Background
Meningococcal Septic Shock (MSS) is a life-threatening condition, especially in Infants. Therefore the ability to track MSS pathogenesis during using temporal microarray data was explored. Gene Modular association analysis of Meningococcal Septic Shock time series data in infants was explored using WGCNA. 5 infants with Meningococcal Sepsis were admitted to PCC were recruited into the study. Secondary data analysis was completed on data points collected at 0, 4, 8, 12, 24, and 48 hours following admission. Machine Learning algorithms were also used to predict sepsis survival. These included Support Vector Machine (SVM), Naive Bayes, K-Nearest Neighbors (KNN), Decision Tree, Random Forest and ANN (Artificial Neural Network).
Results
WGCNA was applied to time-series transcriptome data (from the Arraygen Human 1.0 ST array platform) obtained from 5 PCC MSS cases. Log base 2 (log2) normalisation (ArrayExpress E-MEXP-3850) {Kwan, 2013 #49} was then undertaken on the gene expression data. Unsupervised hierarchical clustering was then applied with a heat map generated, indicating time points 0 and 48 hours as the most different in terms of gene expression. WGCNA was constructed using a soft threshold power of 6 based on network topology characteristics. Subsequently, 18 clusters (modules) were identified and compared to clinical parameters. From the adjacency matrix, a gene list was generated for each module which was significantly associated with clinical traits. Each gene list underwent gene enrichment analysis using g:profiler using the Fisher exact test for gene enrichment pathway analysis. The modules associated with Pediatric Logistic Organ Dysfunction (PELOD) score at 0, 24, and 48 hours showed a changing pattern of enriched pathways related to nuclear (p < 2e-08), cytoplasmic (p < 4e-05), and then extracellular gene regulation (p < 7e-17) for PELOD 0, 24 and 48 hours, respectively. The classification of survival and non-survival dataset using the proposed machine learning ANN technique achieved accuracies of 100% for both train and test data.
Conclusion
Time series transcriptomic analysis using WGCNA applied to a meningococcal septic shock dataset revealed an association between MSS clinical traits and major cellular processes activated through the study period of up-to 48 hours post admission. Using WGCNA, this study demonstrated the association of temporal clinical characteristics to changing cellular processes. Among ML algorithms, ANN generated the best accuracy in sepsis prediction. Thereby WCGNA and ML approached may provide a clinical linkage approach for precision management strategies in sepsis.