Apr25;496(7446):504–7. doi: 10.1038/nature1206023563266
2. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol. 2010Dec;8(12 Suppl):S7–16. doi: 10.1038/nrmicro246021079655
3. Halstead SB, Dengue. Lancet. 2007Nov10;370(9599):1644–52. 17993365
4. Rothman AL, Ennis FA, Immunopathogenesis of dengue hemorrhagic fever. Virology. 1999Apr25;257(1):1–6. 10208914
5. Simmons CP, Farrar JJ, Nguyen v V, Wills B, Dengue. N Engl J Med. 2012Apr12;366(15):1423–32. doi: 10.1056/NEJMra111026522494122
6. Yacoub S, Wills B, Predicting outcome from dengue. BMC Med. 2014;12:147. doi: 10.1186/s12916-014-0147-925259615
7. Special programme for research and training in tropical diseases WHODengue. Guidelines for diagnosis, treatment, prevention and control. Geneva, Switzerland: TDR/World Health Organization; 2009.
8. Cheng HJ, Luo YH, Wan SW, Lin CF, Wang ST, Hung NT, et al. Correlation between serum levels of anti-endothelial cell autoantigen and anti-dengue virus nonstructural protein 1 antibodies in dengue patients. Am J Trop Med Hyg. 2015May6;92(5):989–95. doi: 10.4269/ajtmh.14-016225758647
9. Chuang YC, Wang SY, Lin YS, Chen HR, Yeh TM, Re-evaluation of the pathogenic roles of nonstructural protein 1 and its antibodies during dengue virus infection. J Biomed Sci. 2013Jun27;20.
10. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J Infect Dis. 2000Jan;181(1):2–9. 10608744
11. Libraty DH, Young PR, Pickering D, Endy TP, Kalayanarooj S, Green S, et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J Infect Dis. 2002Oct15;186(8):1165–8. 12355369
12. Bozza FA, Cruz OG, Zagne SM, Azeredo EL, Nogueira RM, Assis EF, et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infect Dis. 2008;8:86. doi: 10.1186/1471-2334-8-8618578883
13. Huy NT, Van Giang T, Thuy DH, Kikuchi M, Hien TT, Zamora J, et al. Factors associated with dengue shock syndrome: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2013;7(9):e2412. doi: 10.1371/journal.pntd.000241224086778
14. Loke H, Bethell D, Phuong CX, Day N, White N, Farrar J, et al. Susceptibility to dengue hemorrhagic fever in Vietnam: evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes. Am J Trop Med Hyg. 2002Jul;67(1):102–6. 12363051
15. Loke P, Hammond SN, Leung JM, Kim CC, Batra S, Rocha C, et al. Gene expression patterns of dengue virus-infected children from Nicaragua reveal a distinct signature of increased metabolism. PLoS Negl Trop Dis. 2010;4(6):e710. doi: 10.1371/journal.pntd.000071020559541
16. Michels M, Sumardi U, de Mast Q, Jusuf H, Puspita M, Dewi IM, et al. The predictive diagnostic value of serial daily bedside ultrasonography for severe dengue in Indonesian adults. PLoS Negl Trop Dis. 2013;7(6):e2277. doi: 10.1371/journal.pntd.000227723785539
17. Michels M, van der Ven AJ, Djamiatun K, Fijnheer R, de Groot PG, Griffioen AW, et al. Imbalance of angiopoietin-1 and angiopoetin-2 in severe dengue and relationship with thrombocytopenia, endothelial activation, and vascular stability. Am J Trop Med Hyg. 2012Nov;87(5):943–6. doi: 10.4269/ajtmh.2012.12-002022949515
18. Page AV, Liles WC, Biomarkers of endothelial activation/dysfunction in infectious diseases. Virulence. 2013Aug15;4(6):507–16. doi: 10.4161/viru.2453023669075
19. Sun P, Garcia 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. PLoS Negl Trop Dis. 2013;7(7):e2298. doi: 10.1371/journal.pntd.000229823875036
20. Vejbaesya S, Luangtrakool P, Luangtrakool K, Kalayanarooj S, Vaughn DW, Endy TP, et al. TNF and LTA gene, allele, and extended HLA haplotype associations with severe dengue virus infection in ethnic Thais. J Infect Dis. 2009May15;199(10):1442–8. doi: 10.1086/59742219392621
21. Villar-Centeno LA, Diaz-Quijano FA, Martinez-Vega RA, Biochemical alterations as markers of dengue hemorrhagic fever. Am J Trop Med Hyg. 2008Mar;78(3):370–4. 18337328
22. Brasier AR, Ju H, Garcia J, Spratt HM, Victor SS, Forshey BM, et al. A three-component biomarker panel for prediction of dengue hemorrhagic fever. Am J Trop Med Hyg. 2012Feb;86(2):341–8. doi: 10.4269/ajtmh.2012.11-046922302872
23. Lee IK, Liu JW, Yang KD, Fatal dengue hemorrhagic fever in adults: emphasizing the evolutionary pre-fatal clinical and laboratory manifestations. PLoS Negl Trop Dis. 2012;6(2):e1532. doi: 10.1371/journal.pntd.000153222363829
24. Poole-Smith BK, Gilbert A, Gonzalez AL, Beltran M, Tomashek KM, Ward BJ, et al. Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever. Am J Trop Med Hyg. 2014Dec;91(6):1218–26. doi: 10.4269/ajtmh.14-019325349378
25. Potts JA, Gibbons RV, Rothman AL, Srikiatkhachorn A, Thomas SJ, Supradish PO, et al. Prediction of dengue disease severity among pediatric Thai patients using early clinical laboratory indicators. PLoS Negl Trop Dis. 2010;4(8):e769. doi: 10.1371/journal.pntd.000076920689812
26. Silva MM, Gil LH, Marques ET, Jr.Calzavara-Silva CE, Potential biomarkers for the clinical prognosis of severe dengue. Mem Inst Oswaldo Cruz. 2013Sep;108(6):755–62. doi: 10.1590/0074-027610806201301224037198
27. Tanner L, Schreiber M, Low JG, Ong A, Tolfvenstam T, Lai YL, et al. Decision tree algorithms predict the diagnosis and outcome of dengue fever in the early phase of illness. PLoS Negl Trop Dis. 2008;2(3):e196. doi: 10.1371/journal.pntd.000019618335069
28. Lam PK, Hoai Tam DT, Dung NM, Hanh Tien NT, Thanh Kieu NT, Simmons C, et al. A prognostic model for development of profound shock among children presenting with dengue shock syndrome. PLoS One. 2015;10(5):e0126134. doi: 10.1371/journal.pone.012613425946113
29. UNICEF/WHODengue diagnostics: proceedings of an international workshop. Special Programme for Research and Training in Tropical Diseases. Geneva, Switzerland: WHO/TDR; 2004. p. 3–11, 76–9.
30. WHODengue haemorrhagic fever: diagnosis, treatment, prevention and control. Geneva: World Health Organization1997 Available from: http://www.who.int/csr/resources/publications/dengue/Denguepublication/en/.
31. Al-Mubarak R, Vander Heiden J, Broeckling CD, Balagon M, Brennan PJ, Vissa VD, Serum metabolomics reveals higher levels of polyunsaturated fatty acids in lepromatous leprosy: potential markers for susceptibility and pathogenesis. PLoS Negl Trop Dis. 2011Sep;5(9):e1303. doi: 10.1371/journal.pntd.000130321909445
32. Cui L, Lee YH, Kumar Y, Xu F, Lu K, Ooi EE, et al. Serum metabolome and lipidome changes in adult patients with primary dengue infection. PLoS Negl Trop Dis. 2013Aug;7(8):e2373. doi: 10.1371/journal.pntd.000237323967362
33. Mahapatra S, Hess AM, Johnson JL, Eisenach KD, Degroote MA, Gitta P, et al. A metabolic biosignature of early response to anti-tuberculosis treatment. BMC Infect Dis. 2014;14(1):53.
34. Pacchiarotta T, Deelder AM, Mayboroda OA, Metabolomic investigations of human infections. Bioanalysis. 2012May;4(8):919–25. doi: 10.4155/bio.12.6122533566
35. Vinayavekhin N, Homan EA, Saghatelian A, Exploring disease through metabolomics. ACS Chem Biol. 2010Jan15;5(1):91–103. doi: 10.1021/cb900271r20020774
36. Molins CR, Ashton LV, Wormser GP, Hess AM, Delorey MJ, Mahapatra S, et al. Development of a metabolic biosignature for detection of early lyme disease. Clin Infect Dis. 2015Jun15;60(12):1767–75. doi: 10.1093/cid/civ18525761869
37. Perera R, Riley C, Isaac G, Hopf-Jannasch AS, Moore RJ, Weitz KW, et al. Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS Pathog. 2012;8(3):e1002584. doi: 10.1371/journal.ppat.100258422457619
38. Greco G, Letzel T, Main interactions and influences of the chromatographic parameters in HILIC separations. J Chromatogr Sci. 2013Aug;51(7):684–93. doi: 10.1093/chromsci/bmt01523492984
39. Rojo D, Barbas C, Ruperez FJ, LC-MS metabolomics of polar compounds. Bioanalysis. 2012Jun;4(10):1235–43. doi: 10.4155/bio.12.10022651567
40. Narvaez F, Gutierrez G, Perez MA, Elizondo D, Nunez A, Balmaseda A, et al. Evaluation of the traditional and revised WHO classifications of dengue disease severity. PLoS Negl Trop Dis. 2011Nov;5(11):e1397. doi: 10.1371/journal.pntd.000139722087348
41. Gutierrez G, Gresh L, Perez MA, Elizondo D, Aviles W, Kuan G, et al. Evaluation of the diagnostic utility of the traditional and revised WHO dengue case definitions. PLoS Negl Trop Dis. 2013;7(8):e2385. doi: 10.1371/journal.pntd.000238523991237
42. Biswas HH, Ortega O, Gordon A, Standish K, Balmaseda A, Kuan G, et al. Early clinical features of dengue virus infection in Nicaraguan children: a longitudinal analysis. PLoS Negl Trop Dis. 2012;6(3):e1562. doi: 10.1371/journal.pntd.000156222413033
43. Kuan G, Gordon A, Aviles W, Ortega O, Hammond SN, Elizondo D, et al. The Nicaraguan pediatric dengue cohort study: study design, methods, use of information technology, and extension to other infectious diseases. Am J Epidemiol. 2009Jul1;170(1):120–9. doi: 10.1093/aje/kwp09219435864
44. Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011Jun;6(7):1060–83. doi: 10.1038/nprot.2011.33521720319
45. Pesek JJ, Matyska MT, Our favorite materials: Silica hydride stationary phases. J Sep Sci. 2009Dec;32(23–24):3999–4011. doi: 10.1002/jssc.20090056819937606
46. Pesek JJ, Matyska MT, Loo JA, Fischer SM, Sana TR, Analysis of hydrophilic metabolites in physiological fluids by HPLC-MS using a silica hydride-based stationary phase. J Sep Sci. 2009Jul;32(13):2200–8. doi: 10.1002/jssc.20090027019569099
47. Smith CA, O'Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, et al. METLIN—A metabolite mass spectral database. Ther Drug Monit. 2005Dec;27(6):747–51. 16404815
48. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, et al. HMDB 3.0—The human metabolome database in 2013. Nucleic Acids Res. 2013Jan;41(Database issue):D801–7. doi: 10.1093/nar/gks106523161693
49. Riley C, Gough J, He J, Jandhyala S, Kennedy B, Orcun S, et al. The proteome discovery pipeline–A data analysis pipeline for mass spectrometry-based differential proteomics discovery. The Open Proteomics J. 2010;3:8–19.
50. Patiny L, Borel A, ChemCalc: a building block for tomorrow's chemical infrastructure. J Chem Inf Model. 2013May24;53(5):1223–8. doi: 10.1021/ci300563h23480664
51. Sansone SA, Fan T, Goodacre R, Griffin JL, Hardy NW, Kaddurah-Daouk R, et al. The metabolomics standards initiative. Nat Biotechnol. 2007Aug;25(8):844–8.
52. Sumner L, Amberg A, Barrett D, Beale M, Beger R, Daykin C, et al. Proposed minimum reporting standards for chemical analysis. Metabolomics. 2007 2007/09/01;3(3):211–21. 24039616
53. Simon-Manso Y, Lowenthal MS, Kilpatrick LE, Sampson ML, Telu KH, Rudnick PA, et al. Metabolite profiling of a NIST standard reference material for human plasma (SRM 1950): GC-MS, LC-MS, NMR, and clinical laboratory analyses, libraries, and web-based resources. Anal Chem. 2013Dec17;85(24):11725–31. doi: 10.1021/ac402503m24147600
54. Adamec J, Jannasch A, Huang JJ, Hohman E, Fleet JC, Peacock M, et al. Development and optimization of an LC-MS/MS-based method for simultaneous quantification of vitamin D-2, vitamin D-3, 25-hydroxyvitamin D-2 and 25-hydroxyvitamin D-3. J Sep Sci. 2011Jan;34(1):11–20. doi: 10.1002/jssc.20100041021171171
55. Aronov PA, Hall LM, Dettmer K, Stephensen CB, Hammock BD, Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2008Jul;391(5):1917–30. doi: 10.1007/s00216-008-2095-818437365
56. Tautenhahn R, Cho K, Uritboonthai W, Zhu ZJ, Patti GJ, Siuzdak G, An accelerated workflow for untargeted metabolomics using the METLIN database. Nat Biotechnol. 2012Sep;30(9):826–8.
57. Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, et al. HMDB: the human metabolome database. Nucleic Acids Res. 2007Jan;35:D521–D6. 17202168
58. Heller S, McNaught A, Stein S, Tchekhovskoi D, Pletnev I, InChI—the worldwide chemical structure identifier standard. J Cheminformatics. 2013Jan24;5.
59. Zhang GF, Sadhukhan S, Tochtrop G, Brunengraber H, Metabolomics, pathway regulation and pathway discovery. J Biol Chem. 2011May12.
60. Whitehorn J, Simmons CP, The pathogenesis of dengue. Vaccine. 2011Sep23;29(42):7221–8. doi: 10.1016/j.vaccine.2011.07.02221781999
61. Brasier AR, Garcia J, Wiktorowicz JE, Spratt HM, Comach G, Ju H, et al. Discovery proteomics and nonparametric modeling pipeline in the development of a candidate biomarker panel for dengue hemorrhagic fever. Clin Transl Sci. 2012;5(1):8–20. doi: 10.1111/j.1752-8062.2011.00377.x22376251
62. Heaton NS, Perera R, Berger KL, Khadka S, LaCount DJ, Kuhn RJ, et al. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. P Natl Acad Sci USA. 2010Oct5;107(40):17345–50.
63. Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CKE, Walther P, et al. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe. 2009;5(4):365–75. doi: 10.1016/j.chom.2009.03.00719380115
64. Calder PC, n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr. 2006Jun;83(6):1505s–19s. 16841861
65. Holy EW, Forestier M, Richter EK, Akhmedov A, Leiber F, Camici GG, et al. Dietary alpha-linolenic acid inhibits arterial thrombus formation, tissue factor expression, and platelet activation. Arterioscler Thromb Vasc Biol. 2011Aug;31(8):1772–80. doi: 10.1161/ATVBAHA.111.22611821571683
66. Bazan NG, Molina MF, Gordon WC, Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Annu Rev Nutr. 2011Aug21;31:321–51. doi: 10.1146/annurev.nutr.012809.10463521756134
67. Das UN, Essential fatty acids. Curr Pharm Biotechno. 2006Dec;7(6):455–.
68. Loke WM, Chow AY, Sing KLM, Lee CYJ, Halliwell B, Lim ECH, et al. Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection. Virol J. 2013Oct30;10.
69. Harizi H, Corcuff JB, Gualde N, Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med. 2008Oct;14(10):461–9. doi: 10.1016/j.molmed.2008.08.00518774339
70. Khanapure SP, Garvey DS, Janero DR, Letts LG, Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem. 2007;7(3):311–40. 17305573
71. Wymann MP, Schneiter R, Lipid signalling in disease. Nat Rev Mol Cell Bio. 2008Feb;9(2):162–76.
72. Hishikawa D, Shindou H, Kobayashi S, Nakanishi H, Taguchi R, Shimizu T, Discovery essential of a lysophospholipid acyltransferase family for membrane asymmetry and diversity. P Natl Acad Sci USA. 2008Feb26;105(8):2830–5.
73. Jia SJ, Jiang DJ, Hu CP, Zhang XH, Deng HW, Li YJ, Lysophosphatidylcholine-induced elevation of asymmetric dimethylarginine level by the NADPH oxidase pathway in endothelial cells. Vasc Pharmacol. 2006Mar;44(3):143–8.
74. Murugesan G, Rani MRS, Gerber CE, Mukhopadhyay C, Ransohoff RM, Chisolm GM, et al. Lysophosphatidylcholine regulates human microvascular endothelial cell expression of chemokines. J Mol Cell Cardiol. 2003Nov;35(11):1375–84. 14596794
75. Schilling T, Eder C, Sodium dependence of lysophosphatidylcholine-induced caspase-1 activity and reactive oxygen species generation. Immunobiology. 2011Jan-Feb;216(1–2):118–25. doi: 10.1016/j.imbio.2010.06.01020655126
76. Davidsen J, Mouritsen OG, Jorgensen K, Synergistic permeability enhancing effect of lysophospholipids and fatty acids on lipid membranes. Bba-Biomembranes. 2002Aug19;1564(1):256–62. 12101020
77. Qiao J, Huang F, Naikawadi RP, Kim KS, Said T, Lum H, Lysophosphatidylcholine impairs endothelial barrier function through the G protein coupled receptor GPR4Am J Physiol Lung Cell Mol Physiol. 2006Jul;291(1):91–101.
78. Huang F, Subbaiah PV, Holian O, Zhang J, Johnson A, Gertzberg N, et al. Lysophosphatidylcholine increases endothelial permeability, role of PKCalpha and RhoA cross talk. Am J Physiol Lung Cell Mol Physiol. 2005Aug;289(2):L176–85. 15764646
79. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C, Vitamin D: modulator of the immune system. Curr Opin Pharmacol. 2010Aug;10(4):482–96. doi: 10.1016/j.coph.2010.04.00120427238
80. Møller S, Laigaard F, Olgaard K, Hemmingsen C, Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis. Int J Med Sci. 2007;4(4):190–5. 17657282
81. Nguyen HB, Eshete B, Lau KH, Sai A, Villarin M, Baylink D, Serum 1,25-dihydroxyvitamin D: an outcome prognosticator in human sepsis. PLoS One. 2013;8(5):e64348. doi: 10.1371/journal.pone.006434823741318
82. Cantorna MT, Mahon BD, Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med. 2004Dec;229(11):1136–42.
83. Donald SP, Sun XY, Hu CAA, Yu J, Mei JM, Valle D, et al. Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species. Cancer Res. 2001Mar1;61(5):1810–5. 11280728
84. Krishnan N, Dickman MB, Becker DF, Proline modulates the intracellular redox environment and protects mammalian cells against oxidative stress. Free Radical Bio Med. 2008Feb15;44(4):671–81.
85. Natarajan SK, Zhu WD, Liang XW, Zhang L, Demers AJ, Zimmerman MC, et al. Proline dehydrogenase is essential for proline protection against hydrogen peroxide-induced cell death. Free Radical Bio Med. 2012Sep1;53(5):1181–91.
86. Hammond SN, Balmaseda A, Perez L, Tellez Y, Saborio SI, Mercado JC, et al. Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua. Am J Trop Med Hyg. 2005Dec;73(6):1063–70. 16354813
87. Halstead SB, Gubler DJ, Kuno G, Epidemiology of dengue and dengue hemorrhagic fever. Wallingford (UK): CAB International; 1997.
88. Yu ZH, Zhai GJ, Singmann P, He Y, Xu T, Prehn C, et al. Human serum metabolic profiles are age dependent. Aging Cell. 2012Dec;11(6):960–7. doi: 10.1111/j.1474-9726.2012.00865.x22834969
89. Halstead SB, Dengue: the syndromic basis to pathogenesis research. Inutility of the 2009 WHO case definition. Am J Trop Med Hyg. 2013Feb;88(2):212–5. doi: 10.4269/ajtmh.12-019723390220
90. Poovorawan Y, Hutagalung Y, Chongsrisawat V, Boudville I, Bock HL, Dengue virus infection: a major cause of acute hepatic failure in Thai children. Ann Trop Paediatr. 2006Mar;26(1):17–23. 16494700
91. Samanta J, Sharma V, Dengue and its effects on liver. World J Clin Cases. 2015;3(2):125–31. doi: 10.12998/wjcc.v3.i2.12525685758
92. Abbatiello SE, Mani DR, Schilling B, Maclean B, Zimmerman LJ, Feng X, et al. Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS). Mol Cell Proteomics. 2013Sep;12(9):2623–39. doi: 10.1074/mcp.M112.02707823689285
93. van der Laan MJ, Polley EC, Hubbard AE, Super learner. Stat Appl Genet Mol. 2007Oct2;6.