Transcriptomic Discovery and Regulatory Network Prediction in Childhood Infectious Diarrhea: Cross-Cohort Assessment of Whole-Blood Pathway Concordance

Background: Whole-blood transcriptomics can characterize systemic responses to childhood infectious diarrhea, but exploratory regulatory predictions and candidate genes require independent assessment. Methods: We first reanalyzed pediatric whole-blood RNA sequencing data (GSE69529) using differential expression, functional enrichment, protein-association and miRNA networks, promoter sequence motifs, and inferred transcription factor activity. We subsequently compared discovery-stage pathway patterns with the independently published whole-blood microarray study GSE276395 (278 profiles). Results: In the discovery analysis, 7050 of 15,740 analyzed genes had adjusted p < 0.05. Enrichment implicated immune signaling, RNA metabolism, cell-cycle control, intracellular organization, apoptosis, trafficking, and metabolism. The regulatory predictions did not yield motifs or transcription factors meeting corrected significance thresholds. The external publication described partly concordant innate-immune, neutrophil-centered, and immunometabolic responses, but the compared 12-gene candidate lists had no exact overlap. The cohorts differed in age, etiology, assay platform, and inclusion of noninfectious inflammatory disease. No harmonized raw data meta-analysis, leukocyte deconvolution in the present reanalysis, or experimental validation was performed. Conclusions: The data support a hypothesis of shared, nonspecific whole-blood inflammatory and metabolic programs; individual candidate genes and inferred regulatory mechanisms remain unvalidated.