Host Blood Gene Signatures Can Detect the Progression to Severe and Cerebral Malaria.

TitleHost Blood Gene Signatures Can Detect the Progression to Severe and Cerebral Malaria.
Publication TypeJournal Article
Year of Publication2021
AuthorsOmar M, Marchionni L, Häcker G, Badr MTarek
JournalFront Cell Infect Microbiol
Volume11
Pagination743616
Date Published2021
ISSN2235-2988
KeywordsCohort Studies, Humans, Malaria, Cerebral, Malaria, Falciparum, Reproducibility of Results, Severity of Illness Index
Abstract

Malaria is a major international public health problem that affects millions of patients worldwide especially in sub-Saharan Africa. Although many tests have been developed to diagnose malaria infections, we still lack reliable diagnostic biomarkers for the identification of disease severity, especially in endemic areas where the diagnosis of cerebral malaria is very difficult and requires the exclusion of all other possible causes. Previous host and pathogen transcriptomic studies have not yielded homogenous results that can be harnessed into a reliable diagnostic tool. Here we utilized a multi-cohort analysis approach using machine-learning algorithms to identify blood gene signatures that can distinguish severe and cerebral malaria from moderate and non-cerebral cases. Using a Regularized Random Forest model, we identified 28-gene and 32-gene signatures that can reliably distinguish severe and cerebral malaria, respectively. We tested the specificity of both signatures against other common infectious diseases to ensure the signatures reliability and suitability as diagnostic markers. The severe and cerebral malaria gene-signatures were further integrated through k-top scoring pairs classifiers into ten and nine gene pairs that could distinguish severe and cerebral malaria, respectively. These signatures have various implications that can be utilized as blood diagnostic tools for malaria severity in endemic countries.

DOI10.3389/fcimb.2021.743616
Alternate JournalFront Cell Infect Microbiol
PubMed ID34746025
PubMed Central IDPMC8569259
Related Faculty: 
Luigi Marchionni, M.D., Ph.D.

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