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Publications

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 9 citations

PubMed: 35015839 DOI: 10.1093/cid/ciac010

Development and Validation of a Parsimonious Tuberculosis Gene Signature Using the digital NanoString nCounter Platform.

Clin Infect Dis 75(6):1022-1030

Authors: Vaishnavi Kaipilyawar, Yue Zhao, Xutao Wang, Noyal M Joseph, Selby Knudsen, Senbagavalli Prakash Babu, Muthuraj Muthaiah, Natasha S Hochberg, Sonali Sarkar, Charles R Horsburgh, Jerrold J Ellner, W Evan Johnson, Padmini Salgame

Affiliations

  • Department of Medicine, Center for Emerging Pathogens, Rutgers-New Jersey Medical School, Newark, New Jersey, USA.
  • Department of Medicine, Division of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
  • Boston Medical Center, Boston, Massachusetts, USA.
  • Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
  • Department of Microbiology, State TB Training and Demonstration Center, Government Hospital for Chest Disease, Gorimedu, Puducherry, India.
  • Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
  • Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Bioinformatics Program, Boston University, Boston, Massachusetts, USA.

Abstract

BACKGROUND

Blood-based biomarkers for diagnosing active tuberculosis (TB), monitoring treatment response, and predicting risk of progression to TB disease have been reported. However, validation of the biomarkers across multiple independent cohorts is scarce. A robust platform to validate TB biomarkers in different populations with clinical end points is essential to the development of a point-of-care clinical test. NanoString nCounter technology is an amplification-free digital detection platform that directly measures mRNA transcripts with high specificity. Here, we determined whether NanoString could serve as a platform for extensive validation of candidate TB biomarkers.

METHODS

The NanoString platform was used for performance evaluation of existing TB gene signatures in a cohort in which signatures were previously evaluated on an RNA-seq dataset. A NanoString codeset that probes 107 genes comprising 12 TB signatures and 6 housekeeping genes (NS-TB107) was developed and applied to total RNA derived from whole blood samples of TB patients and individuals with latent TB infection (LTBI) from South India. The TBSignatureProfiler tool was used to score samples for each signature. An ensemble of machine learning algorithms was used to derive a parsimonious biomarker.

RESULTS

Gene signatures present in NS-TB107 had statistically significant discriminative power for segregating TB from LTBI. Further analysis of the data yielded a NanoString 6-gene set (NANO6) that when tested on 10 published datasets was highly diagnostic for active TB.

CONCLUSIONS

The NanoString nCounter system provides a robust platform for validating existing TB biomarkers and deriving a parsimonious gene signature with enhanced diagnostic performance.

MeSH

Genes, Biomarkers, Tuberculosis, Communicable Diseases

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