Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

EMBO Mol Med. 2019 Oct;11(10):e10431. doi: 10.15252/emmm.201910431. Epub 2019 Aug 30.

Abstract

Misdiagnosis of enteric fever is a major global health problem, resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying a machine learning algorithm to host gene expression profiles, we identified a diagnostic signature, which could distinguish culture-confirmed enteric fever cases from other febrile illnesses (area under receiver operating characteristic curve > 95%). Applying this signature to a culture-negative suspected enteric fever cohort in Nepal identified a further 12.6% as likely true cases. Our analysis highlights the power of data-driven approaches to identify host response patterns for the diagnosis of febrile illnesses. Expression signatures were validated using qPCR, highlighting their utility as PCR-based diagnostics for use in endemic settings.

Keywords: biomarker; enteric fever; machine learning; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Diagnosis, Differential
  • Gene Expression Profiling / methods*
  • Humans
  • Machine Learning
  • Molecular Diagnostic Techniques / methods*
  • Nepal
  • Polymerase Chain Reaction / methods*
  • ROC Curve
  • Typhoid Fever / diagnosis*
  • Typhoid Fever / pathology*

Associated data

  • GEO/GSE113867
  • GEO/GSE19491
  • GEO/GSE25001
  • GEO/GSE34404
  • GEO/GSE37250
  • GEO/GSE51808
  • GEO/GSE28991
  • GEO/GSE64338
  • GEO/GSE28405