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Table 1 Information sources for the knowledge dataset used in this study.

From: Whole genome identification of Mycobacterium tuberculosisvaccine candidates by comprehensive data mining and bioinformatic analyses

Category   Reference Experimental model/method
(I) Literature-derived evidences:
Macrophages Growth/Survival Sassetti et al., 2003 Genes essential for growth (in strains H37Rv & BCG) (TraSH, microarray)
   Rengarajan et al., 2005 Genes necessary for survival in macrophages (TraSH, microarray)
   Stewart et al., 2005 Screening of mutants unable to inhibit phagosome acidification (STM, microarray analysis)
   Rosas-Magallanes et al., 2007 Screening of mutants attenuated in human macrophages (STM)
  Expression profile Monahan et al., 2001 M. bovis BCG protein expression in macrophages (human cell line), as compared to growth in culture media or conditions of heat shock (1,2-DE, proteomic analysis)
   Fisher et al., 2002 Genes induced following in vitro acid shock (microarray, RT-PCR)
   Schnappinger et al., 2003 Differential transcriptome of genes in the phagosome, in comparison to their expression in culture (microarray, RT-PCR)
   Talaat et al., 2004 Comparison of H37Rv expression profile between growth in lungs of BALB/c vs. macrophages (microarray, RT-PCR)
   Cappelli et al., 2006 Comparison of H37Rv gene expression in human macrophages vs. synthetic medium (microarray, RT-PCR)
MprAB Regulation He et al., 2006 Genes upregulated by MprA (in SDS treated culture); (microarray RT-PCR)
Hypoxia Expression profile Voskuil et al., 2003 Expression profile at low O2 and low concentrations of NO (inhibitor of aerobic respiration); dormancy regulated gene set; mostly overlaps with Sherman; microarray
   Sherman et al., 2001 H37Rv gene expression under hypoxia (from ambient to 0.2% O2 for 2 h)
   Schnappinger et al., 2003 Analysis of mutants deficient in NO synthase
Reactivation Expression profile Talaat et al., 2007 Difference in expression in BALB/c vs. broth after incubation with dexamethasone (microarray)
   Tufariello et al., 2006 Effect of rpf deletions on persistence and reactivation in mouse
Dormancy Expression profile Voskuil et al. 2003 Expression profile at low O2 and low concentrations of NO; dormancy regulated gene set; mostly overlaps with Sherman; microarray
   Voskuil et al., 2004 Transcription profile in non-proliferating conditions; genes induced under oxygen-depleted conditions (nrp-non-replicating persistence)
   Starck et al., 2004 Proteome comparison of aerobic and anerobic conditions (MTB Harlingen strain)
Lungs Expression profile Fenhalls et al., 2002 Expression of genes in human tuberculous granulomas (in situ hybridization)
   Shi et al., 2003 Transcription pattern of 6 H37Rv genes in mouse lungs (RT-PCR)
   Shi et al., 2004 Transcription pattern of H37Rv major secreted antigens in mouse lungs (RT-PCR)
   Dubnau et al., 2005 Expression of genes during infection in mouse lungs vs. medium (promoter trap)
   Rachman et al., 2006 Identification of genes expressed during pulmonary TB; transcription profile from clinical lung samples (granuloma vs. in vitro) (microarray)
   Tufariello et al., 2006 rpf gene expression in the lungs of infected mice
  Growth/Survival Lamichhane et al., 2005 Genes required for in vivo survival im mouse lungs (microarray screening of transposon mutants)
   Jain et al., 2007 Mutants tested for lung implantation in survival in guinea pigs and mouse aerosol models
Acr Co-regulation Florczyk et al. 2003 Identification of a 18-bp palindromic sequence motif
Secreted   Gomez et al., 2000 in silico identification of proteins harboring signal peptides but lacking membrane anchoring moieties.
Immunogenicity B-cell response Brusasca et al., 2001 Antibody response to 6 H37Rv RD1 proteins in guinea pigs and sera from pulmonary TB patients
   Yeremeev et al., 2003 Elicitation of B-cell response in mice immunized with rpf proteins (H37Rv)
   Weldingh et al., 2005 Seropotential of 35 proteins, tested by response with sera of TB patients
   Amor et al., 2005 Seroreactivity of MTB specific proteins previously predicted as secreted
  T-cell response Cockle et al., 2002 Immune response in cattle against 13 ORFs (RD1, RD2 and RD14 antigens).
   Vekemans et al., 2004 Profile of immune response in healthy and TB patients against a series of mycobacterial antigens
   Mustafa et al., 2006 Characterization of Th1 cell reactivity with RD1 antigens and peptides
Iron-regulated Regulation Rodriguez et al., 2002 Identification of genes induced by iron and by the iron-dependent regulator IdeR – comparison of H37Rv and ideR-mutant strains (microarray)
Vaccine Immunization/protection Mollenkopf et al., 2004 DNA vaccine candidates preselected by comparative proteomics (present in MTB, absent from BCG) evaluated for their protective potential (aerosol challenge of H37Rv, mice)
   Vipond et al., 2006 DNA vaccine candidates chosen by supporting data, such as virulence-associated, level of expression, growth in various conditions etc. (aerosol challenge of H37Rv, guinea pigs)
   Roupie et al., 2007 DNA vaccine candidates chosen from the DosR regulon (on the basis of strong T-cell responses in infected humans), evaluated for their immunogenicity potential (mice immunizations).
(II) in silico -based evidences:
Category Source of information/analyses
Cell wall Membranal and anchored Assignment of ORF products as membrane-attached, by:
   (1) Prediction of membrane-spanning regions by TMpred
   (2) Inference from annotation and/or domain analysis
Repeats   Inference from annotation and/or domain analysis
T-cell immunogenicity MHC class I and class II binders Compilation of experimental and predicted data from:
   (1) Screening of the public repository database of immune epitope data (IEDB)
   (2) Particular experimental evidences from the literature
   (3) Literature-derived predicted T-cell epitopes
   (4) Prediction of CTL epitopes by an integrative approach (NetCTL)