## ---- message=FALSE, warning=FALSE--------------------------------------- library(crossmeta) library(ccmap) # microarray data from studies using drug LY-294002 library(lydata) data_dir <- system.file("extdata", package = "lydata") # gather all GSEs gse_names <- c("GSE9601", "GSE15069", "GSE50841", "GSE34817", "GSE29689") # load previous crossmeta differential expression analysis anals <- load_diff(gse_names, data_dir) # run meta-analysis es <- es_meta(anals) # contribute your signature to our public meta-analysis database # contribute(anals, subject = "LY-294002") # extract moderated adjusted standardized effect sizes dprimes <- get_dprimes(es) # query signature query_sig <- dprimes$all$meta ## ---- message=FALSE, warning=FALSE--------------------------------------- library(ccdata) # load drug signatures data(cmap_es) ## ---- message=FALSE, warning=FALSE--------------------------------------- # load drug signatures data(l1000_es) ## ---- message=FALSE, warning=FALSE--------------------------------------- top_cmap <- query_drugs(query_sig, cmap_es) top_l1000 <- query_drugs(query_sig, l1000_es) # LY-294002 best match among 1309 cmap signatures # other PI3K inhibitors are also identified among top matching drugs head(top_cmap, 4) # LY-294002 matches 4 of top 10 l1000 signatures (230,829 total) # other PI3K inhibitors are also identified among top matching drugs head(top_l1000, 4) ## ---- message=FALSE, warning=FALSE--------------------------------------- # remove genes in cmap_es that are not measured in l1000_es cmap_lm <- cmap_es[row.names(l1000_es), ] # query using genes common to cmap_es and l1000_es top_cmap_lm <- query_drugs(query_sig, cmap_lm) ## ---- message=FALSE, warning=FALSE--------------------------------------- # query all 856086 combinations (takes ~2 minutes on Intel Core i7-6700) # top_combos <- query_combos(query_sig, cmap_es) # query only combinations with LY-294002 top_combos <- query_combos(query_sig, cmap_es, include='LY-294002', ncores=1) ## ---- message=FALSE, warning=FALSE--------------------------------------- # query only combinations with LY-294002_NKDBA_10um_24h top_combos <- query_combos(query_sig, l1000_es, include='LY-294002_NKDBA_10um_24h', ncores=1) # query combinations with all LY-294002 signatures # top_combos <- query_combos(query_sig, l1000_es, include='LY-294002') ## ---- message=FALSE, warning=FALSE--------------------------------------- # Times on Intel Core i7-6700 with MRO+MKL # requires ~8-10GB of RAM method <- 'ml' include <- names(head(top_cmap)) # query all 856086 combinations (~2 hours) # top_combos <- query_combos(query_sig, 'cmap', method) # query combinations with top single drugs (~1 minute) # top_combos <- query_combos(query_sig, 'cmap', method, include) sessionInfo()