Transcriptomic signatures differentiate survival from fatal outcomes in humans infected with Ebola virus

Genome Biology

Volumn 18, Issue 1, 2017, Pages

  Liu, Xuan ^a,b   Speranza, Emily ^c   Muñoz Fontela, César ^d,e,f   Haldenby, Sam ^b   Rickett, Natasha Y ^a,b   Garcia Dorival, Isabel ^b   Fang, Yongxiang ^b   Hall, Yper ^g   Zekeng, Elsa Gayle ^a,b   Lüdtke, Anja ^d,e   Xia, Dong ^b   Kerber, Romy ^e   Krumkamp, Ralf ^e   Duraffour, Sophie ^e   Sissoko, Daouda ^h   Kenny, John ^b   Rockliffe, Nichola ^b   Williamson, E Diane ⁱ   Laws, Thomas R ⁱ   N'Faly, Magassouba ^j   Matthews, David A ^k   Günther, Stephan ^e,f   Cossins, Andrew R ^b   Sprecher, Armand ^m   Connor, John H ^c   Carroll, Miles W ^g,l   Hiscox, Julian A ^a,b   more..

^a Health Protection Research Unit In Emerging and Zoonotic Infections ^*  (United Kingdom)

^b UNIVERSITY OF LIVERPOOL   (United Kingdom)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d LEIBNIZ INSTITUTE FOR EXPERIMENTAL VIROLOGY   (Germany)

^e BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE   (Germany)

^f German Center for Infection Research (DZIF)   (Germany)

^g PUBLIC HEALTH ENGLAND   (United Kingdom)

^h BORDEAUX UNIVERSITY HOSPITAL   (France)

ⁱ DEFENCE SCIENCE AND TECHNOLOGY LABORATORY   (United Kingdom)

^j Hôpital National Donka service des Maladies infectieuses et Tropicales   (Guinea)

^k UNIVERSITY OF BRISTOL   (United Kingdom)

^l NATIONAL INSTITUTES OF HEALTH   (United States)

^m MÉDECINS SANS FRONTIÈRES   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; FIBRINOGEN; INTERFERON; MESSENGER RNA; TRANSCRIPTOME;

ACUTE PHASE RESPONSE; ALBUMIN GENE; ARTICLE; BLOOD ANALYSIS; CONTROLLED STUDY; EBOLA HEMORRHAGIC FEVER; FATALITY; FIBRINOGEN GENE; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; HUMAN; HUMAN CELL; LYMPHOCYTE SUBPOPULATION; NATURAL KILLER CELL; NONHUMAN; OUTCOME ASSESSMENT; PREDICTION; SIGNAL TRANSDUCTION; SURVIVAL RATE; TRANSCRIPTOMICS; UPREGULATION; VIRUS GENE; VIRUS LOAD; BIOLOGY; CLUSTER ANALYSIS; DISEASE RESISTANCE; EBOLAVIRUS; GENE EXPRESSION PROFILING; GENETICS; GUINEA; HOST PATHOGEN INTERACTION; IMMUNOLOGY; METABOLISM; MIXED INFECTION; PROCEDURES; RECEIVER OPERATING CHARACTERISTIC; T LYMPHOCYTE SUBPOPULATION; VIROLOGY;

CLUSTER ANALYSIS; COINFECTION; COMPUTATIONAL BIOLOGY; DISEASE RESISTANCE; EBOLAVIRUS; GENE EXPRESSION PROFILING; GUINEA; HEMORRHAGIC FEVER, EBOLA; HOST-PATHOGEN INTERACTIONS; HUMANS; INTERFERONS; KILLER CELLS, NATURAL; PATIENT OUTCOME ASSESSMENT; ROC CURVE; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS; TRANSCRIPTOME; VIRAL LOAD;

EID: 85010016513     PISSN: 14747596     EISSN: 1474760X     Source Type: Journal    
DOI: 10.1186/s13059-016-1137-3     Document Type: Article

References (50)

1. Carroll MW, Matthews DA, Hiscox JA, Elmore MJ, Pollakis G, Rambaut A, et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature. 2015;524:97-101.
2. Crowe SJ, Maenner MJ, Kuah S, Erickson BR, Coffee M, Knust B, et al. Prognostic indicators for Ebola patient survival. Emerg Infect Dis. 2016;22:217-23.
3. Uyeki TM, Mehta AK, Davey Jr RT, Liddell AM, Wolf T, Vetter P, et al. Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med. 2016;374:636-46.
4. Trad MA, Naughton W, Yeung A, Mazlin L, O'sullivan M, Gilroy N, Fisher DA, Stuart RL. Ebola virus disease: an update on current prevention and management strategies. J Clin Virol. 2017;86:5-13. doi: 10.1016/j.jcv.2016.11.005. Epub 2016 Nov 11.
5. Shah T, Greig J, van der Plas LM, Achar J, Caleo G, Squire JS, et al. Inpatient signs and symptoms and factors associated with death in children aged 5 years and younger admitted to two Ebola management centres in Sierra Leone, 2014: a retrospective cohort study. Lancet Glob Health. 2016;4:e495-501.
6. McElroy AK, Akondy RS, Davis CW, Ellebedy AH, Mehta AK, Kraft CS, et al. Human Ebola virus infection results in substantial immune activation. Proc Natl Acad Sci U S A. 2015;112:4719-24.
7. Ebihara H, Rockx B, Marzi A, Feldmann F, Haddock E, Brining D, et al. Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus. J Infect Dis. 2011;204 Suppl 3:S991-9.
8. Wauquier N, Becquart P, Padilla C, Baize S, Leroy EM. Human fatal Zaire Ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS Negl Trop Dis. 2010;4, e837.
9. Ruibal P, Oestereich L, Ludtke A, Becker-Ziaja B, Wozniak DM, Kerber R, et al. Unique human immune signature of Ebola virus disease in Guinea. Nature. 2016;533:100-4.
10. Mupere E, Kaducu OF, Yoti Z. Ebola haemorrhagic fever among hospitalised children and adolescents in northern Uganda: epidemiologic and clinical observations. Afr Health Sci. 2001;1:60-5.
11. McElroy AK, Erickson BR, Flietstra TD, Rollin PE, Nichol ST, Towner JS, et al. Biomarker correlates of survival in pediatric patients with Ebola virus disease. Emerg Infect Dis. 2014;20:1683-90.
12. McElroy AK, Erickson BR, Flietstra TD, Rollin PE, Nichol ST, Towner JS, et al. Ebola hemorrhagic Fever: novel biomarker correlates of clinical outcome. J Infect Dis. 2014;210:558-66.
13. Fitzpatrick G, Vogt F, Moi Gbabai OB, Decroo T, Keane M, De Clerck H, et al. The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Medecins Sans Frontieres Ebola Case Management Centre, Kailahun, Sierra Leone, June-October 2014. J Infect Dis. 2015;212:1752-8.
14. Sissoko D, Laouenan C, Folkesson E, M'Lebing AB, Beavogui AH, Baize S, et al. Experimental treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016;13, e1001967.
15. Deen GF, Knust B, Broutet N, Sesay FR, Formenty P, Ross C, et al. Ebola RNA persistence in semen of Ebola Virus Disease survivors - preliminary report. N Engl J Med. 2015. doi: 10.1056/NEJMoa1511410.
16. Marzi A, Feldmann F, Hanley PW, Scott DP, Gunther S, Feldmann H. Delayed disease progression in cynomolgus macaques infected with Ebola virus Makona strain. Emerg Infect Dis. 2015;21:1777-83.
17. Smither SJ, Eastaugh L, Ngugi S, O'Brien L, Phelps A, Steward J, et al. Ebola virus Makona shows reduced lethality in an immune-deficient mouse model. J Infect Dis. 2016;214 Suppl 3:S268-74.
18. Shin H, Shannon CP, Fishbane N, Ruan J, Zhou M, Balshaw R, et al. Variation in RNA-Seq transcriptome profiles of peripheral whole blood from healthy individuals with and without globin depletion. PLoS One. 2014;9, e91041.
19. Hutchinson KL, Rollin PE. Cytokine and chemokine expression in humans infected with Sudan Ebola virus. J Infect Dis. 2007;196 Suppl 2:S357-63.
20. Barrenas F, Green RR, Thomas MJ, Law GL, Proll SC, Engelmann F, et al. Next generation sequencing reveals a controlled immune response to Zaire Ebola virus challenge in cynomolgus macaques immunized with VSVΔG/EBOVgp. Clin Vaccine Immunol. 2015;22:354-6.
21. Altboum Z, Steuerman Y, David E, Barnett-Itzhaki Z, Valadarsky L, Keren-Shaul H, et al. Digital cell quantification identifies global immune cell dynamics during influenza infection. Mol Syst Biol. 2014;10:720.
22. Reed DS, Hensley LE, Geisbert JB, Jahrling PB, Geisbert TW. Depletion of peripheral blood T lymphocytes and NK cells during the course of ebola hemorrhagic Fever in cynomolgus macaques. Viral Immunol. 2004;17:390-400.
23. McElroy AK, Harmon JR, Flietstra TD, Campbell S, Mehta AK, Kraft CS, et al. Kinetic analysis of biomarkers in a cohort of US patients with Ebola virus disease. Clin Infect Dis. 2016;63:460-7.
24. Smith LM, Hensley LE, Geisbert TW, Johnson J, Stossel A, Honko A, et al. Interferon-beta therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever. J Infect Dis. 2013;208:310-8.
25. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377:849-62.
26. Geisbert TW, Young HA, Jahrling PB, Davis KJ, Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis. 2003;188:1618-29.
27. Okubo S, Miyamoto M, Takami K, Kanki M, Ono A, Nakatsu N, et al. Identification of novel liver-specific mRNAs in plasma for biomarkers of drug-induced liver injury and quantitative evaluation in rats treated with various hepatotoxic compounds. Toxicol Sci. 2013;132:21-31.
28. Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa--clinical manifestations and management. N Engl J Med. 2014;371:2054-7.
29. Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK, Colubri A, et al. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014;371:2092-100.
30. Lyon GM, Mehta AK, Varkey JB, Brantly K, Plyler L, McElroy AK, et al. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014;371:2402-9.
31. Rubins KH, Hensley LE, Wahl-Jensen V, Daddario DiCaprio KM, Young HA, Reed DS, et al. The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever. Genome Biol. 2007;8:R174.
32. Williams KJ, Qiu X, Fernando L, Jones SM, Alimonti JB. VSVDeltaG/EBOV GP-induced innate protection enhances natural killer cell activity to increase survival in a lethal mouse adapted Ebola virus infection. Viral Immunol. 2015;28:51-61.
33. Colubri A, Silver T, Fradet T, Retzepi K, Fry B, Sabeti P. Transforming clinical data into actionable prognosis models: machine-learning framework and field-deployable app to predict outcome of Ebola patients. PLoS Negl Trop Dis. 2016;10, e0004549.
34. Cox E, Borio L, Temple R. Evaluating Ebola therapies--the case for RCTs. N Engl J Med. 2014;371:2350-1.
35. Adebamowo C, Bah-Sow O, Binka F, Bruzzone R, Caplan A, Delfraissy JF, et al. Randomised controlled trials for Ebola: practical and ethical issues. Lancet. 2014;384:1423-4.
36. Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA. 2014;312:1299-300.
37. Buggert M, Tauriainen J, Yamamoto T, Frederiksen J, Ivarsson MA, Michaelsson J, et al. T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection. PLoS Pathog. 2014;10, e1004251.
38. Wahl-Jensen VM, Afanasieva TA, Seebach J, Ströher U, Feldmann H, Schnittler H-J. Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol. 2005;79:10442-50.
39. Zaas AK, Chen M, Varkey J, Veldman T, Hero 3rd AO, Lucas J, et al. Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans. Cell Host Microbe. 2009;6:207-17.
40. Garamszegi S, Yen JY, Honko AN, Geisbert JB, Rubins KH, Geisbert TW, et al. Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus. PLoS Negl Trop Dis. 2014;8, e3061.
41. Tsalik EL, Henao R, Nichols M, Burke T, Ko ER, McClain MT, et al. Host gene expression classifiers diagnose acute respiratory illness etiology. Sci Transl Med. 2016;8:322ra311.
42. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet journal. 2011;17:10-2.
43. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14:R36.
44. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9:357-9.
45. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26:139-40.
46. Meyer D, Dimitriadou E, Hornik K, Weingessel A, Leisch F, Chang CC, et al. Support Vector Machines: The Interface to libsvm in package e1071. R package version 16-7. 2015. http://CRAN.R-project.org/package=e1071.
47. Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier performance in R. Bioinformatics. 2005;21:3940-1.
48. Villadangos JA, Shortman K. Found in translation: the human equivalent of mouse CD8+ dendritic cells. J Exp Med. 2010;207:1131-4.
49. Haniffa M, Shin A, Bigley V, McGovern N, Teo P, See P, et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity. 2012;37:60-73.
50. Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669-92.