Figure 4.
Physical and functional interaction network of upregulated proteins in the BM microenvironment of patients with AML. (A) STRING 11.0 (Search Tool for the Retrieval of Interacting Genes) was used to visualize the predicted PPIs for the upregulated proteins identified by SOMAscan assay in the AML BM microenvironment compared with healthy controls (https://string-db.org/). Network nodes represent proteins and the lines reflect physical and/or functional interactions of proteins. Empty nodes represent the proteins of unknown three-dimensional structure, and filled nodes represent the proteins with some three-dimensional structure known or predicted. Different colored lines between the proteins represent the various types of interaction evidence in STRING (databases, experiments, neighborhood, gene fusion, cooccurrence, text mining, coexpression, and homology). (B) Upregulated proteins were subjected to enrichment analyses for KEGG and Reactome pathways as well as GO annotation for “Molecular Function” terms using STRING 11.0 tool. Graph indicates the top 29 significantly enriched GO-Molecular Function terms ranked based on -Log10(FDR) ≥3. For all other analysis, FDR ≤0.05 was used as the threshold value, and the number of proteins enriched in each pathway was ≥2. The full list of enriched pathways and terms with associated FDRs is given in supplemental Table 9.

Physical and functional interaction network of upregulated proteins in the BM microenvironment of patients with AML. (A) STRING 11.0 (Search Tool for the Retrieval of Interacting Genes) was used to visualize the predicted PPIs for the upregulated proteins identified by SOMAscan assay in the AML BM microenvironment compared with healthy controls (https://string-db.org/). Network nodes represent proteins and the lines reflect physical and/or functional interactions of proteins. Empty nodes represent the proteins of unknown three-dimensional structure, and filled nodes represent the proteins with some three-dimensional structure known or predicted. Different colored lines between the proteins represent the various types of interaction evidence in STRING (databases, experiments, neighborhood, gene fusion, cooccurrence, text mining, coexpression, and homology). (B) Upregulated proteins were subjected to enrichment analyses for KEGG and Reactome pathways as well as GO annotation for “Molecular Function” terms using STRING 11.0 tool. Graph indicates the top 29 significantly enriched GO-Molecular Function terms ranked based on -Log10(FDR) ≥3. For all other analysis, FDR ≤0.05 was used as the threshold value, and the number of proteins enriched in each pathway was ≥2. The full list of enriched pathways and terms with associated FDRs is given in supplemental Table 9.

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