Modulation of the Host Cell Transcriptome and Epigenome by Fusobacterium nucleatum

Figures

• 

  FIG 1. Comparison of HCE and HCAE cell protein-coding genes differentially expressed in response to various F. nucleatum (Fn) strains. Upset plots highlight the number of shared and unique significantly differentially expressed upregulated (A) and downregulated (B) genes. Horizontal bars at the bottom left of each plot show the total number of significantly differentially expressed genes under each condition. Vertical bars show the number of unique or shared genes between each comparison, with conditions included in each comparison shown by the respective filled points below.

• 

  FIG 2. Differential expression gene sets of interest and related pathways. (A) Scatterplot and gene set assignments of DE genes for HCE and HCAE cells. For all genes that were significantly DE (adjusted P ≤ 0.05) under at least 1 condition, the mean and standard deviation of DE genes for each IP cell exposed to three different F. nucleatum strains were calculated (nonsignificant DE gene log2FC = 0) (crossbars denote standard deviations). Genes with an average log2FC of greater than 3 (upregulated) or less than −0.75 (downregulated) were considered genes of interest (colored points) (the top 5 genes of each group are labeled). Genes meeting these criteria in both cell lines were considered to be conserved upregulated or downregulated genes of interest. Genes meeting these criteria in one cell line and not significantly DE in the other cell line were considered cell line-specific genes of interest. (B) Gene set enrichment analysis (GSEA) of gene sets of interest. Ensembl gene names of each gene set were used separately as inputs for EnrichR GSEA, querying the GO biological process library. Significant resulting GO terms (adjusted P ≤ 0.05) were ranked by combined score (up to 10 terms…

• 

  FIG 3. Gene set enrichment analysis (GSEA) of all significantly differentially expressed human protein-coding genes in response to various F. nucleatum (Fn) strains. The y axis shows the top 25 GO terms for upregulated (A) and downregulated (B) gene sets for all conditions (ranked by the sum of the “total score” of significant GO terms from all conditions from top [highest] to bottom [lowest]). Significant GO term total scores (adjusted P value of ≤0.05) are colored (orange, upregulated; blue, downregulated), and nonsignificant GO term total scores are shown in gray. The size of the dot reflects the score of the GO term for each condition.

• 

  FIG 4. Epigenetic profiling of HCE and HCAE cells exposed to F. nucleatum (Fn) 7/1. (A) Bar plots showing the fraction of the genome that contains each histone mark (x axis) in control (light gray) and F. nucleatum 7/1-exposed (dark gray) HCE (top) and HCAE (bottom) cells. The bar height is the mean from three replicates, with the error bar extending to the mean and the standard deviation. (B) Summary of the 10-state ChromHMM model emission parameters (left) and genomic annotation enrichments (right). The intensity of blue correlates with increasing values of the emission parameter or fold enrichment. (C) Bar plots showing the fraction of the entire genome that is classified as each state (x axis) in control (light gray) and F. nucleatum 7/1-exposed (dark gray) HCE (top) and HCAE (bottom) cells. The bar height is the mean from the three replicates, with the error bar extending to the mean and the standard deviation. The Quies/NS state is shown in its own panel with a different y axis scale. (D and E) Sankey diagrams showing the changes in states for every window in the unexposed (top) and F. nucleatum 7/1-exposed (bottom) HCE (D) and HCAE (E) cells. Bar sizes for each state are…