Machine learning based refined differential gene expression analysis of pediatric sepsis

Abbas, Mostafa M.; EL-Manzalawy, Yasser

doi:10.1186/s12920-020-00771-4

Cited by 44 publications

(18 citation statements)

References 40 publications

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“…As in our rat model, recent studies agreed on a modification of the gene expression profile during sepsis in the young. The DNA Damage Inducible Transcript 4 ( Ddit4 ), a gene associated with higher risks of mortality, has notably been identified as overexpressed in the young with septic shock [ 49 , 50 , 51 ]. Animal septic shock models have been largely used over the past decades to better understand pathophysiological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Dupas

Persello

Blangy-Letheule

et al. 2022

IJMS

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The young population, which is particularly at risk of sepsis, is, paradoxically, rarely studied. Acute stimulation of O-GlcNAcylation, a post-translational modification involved in metabolic regulation, cell survival and stress response, is beneficial in young rats with sepsis. Considering that sepsis impacts the gene expression profile and that O-GlcNAcylation is a regulator of transcription, the aims of this study are to (i) unveil beneficial mechanisms of O-GlcNAcylation and (ii) decipher the relationship between O-GlcNAcylation and transcription during sepsis. Endotoxemic challenge was induced in 28-day-old male rats using a lipopolysaccharide injection (E. coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after, rats were assigned to no therapy or fluidotherapy (NaCl 0.9%, 10 mL.kg−1) ± NButGT (10 mg·kg−1) to stimulate O-GlcNAc levels. Cardiac O-GlcNAcylation levels were evaluated via Western blot and gene transcription using 3′ SRP analysis. Lipopolysaccharide injection favorizes inflammatory state with the overexpression of genes involved in the NF-κB, JAK/STAT and MAPK pathways. NButGT treatment increased cardiac O-GlcNAcylation levels (p < 0.05). Yet, the mRNA expression was not impacted two hours after fluidotherapy or NButGT treatment. In conclusion, O-GlcNAc stimulation-induced beneficial effects are not dependent on the gene expression profile at the early phase of sepsis.

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Section: Discussionmentioning

confidence: 99%

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Dupas

Persello

Blangy-Letheule

et al. 2022

IJMS

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“…Importantly, a recent study using two feature selection methods including Random Forest Feature Importance (RFFI) and Minimum Redundancy and Maximum Relevance (MRMR) also provided multiple differentially expressed genes and enriched pathways for pediatric sepsis. Within these, MPO was also a primary candidate ( 37 ). Using two potential target genes (MMP9 and MPO), we established a logistic regression model aiming for pediatric sepsis prediction.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Gene Targets for Pediatric Sepsis Based on Bioinformatics and Machine Learning

2021

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Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens.Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case–control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method.Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research.

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“…Omics technologies provide data on genome-wide gene expression, protein translation and metabolite production that are differentially regulated in neonatal sepsis 137 , 138 . Proteomics measures protein components released after infection or inflammation.…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

Diagnosis of neonatal sepsis: the past, present and future

et al. 2021

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Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins and acute phase reactants have been used for diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy, early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes.

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Machine learning based refined differential gene expression analysis of pediatric sepsis

Cited by 44 publications

References 40 publications

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Beneficial Effects of O-GlcNAc Stimulation in a Young Rat Model of Sepsis: Beyond Modulation of Gene Expression

Identification of Potential Diagnostic Gene Targets for Pediatric Sepsis Based on Bioinformatics and Machine Learning

Diagnosis of neonatal sepsis: the past, present and future

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