Ontology highlight
ABSTRACT: Background
Transcriptomics has been used to evaluate immune responses during malaria in diverse cohorts worldwide. However, the high heterogeneity of cohorts and poor generalization of transcriptional signatures reported in each study limit their potential clinical applications.Methods
We compiled 28 public data sets containing 1556 whole-blood or peripheral blood mononuclear cell transcriptome samples. We estimated effect sizes with Hedge's g value and the DerSimonian-Laird random-effects model for meta-analyses of uncomplicated malaria. Random forest models identified gene signatures that discriminate malaria from bacterial infections or malaria severity. Parasitological, hematological, immunological, and metabolomics data were used for validation.Results
We identified 3 gene signatures: the uncomplicated Malaria Meta-Signature, which discriminates Plasmodium falciparum malaria from uninfected controls; the Malaria or Bacteria Signature, which distinguishes malaria from sepsis and enteric fever; and the cerebral Malaria Meta-Signature, which characterizes individuals with cerebral malaria. These signatures correlate with clinical hallmark features of malaria. Blood transcription modules indicate immune regulation by glucocorticoids, whereas cell development and adhesion are associated with cerebral malaria.Conclusions
Transcriptional meta-signatures reflecting immune cell responses provide potential biomarkers for translational innovation and suggest critical roles for metabolic regulators of inflammation during malaria.
SUBMITTER: Silva NI
PROVIDER: S-EPMC11326815 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Silva Nágila Isleide NI Souza Pedro Felipe Loyola PFL Silva Bárbara Fernandes BF Fonseca Simone Gonçalves SG Gardinassi Luiz Gustavo LG
The Journal of infectious diseases 20240801 2
<h4>Background</h4>Transcriptomics has been used to evaluate immune responses during malaria in diverse cohorts worldwide. However, the high heterogeneity of cohorts and poor generalization of transcriptional signatures reported in each study limit their potential clinical applications.<h4>Methods</h4>We compiled 28 public data sets containing 1556 whole-blood or peripheral blood mononuclear cell transcriptome samples. We estimated effect sizes with Hedge's g value and the DerSimonian-Laird rand ...[more]