Enrichment in LUAD xCell-Derived Clusters (after Adding a Small Margin) by Cell Type, Checkpoint Expression, Methylation, Accessibility, and Survival
(A) Cell type enrichment distributions sorted by significance of two-sided t test for the two clusters (X0, X1), based on xCell lymphoid and myeloid cells, with Benjamini-Hochberg adjusted p value < 1.0 × 10−5 are shown.
(B) Total number of accessible promoter and promoter flank sites in each sample by cluster (two-sided t test p = 1.07 × 10−3) along with total methylation (two-sided t test p = 1.29 × 10−7).
(C) Checkpoint expression distributions, likewise sorted by significance, also point to a general difference in immune landscape between the two groups.
(D and E) (D) All sites with differences in accessibility based on a two-sided t test with Benjamini-Hochberg adjusted p values < 0.01 and (E) < 1.0 × 10−5 are illustrated on the t-SNE plot of promoter and promoter flank facultative sites. Sites with a difference satisfying the thresholds were assigned to the cluster in which they were more accessible.
(F) Accessibility differences are further broken down by how they align with direction of upregulation of corresponding nearby genes (ns gene, no significant difference in matching gene; consistent, direction of significant accessibility and gene expression differences are consistent; inconsistent, direction of significant accessibility and gene expression are inconsistent).
(G) Kaplan-Meier plots demonstrate better survival among X0 (immune hot) patients, shown with log rank test p value and hazard ratio (HR) based on a Cox proportional hazards (CoxPH) model regression using class assignment as the only explanatory variable.
See also Figures S6 and S7, and Tables S4–S7.