title: Gene expression profiling identifies candidate biomarkers for active and latent tuberculosis.
abstract: BACKGROUND
  Tuberculosis (TB) is a serious infectious disease in that 90% of those latently infected with Mycobacterium tuberculosis present no symptoms, but possess a 10% lifetime chance of developing active TB. To prevent the spread of the disease, early diagnosis is crucial. However, current methods of detection require improvement in sensitivity, efficiency or specificity. In the present study, we conducted a microarray experiment, comparing the gene expression profiles in the peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population.
  
  
  RESULTS
  Bioinformatics analysis revealed that most of the differentially expressed genes belonged to immune responses, inflammation pathways, and cell cycle control. Subsequent RT-PCR validation identified four differentially expressed genes, NEMF, ASUN, DHX29, and PTPRC, as potential biomarkers for the detection of active and latent TB infections. Receiver operating characteristic analysis showed that the expression level of PTPRC may discriminate active TB patients from healthy individuals, while ASUN could differentiate between the latent state of TB infection and healthy condidtion. In contrast, DHX29 may be used to identify latently infected individuals among active TB patients or healthy individuals. To test the concept of using these biomarkers as diagnostic support, we constructed classification models using these candidate biomarkers and found the Naïve Bayes-based model built with ASUN, DHX29, and PTPRC to yield the best performance.
  
  
  CONCLUSIONS
  Our study demonstrated that gene expression profiles in the blood can be used to identify not only active TB patients, but also to differentiate latently infected patients from their healthy counterparts. Validation of the constructed computational model in a larger sample size would confirm the reliability of the biomarkers and facilitate the development of a cost-effective and sensitive molecular diagnostic platform for TB.
authors.affiliation: Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan. swl@mail.tygh.gov.tw.|Department of Life Sciences, National Central University, Taoyuan, Taiwan. swl@mail.tygh.gov.tw.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan. lshwu@hotmail.com.
authors.forename: Lawrence Shih-Hsin
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan. koko5696@gmail.com.
authors.forename: Guan-Mau
authors.initials: GM
authors.lastname: Huang
authors.affiliation: Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan. kaiyao.tw@gmail.com.
authors.forename: Kai-Yao
authors.initials: KY
authors.lastname: Huang
authors.affiliation: Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan. francis@saturn.yzu.edu.tw.|Innovation Center for Big Data and Digital Convergence, Yuan Ze University, Taoyuan, Taiwan. francis@saturn.yzu.edu.tw.
authors.forename: Tzong-Yi
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan. julweng@saturn.yzu.edu.tw.|Innovation Center for Big Data and Digital Convergence, Yuan Ze University, Taoyuan, Taiwan. julweng@saturn.yzu.edu.tw.
authors.forename: Julia Tzu-Ya
authors.initials: JT
authors.lastname: Weng
mesh_terms: D001499:Bayes Theorem; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000235:genetics / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D012372:ROC Curve; D015203:Reproducibility of Results; D059467:Transcriptome; D014376:Tuberculosis / Q000175:diagnosis* / Q000235:genetics / Q000382:microbiology
chemical_list: D015415:Biomarkers
references.citation: Oncogene. 2005 Dec 15;24(56):8229-39
references.pmid: 16103875
references.citation: Lancet Infect Dis. 2013 May;13(5):436-48
references.pmid: 23531392
references.citation: Sci Rep. 2012;2:878
references.pmid: 23170199
references.citation: BMC Pulm Med. 2009 May 16;9:21
references.pmid: 19445695
references.citation: Nature. 2010 Aug 19;466(7309):973-7
references.pmid: 20725040
references.citation: BMC Genomics. 2013 Feb 01;14:74
references.pmid: 23375113
references.citation: Nucleic Acids Res. 2013 Jul;41(Web Server issue):W77-83
references.pmid: 23703215
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: PLoS One. 2014 Feb 18;9(2):e88572
references.pmid: 24558401
references.citation: Annu Rev Immunol. 2003;21:107-37
references.pmid: 12414720
references.citation: BMC Infect Dis. 2010 Aug 18;10 :243
references.pmid: 20718957
references.citation: Clin Dev Immunol. 2011;2011:814943
references.pmid: 21234341
references.citation: Lancet. 2011 Jul 2;378(9785):57-72
references.pmid: 21420161
references.citation: Antimicrob Agents Chemother. 2003 Mar;47(3):833-6
references.pmid: 12604509
references.citation: Curr Opin Infect Dis. 2008 Jun;21(3):279-86
references.pmid: 18448973
references.citation: Curr Opin Immunol. 2000 Aug;12(4):432-6
references.pmid: 10899019
references.citation: Lancet Infect Dis. 2013 Apr;13(4):362-72
references.pmid: 23531389
references.citation: Clin Nutr. 2010 Aug;29(4):512-8
references.pmid: 20153570
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: Mol Biol Cell. 2009 Jun;20(11):2709-21
references.pmid: 19357193
references.citation: PLoS One. 2010 Jun 28;5(6):e11319
references.pmid: 20596522
references.citation: PLoS One. 2013;8(1):e54564
references.pmid: 23358528
references.citation: Diagn Microbiol Infect Dis. 2012 Jan;72(1):68-78
references.pmid: 22085772
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 13;109 (46):E3168-76
references.pmid: 23093667
references.citation: Clin Infect Dis. 2011 Apr 15;52(8):1031-7
references.pmid: 21460320
references.citation: J Clin Endocrinol Metab. 2002 Feb;87(2):758-63
references.pmid: 11836317
references.citation: Bioinformatics. 2011 Jun 15;27(12):1739-40
references.pmid: 21546393
references.citation: PLoS One. 2011;6(10):e26363
references.pmid: 22022605
references.citation: BMC Infect Dis. 2005 Apr 27;5:29
references.pmid: 15857515
references.citation: J Immunol. 2006 Mar 15;176(6):3707-16
references.pmid: 16517739
references.citation: Immunology. 2004 Oct;113(2):153-62
references.pmid: 15379975
references.citation: Indian J Med Microbiol. 2005 Jul;23(3):151-8
references.pmid: 16100419
references.citation: Am J Infect Control. 1998 Aug;26(4):453-64
references.pmid: 9721404
references.citation: Eur J Immunol. 2012 Nov;42(11):2844-50
references.pmid: 22821397
references.citation: PLoS One. 2011;6(8):e24290
references.pmid: 21904626
references.citation: Cell Host Microbe. 2012 Oct 18;12(4):470-83
references.pmid: 23084916
references.citation: BMC Infect Dis. 2013 Jan 28;13:45
references.pmid: 23356448
references.citation: J Mol Med (Berl). 2007 Jun;85(6):613-21
references.pmid: 17318616
references.citation: J Immunol. 2007 Aug 15;179(4):2532-41
references.pmid: 17675515
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15
references.pmid: 23203871
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8
references.pmid: 15980575
references.citation: Cell Immunol. 2010;260(2):128-36
references.pmid: 19919859
references.citation: Nat Rev Immunol. 2013 Sep;13(9):679-92
references.pmid: 23954936
references.citation: Clin Dev Immunol. 2011;2011:192630
references.pmid: 21197423
references.citation: Philos Trans R Soc Lond B Biol Sci. 2011 Oct 12;366(1579):2782-9
references.pmid: 21893541
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22217-22
references.pmid: 20018725
references.citation: Science. 2010 May 14;328(5980):856-61
references.pmid: 20466923
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: PLoS Pathog. 2011 Jun;7(6):e1002093
references.pmid: 21731490
references.citation: J Immunol. 2002 Oct 1;169(7):3480-4
references.pmid: 12244136
references.citation: Endocr Res. 2003 Aug;29(3):257-64
references.pmid: 14535627
references.citation: PLoS Biol. 2008 Jul 22;6(7):e184
references.pmid: 18651794
references.citation: J Immunol. 2007 Mar 15;178(6):3688-94
references.pmid: 17339466
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8
references.pmid: 21045058
references.citation: PLoS One. 2010 Aug 24;5(8):e12365
references.pmid: 20811496
references.citation: J Exp Med. 2008 Nov 24;205(12 ):2791-801
references.pmid: 18955568