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. 2021 Jun 16;12:3669. doi: 10.1038/s41467-021-23925-z

Fig. 3. HRV-C15 shifts host cell metabolism towards fatty acid biosynthesis.

Fig. 3

a Hierarchical clustering heatmap depicting metabolite concentration (Top 25) of HRV-C15 (HRV+) and noninfected (HRV−) ALI cultures at 4, 12, and 24 h post infection normalized to noninfected control group at 4 h. Distance measure: Euclidean. Clustering algorithm: ward, n = 6 donors. b Heatmap depicting group averages of metabolite concentration (Top 25) of HRV-C15 (HRV+) and noninfected (HRV−) ALI cultures at 24 h post infection normalized to noninfected control group at 24 h. Distance measure: Euclidean. Clustering algorithm: ward, n = 6 donors. c Enrichment analysis of upregulated metabolites computed by Hits/Expected (hits = observed hits; expected = expected hits) of HRV-C15 (HRV+) and noninfected (HRV−) ALI cultures at 24 h post infection normalized to the HRV− group. Data were analyzed using MetaboAnalyst 4.0, Small Molecule Pathway Database (SMPDB) metabolite set library: phosphatidylcholine biosynthesis ***p = 2.54e − 5, sphingolipid metabolism ***p = 3.02e − 4, phosphatidylethanolamine biosynthesis ***p = 3.02e − 4, fatty acid biosynthesis *p = 0.004, n = 6 donors. d 3-Hydroxybutanoic acid, ethanolamine phosphate, l-serine, and alpha-d-glucose relative abundance during HRV-C15 infection in ALI cultures over 24 h determined by LC-MS. Data are represented as boxplots and analyzed by two-tailed paired t test: 3-hydroxybutanoic acid **p = 0.006, ethanolamine phosphate ***p = 0.0005, l-serine *p = 0.015, alpha-d-glucose *p = 0.023, n = 6 donors. e Integrated metabolic pathway analysis on the data obtained from combined metabolomics and proteomics. Enrichment analysis by hypergeometric test and topology measured degree centrality. Combine queries integration method. The overviews show all matched pathways according to the p values from the pathway enrichment analysis and pathway impact values from the pathway topology analysis. Data represented as boxplots indicate the median (center line), upper and lower box bounds (IQR = first and third quartiles), and whiskers (min and max values), with individual donor data points superimposed onto the boxplot.