Fig 1.
A PRISMA flow diagram of a systematic database search.
The selection process of eligible microarray datasets for meta-analysis of the shared transcriptomic signatures between Sickle cell disease patients, according to Prisma 2009 flow diagram.
Table 1.
Characteristics of included individual microarray dataset.
Table 2.
MetaQC quantitative quality control measures for gene expression data.
Fig 2.
Workflow of microarray meta-analysis integrating GWAS data.
A flow diagram depicting the process involved in the meta-analysis of the selected microarray datasets with integration of GWAS data.
Table 3.
Top 20 shared DEGs identified in the meta-analysis ranked by average Log2FC.
Fig 3.
Network-based meta-analysis of hub genes.
A: Protein interaction network analysis indicates a central role for SKP1, NAPA, EPB42, and ARPC5 in SCD anemia. All 335 genes served as input for the STRING database with the high confidence interaction score 0.7, and a network was built by means of Cytoscape. The network topology was analyzed by the Cytoscape NetworkAnalyzer tool, and then network topology measures such as the degree (represented by the node size scale), betweenness (represented by police size scale), closeness centrality, and clustering coefficient were calculated. B and C: The top-ranked subnetwork identified by the OH-PIN algorithm (threshold: 2, overlapping score 0.5) using CytoCluster (a Cytoscape plugin).
Fig 4.
Transcriptional regulatory subnetwork based on microarray meta-analysis.
Regulatory network analysis was performed using RNEA R/package to determine the regulation complexes upstream of DEGs identified in the meta-analysis. Genes carrying in their promoter, a significant regulatory SNPs are marked by a yellow star. Each node represents a DEG or enriched transcription factor, depending on their shapes. The node size indicate greater significance of the enrichment. The edges reflect the relationships between the nodes.
Fig 5.
Over-representation of pathways and GO categories in biological networks identified by the meta-analysis.
Network representation of an enriched pathway integrating biological processes on the DEG list according to the ClueGO Cytoscape plugin. Hypergeometric (right-handed) enrichment distribution tests were conducted with a p value significance level of ≤0.05, followed by the Bonferroni adjustment for the terms, and thus leading term groups were selected based on the highest significance. Each node represents a biological process. The edges reflect the relationships between the terms based on the similarity of their associated genes. The node size and deeper color indicate greater significance of the enrichment.
Fig 6.
Downregulated and upregulated DEGs involved in apoptosis pathways.
The inner ring is a bar plot where the height of the bar indicates the significance of the term (−log10 adjusted p value), and color corresponds to the z-score. The outer ring displays scatterplots of the expression levels (log2FC) for the genes in each term.