title: Identification of a 251 gene expression signature that can accurately detect M. tuberculosis in patients with and without HIV co-infection.
abstract: BACKGROUND
  Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV.
  
  
  METHODS
  We analyzed global gene expression data from peripheral blood mononuclear cell (PBMC) samples of patients that were either mono-infected with HIV or co-infected with HIV/TB and used support vector machines to identify a gene signature that can distinguish between the two classes. We then validated our results using publically available gene expression data from patients mono-infected with TB.
  
  
  RESULTS
  Our analysis successfully identified a 251-gene signature that accurately distinguishes patients co-infected with HIV/TB from those infected with HIV only, with an overall accuracy of 81.4% (sensitivity = 76.2%, specificity = 86.4%). Furthermore, we show that our 251-gene signature can also accurately distinguish patients with active TB in the absence of an HIV infection from both patients with a latent TB infection and healthy controls (88.9-94.7% accuracy; 69.2-90% sensitivity and 90.3-100% specificity). We also demonstrate that the expression levels of the 251-gene signature diminish as a correlate of the length of TB treatment.
  
  
  CONCLUSIONS
  A 251-gene signature is described to (a) detect TB in the presence or absence of an HIV co-infection, and (b) assess response to treatment following anti-TB therapy.
authors.affiliation: Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Noor
authors.initials: N
authors.lastname: Dawany
authors.affiliation: Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
authors.affiliation: Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Kossenkov
authors.affiliation: Genomics Facility, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Celia
authors.initials: C
authors.lastname: Chang
authors.affiliation: Clinical HIV Research Unit, Department of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.affiliation: Clinical HIV Research Unit, Department of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.affiliation: Department of Molecular Medicine and Hematology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.affiliation: Clinical HIV Research Unit, Department of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Ian
authors.initials: I
authors.lastname: Sanne
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Livio
authors.initials: L
authors.lastname: Azzoni
authors.affiliation: HIV-1 Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000328:Adult; D060085:Coinfection / Q000382:microbiology* / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D012680:Sensitivity and Specificity; D013019:South Africa; D060388:Support Vector Machine; D059467:Transcriptome / Q000235:genetics*; D014376:Tuberculosis / Q000175:diagnosis*