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. Author manuscript; available in PMC: 2021 Nov 24.
Published in final edited form as: Circulation. 2020 Oct 9;142(21):2029–2044. doi: 10.1161/CIRCULATIONAHA.120.045810

Figure 2. Protein Clusters Identified by Weighted Co-expression Network Analyses in PROMIS-HFpEF Derivation Cohort and the Northwestern Validation Cohort.

Figure 2.

(A) Adjacency network-map of circulating proteins color-coded by cluster assignment by hierarchical clustering-based nearness or co-expression of proteins. For clarity of presentation only nodes (proteins) that were assigned to a cluster are shown (N=159/248); the remaining proteins lie on the outer edges of the network-map. (B) Overrepresented, non-redundant pathways in each cluster with false discovery rate corrected P-values. (C) Detailed network-maps of proteins in the 3 clusters that were representative of inflammation (i.e., overrepresentation of ≥2 inflammatory pathways). Node size reflects intra-cluster connectivity (i.e., the sum of weighted edges [correlations] with all other proteins in the cluster). Node color density reflects the strength of cluster membership. Edge thickness and transparency reflect the adjacency of proteins according to weighted co-expressions. (D) Summary of extracted clusters including (1) the number of assigned proteins per cluster, (2) the main hub (based on intra-cluster connectivity), (3) other exemplar proteins, the primary (most significant) overrepresented pathway; (4) the number of significantly upregulated inflammatory pathway; and (5) the cross-cohort conservation in the HFpEF patients in the Northwestern validation cohort, reflected by the number of overlapping proteins and corresponding P-value (tested under a hypergeometric distribution). (E) Adjacency network-map of circulating proteins in the Northwestern HFpEF patients in the validation cohort. Clusters with most significant overlap were assigned the same color as the corresponding cluster in PROMIS-HFpEF cohort. (F) Adjacency network-map of circulating proteins in the Northwestern control patients in the validation cohort. Cluster preservation was tested against the Northwestern HFpEF patients; clusters with significant overlap were assigned the same color as the corresponding cluster in the Northwestern HFpEF patients.