## ----style, echo = FALSE, results = 'asis'------------------------------------ BiocStyle::markdown() ## ----load_libraries, message=FALSE, warning=FALSE, echo=TRUE------------------ library("dplyr") library("ggplot2") library("viridis") library("tibble") library("gridExtra") library("stringr") library("depmap") library("ExperimentHub") ## ----load_data, message=FALSE, warning=FALSE, echo=TRUE----------------------- ## create ExperimentHub query object eh <- ExperimentHub() query(eh, "depmap") rnai <- eh[["EH3080"]] mutationCalls <- eh[["EH3085"]] metadata <- eh[["EH3086"]] TPM <- eh[["EH3084"]] copyNumber <- eh[["EH3082"]] # crispr <- eh[["EH3081"]] # drug_sensitivity <- eh[["EH3087"]] ## ----soft_tissue_cell_lines, echo=TRUE---------------------------------------- ## list of dependency scores rnai %>% dplyr::select(cell_line, gene_name, dependency) %>% dplyr::filter(stringr::str_detect(cell_line, "SOFT_TISSUE")) %>% dplyr::arrange(dependency) %>% head(10) ## ----message=FALSE, warning=FALSE--------------------------------------------- ## Basic histogram rnai %>% dplyr::select(gene, gene_name, dependency) %>% dplyr::filter(gene_name == "RPL14") %>% ggplot(aes(x = dependency)) + geom_histogram() + geom_vline(xintercept = mean(rnai$dependency, na.rm = TRUE), linetype = "dotted", color = "red") + ggtitle("Histogram of dependency scores for gene RPL14") ## ----message=FALSE, warning=FALSE--------------------------------------------- meta_rnai <- metadata %>% dplyr::select(depmap_id, lineage) %>% dplyr::full_join(rnai, by = "depmap_id") %>% dplyr::filter(gene_name == "RPL14") %>% dplyr::full_join((mutationCalls %>% dplyr::select(depmap_id, entrez_id, is_cosmic_hotspot, var_annotation)), by = c("depmap_id", "entrez_id")) p1 <- meta_rnai %>% ggplot(aes(x = dependency, y = lineage)) + geom_point(alpha = 0.4, size = 0.5) + geom_point(data = subset( meta_rnai, var_annotation == "damaging"), color = "red") + geom_point(data = subset( meta_rnai, var_annotation == "other non-conserving"), color = "blue") + geom_point(data = subset( meta_rnai, var_annotation == "other conserving"), color = "cyan") + geom_point(data = subset( meta_rnai, is_cosmic_hotspot == TRUE), color = "orange") + geom_vline(xintercept=mean(meta_rnai$dependency, na.rm = TRUE), linetype = "dotted", color = "red") + ggtitle("Scatterplot of dependency scores for gene RPL14 by lineage") p1 ## ----message=FALSE, warning=FALSE--------------------------------------------- metadata %>% dplyr::select(depmap_id, lineage) %>% dplyr::full_join(TPM, by = "depmap_id") %>% dplyr::filter(gene_name == "RPL14") %>% ggplot(aes(x = lineage, y = expression, fill = lineage)) + geom_boxplot(outlier.alpha = 0.1) + ggtitle("Boxplot of expression values for gene RPL14 by lineage") + theme(axis.text.x = element_text(angle = 45, hjust=1)) + theme(legend.position = "none") ## ----message=FALSE, warning=FALSE--------------------------------------------- ## expression vs rnai gene dependency for Rhabdomyosarcoma Sarcoma sarcoma <- metadata %>% dplyr::select(depmap_id, cell_line, primary_disease, subtype_disease) %>% dplyr::filter(primary_disease == "Sarcoma", subtype_disease == "Rhabdomyosarcoma") rnai_sub <- rnai %>% dplyr::select(depmap_id, gene, gene_name, dependency) tpm_sub <- TPM %>% dplyr::select(depmap_id, gene, gene_name, expression) sarcoma_dep <- sarcoma %>% dplyr::left_join(rnai_sub, by = "depmap_id") %>% dplyr::select(-cell_line, -primary_disease, -subtype_disease, -gene_name) sarcoma_exp <- sarcoma %>% dplyr::left_join(tpm_sub, by = "depmap_id") sarcoma_dat_exp <- dplyr::full_join(sarcoma_dep, sarcoma_exp, by = c("depmap_id", "gene")) %>% dplyr::filter(!is.na(expression)) p2 <- ggplot(data = sarcoma_dat_exp, aes(x = dependency, y = expression)) + geom_point(alpha = 0.4, size = 0.5) + geom_vline(xintercept=mean(sarcoma_dat_exp$dependency, na.rm = TRUE), linetype = "dotted", color = "red") + geom_hline(yintercept=mean(sarcoma_dat_exp$expression, na.rm = TRUE), linetype = "dotted", color = "red") + ggtitle("Scatterplot of rnai dependency vs expression values for gene") p2 + theme(axis.text.x = element_text(angle = 45)) ## ----------------------------------------------------------------------------- sarcoma_dat_exp %>% dplyr::select(cell_line, gene_name, dependency, expression) %>% dplyr::arrange(dependency) %>% head(10) ## ----message=FALSE, warning=FALSE--------------------------------------------- metadata %>% dplyr::select(depmap_id, lineage) %>% dplyr::full_join(copyNumber, by = "depmap_id") %>% dplyr::filter(gene_name == "RPL14") %>% ggplot(aes(x = lineage, y = log_copy_number, fill = lineage)) + geom_boxplot(outlier.alpha = 0.1) + ggtitle("Boxplot of log copy number for gene RPL14 by lineage") + theme(axis.text.x = element_text(angle = 45, hjust = 1)) + theme(legend.position = "none") ## ----echo = FALSE------------------------------------------------------------- sessionInfo()