title: Unbiased Identification of Blood-based Biomarkers for Pulmonary Tuberculosis by Modeling and Mining Molecular Interaction Networks.
abstract: Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB. We then implement a sensitive network mining method to shortlist gene candidates that are most central to the disease alterations. We then apply a series of filters that include applicability to multiple publicly available datasets as well as additional validation on independent patient samples, and identify a signature comprising 10 genes - FCGR1A, HK3, RAB13, RBBP8, IFI44L, TIMM10, BCL6, SMARCD3, CYP4F3 and SLPI, that can discriminate between TB and healthy controls as well as distinguish TB from latent tuberculosis and HIV in most cases. The signature has the potential to serve as a diagnostic marker of TB.
authors.affiliation: Department of Biochemistry, IISc, Bangalore 560012, India.
authors.forename: Awanti
authors.initials: A
authors.lastname: Sambarey
authors.affiliation: Department of Biochemistry, IISc, Bangalore 560012, India.
authors.forename: Abhinandan
authors.initials: A
authors.lastname: Devaprasad
authors.affiliation: Department of Biochemistry, IISc, Bangalore 560012, India.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Mohan
authors.affiliation: Centre for Infectious Disease Research (CIDR), IISc, Bangalore 560012, India.
authors.forename: Asma
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Centre for Infectious Disease Research (CIDR), IISc, Bangalore 560012, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Nayak
authors.affiliation: National Institute for Research in Tuberculosis, Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: St John's Research Institute, St. John's National Academy of Health Sciences, 560034 Bangalore, India.
authors.forename: George
authors.initials: G
authors.lastname: D'Souza
authors.affiliation: St John's Research Institute, St. John's National Academy of Health Sciences, 560034 Bangalore, India.
authors.forename: Anto
authors.initials: A
authors.lastname: Jesuraj
authors.affiliation: St John's Research Institute, St. John's National Academy of Health Sciences, 560034 Bangalore, India.
authors.forename: Chirag
authors.initials: C
authors.lastname: Dhar
authors.affiliation: NIH-NIRT-ICER, Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
authors.affiliation: Centre for Infectious Disease Research (CIDR), IISc, Bangalore 560012, India; Department of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, Great Maze Pond, London, UK.
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
authors.affiliation: Department of Biochemistry, IISc, Bangalore 560012, India. Electronic address: nchandra@biochem.iisc.ernet.in.
authors.forename: Nagasuma
authors.initials: N
authors.lastname: Chandra
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D016000:Cluster Analysis; D060085:Coinfection; D019295:Computational Biology / Q000379:methods; D057225:Data Mining / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009169:Mycobacterium tuberculosis; D011379:Prognosis; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D015398:Signal Transduction; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Biomarkers; Computational medicine; Diagnostics; Network biology; Tuberculosis