Extended Data Fig. 6: Bulk RNA-seq analysis between Brca2^null and Brca1^null tumors after treatment with anti-PD1 yields gene expression programs related to adaptive and innate immune activation enriched in treated Brca2 null tumors.

a, Heatmap displaying all genes significantly differentially expressed (FDR < 0.05) between Brca2^null and Brca1^null murine tumors from the 4T1 model after treatment with anti-PD1. Data show drastic gene expression changes upon Brca2 inactivation with treatment. P-values calculated from two-sided differential expression analysis using DESeq2 (Wald test) and corrected for multiple testing using the Benjamini-Hochberg method. b, Pathway analysis on genes from a using GO pathways. Top enriched pathways in either treated Brca2^null or treated Brca1^null tumors are shown. Color gradient of red to purple indicates decreasing adjusted p-value; circle size indicates number of genes in pathway. GeneRatio on x-axis indicates number of significantly differentially expressed genes from RNA-seq overlapping with genes in each pathway. P-values for overlap between input genes and pathway genesets calculated via hypergeometric test and corrected for multiple comparisons using the Benjamini Hochberg method. c, Heatmap displaying genes significantly differentially expressed in a associated with innate immunity between treated Brca2^null and Brca1^null murine tumors from the 4T1 model. d, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the Bosco interferon antiviral module pathway, evaluated using GSEA (FDR P <= 0.05). e, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the Brown myeloid cell development up pathway, evaluated using GSEA (FDR P <= 0.05). f, Heatmap showing significantly differentially expressed genes (FDR P <= 0.05) between Brca2^null and Brca1^null tumors from the Hecker IFNB1 targets pathway, evaluated using GSEA (FDR P <= 0.05). For c-f, p-values calculated from two-sided differential expression analysis using DESeq2 (Wald test) and correct for multiple testing using the Benjamini-Hochberg method. For all GSEA analyses, p-values calculated using two-sided pre-ranked analysis using log fold changes as input.

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