From b1c2ec26fea0a2fedc549b6c6386a38714f56183 Mon Sep 17 00:00:00 2001 From: leaffur Date: Mon, 29 Sep 2025 02:31:56 -0400 Subject: [PATCH 1/2] pre-filtering improvement --- CASE_R_package.Rproj | 1 + R/CASE.R | 22 +++++++++++++++++++--- R/CASE_models.R | 27 +++++++++++++++++---------- data/example_data.rda | Bin 58896 -> 58903 bytes 4 files changed, 37 insertions(+), 13 deletions(-) diff --git a/CASE_R_package.Rproj b/CASE_R_package.Rproj index 21a4da0..1bb667d 100644 --- a/CASE_R_package.Rproj +++ b/CASE_R_package.Rproj @@ -1,4 +1,5 @@ Version: 1.0 +ProjectId: 2241ace3-378b-4e48-bb0a-ef8f1b97ac60 RestoreWorkspace: Default SaveWorkspace: Default diff --git a/R/CASE.R b/R/CASE.R index 6cb96e2..7b9e197 100644 --- a/R/CASE.R +++ b/R/CASE.R @@ -81,14 +81,30 @@ CASE <- function(Z = NULL, R, hatB = NULL, hatS = NULL, N, V = NULL, cs = TRUE, hatS = hatBS$hatS # V = estimate_null_correlation_simple(mash_set_data(do.call(rbind, raw.data$hatB), do.call(rbind, raw.data$hatS))) - - m1 <- CASE_train(hatB = hatB, hatS = hatS, V = V, R = R, N = N, Z = NULL, verbose = verbose, ...) + sump = 2 - 2 * pnorm(abs(hatB / hatS)) + sumfdr = apply(sump, 2, function(x) p.adjust(x, method = "fdr")) + C = ncol(sumfdr) + + # no strong signals in all cell types, or low SNP numbers + if (sum(sumfdr <= 0.2) == 0){ + if (verbose){ + cat("No FDR-significant variants in the inputs.", "\n") + } + m1 = list(pi = 1, n.iter = 0) + } else if (nrow(sump) <= 20){ + if (verbose){ + cat("Too few SNPs in the data (<=20).", "\n") + } + m1 = list(pi = 1, n.iter = 0) + } else{ + m1 <- CASE_train(hatB = hatB, hatS = hatS, V = V, R = R, N = N, Z = NULL, verbose = verbose, ...) + } res <- CASE_test(hatB = hatB, hatS = hatS, R = R, N = N, CASE_training = m1, Z = NULL, verbose = verbose, ...) t2 = Sys.time() res$time = difftime(t2, t1, units = "secs") if (cs){ - res$sets <- get_credible_sets(res$pip, R = R, verbose = verbose) + res$sets <- get_credible_sets(pips = res$pip, R = R, verbose = verbose) } return(res) diff --git a/R/CASE_models.R b/R/CASE_models.R index 1cdb8be..fb22f16 100644 --- a/R/CASE_models.R +++ b/R/CASE_models.R @@ -80,10 +80,17 @@ CASE_train <- function(Z = NULL, R, hatB = NULL, hatS = NULL, N, V = NULL, verbo ## Train with only marginally significant SNPs M0 = nrow(R) ME_p <- 2 - 2 * pnorm(abs(hatB / hatS), 0, 1) - significant_thres = ifelse("significant_thres" %in% names(args), args$significant_thres, 1e-1) - idx <- which(ME_p <= significant_thres, arr.ind = TRUE)[, 1] %>% unique + significant_thres = ifelse("significant_thres" %in% names(args), + args$significant_thres, + ifelse(sqrt(6) / sqrt(diag(N)) >= 0.05, sqrt(6) / sqrt(diag(N)), 0.05)) + if (C == 1){ + idx <- which(ME_p <= significant_thres) + } else{ + idx <- which(t(apply(ME_p, 1, function(x) x <= significant_thres)), arr.ind = TRUE)[, 1] %>% unique + } + if (length(idx) == 1){ - idx = c(idx - 1, idx, idx + 1) + idx = idx + (-2):2 idx = idx[idx >= 1 & idx <= nrow(hatB)] } hatB = hatB[idx, ] @@ -96,7 +103,7 @@ CASE_train <- function(Z = NULL, R, hatB = NULL, hatS = NULL, N, V = NULL, verbo if (verbose){ cat("No marginally significant variants in the inputs.", "\n") } - return(list(pi = 1, U = list(matrix(0, C, C)), V = V, n.iter = 0)) + return(list(pi = 1, n.iter = 0)) } J <- 0 @@ -310,10 +317,6 @@ CASE_test <- function(Z = NULL, R, hatB = NULL, hatS = NULL, N, CASE_training, v cat("Start Posterior Analysis.", "\n") } - U = CASE_training$U - V = CASE_training$V - pi = CASE_training$pi - if (is.null(Z)){ Z = hatB / hatS } @@ -322,15 +325,19 @@ CASE_test <- function(Z = NULL, R, hatB = NULL, hatS = NULL, N, CASE_training, v hatBS = transform_Z(Z, N) hatB = hatBS$hatB hatS = hatBS$hatS - + C <- ncol(hatB) M <- nrow(R) + pi = CASE_training$pi if (length(pi) <= 1){ post_mean = pip = matrix(0, M, C) - return(list(pi = pi, U = U, V = V, pip = pip, post_mean = post_mean)) + return(list(pip = pip, post_mean = post_mean)) } + U = CASE_training$U + V = CASE_training$V + L = length(U) ## MC 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zIk3g(2++lCTV-5JkK2{y;O`i#l|MtVwSRK$ds-LR=9?I-wrFn0metE8`At*PwHQ37 zj>jE3t`1+Un`w`O46e`58pd?>m|DhiEfa|0`j-=l_Qit$QU?_6Fdok0ic(hDMj>c} zEUXBD40cJO;7brxj2$7~BcbOWY?#?8It;=gCBQb|>~<$q$)%VV`9FCDK>2+>-9jJ$ zY=IQ};Z^@XzZC=hzcwG9Ko7t0{W?&6umAxTqC)(B^ttlbMJT`#M3MjmfC^Ydm`NmF PAI02}P81{>5PJ~7WRV-D From 702bdf35df6d92c0d68ec7e69ebe501165051fe7 Mon Sep 17 00:00:00 2001 From: leaffur Date: Mon, 29 Sep 2025 02:46:54 -0400 Subject: [PATCH 2/2] pre-filtering improvement --- DESCRIPTION | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/DESCRIPTION b/DESCRIPTION index a479035..3405390 100644 --- a/DESCRIPTION +++ b/DESCRIPTION @@ -1,7 +1,7 @@ Type: Package Package: CASE Title: Cell-type-specific And Shared EQTL fine-mapping -Version: 0.3.0 +Version: 0.3.1 Authors@R: c( person("Chen", "Lin", , "c.lin@yale.edu", role = c("aut", "cre"), comment = c(ORCID = "0000-0001-9821-2578")), @@ -18,7 +18,7 @@ Imports: mvtnorm, stats Encoding: UTF-8 -RoxygenNote: 7.3.1 +RoxygenNote: 7.3.2 Suggests: knitr, rmarkdown,