diff --git a/dap_src/CMakeLists.txt b/dap_src/CMakeLists.txt new file mode 100644 index 0000000..df27914 --- /dev/null +++ b/dap_src/CMakeLists.txt @@ -0,0 +1,27 @@ +cmake_minimum_required(VERSION 3.2) +project (dap-g VERSION 0.0.1) + +set(CMAKE_CXX_STANDARD 11) +execute_process(COMMAND date OUTPUT_VARIABLE DATE OUTPUT_STRIP_TRAILING_WHITESPACE) +execute_process(COMMAND whoami OUTPUT_VARIABLE USER OUTPUT_STRIP_TRAILING_WHITESPACE) + +add_definitions(-DVERSION="${PROJECT_VERSION}" -DUSER="${USER}" -DDATE="${DATE}") + +find_package(OpenMP) +if (OPENMP_FOUND) + set(CMAKE_C_FLAGS "${CMAKE_C_FLAGS} ${OpenMP_C_FLAGS}") + set(CMAKE_CXX_FLAGS "${CMAKE_CXX_FLAGS} ${OpenMP_CXX_FLAGS}") +endif() + +find_package(GSL REQUIRED) + +add_executable(dap-g + src/main.cc + src/MLR.h src/MLR.cc + src/parser.h src/parser.cc + src/controller.h src/controller.cc +) + +target_link_libraries(dap-g PUBLIC GSL::gsl GSL::gslcblas) + +install(TARGETS dap-g RUNTIME DESTINATION bin) \ No newline at end of file diff --git a/dap_src/Makefile b/dap_src/Makefile deleted file mode 100644 index 3ecf35d..0000000 --- a/dap_src/Makefile +++ /dev/null @@ -1,14 +0,0 @@ -main: main.o controller.o parser.o MLR.o - g++ -fopenmp -O3 main.o parser.o controller.o MLR.o -lm -L/usr/local/lib -lgsl -lgslcblas -o dap-g -static: main.o controller.o parser.o MLR.o - g++ -fopenmp -O3 main.o parser.o controller.o MLR.o -lm -L/usr/local/lib -lgsl -lgslcblas -static -o dap-g.static -main.o: main.cc - g++ -c -O3 main.cc -parser.o: parser.cc parser.h - g++ -c -O3 parser.cc -controller.o: controller.cc controller.h - g++ -c -O3 -fopenmp controller.cc -MLR.o: MLR.cc MLR.h - g++ -c -O3 MLR.cc -clean: - rm *.o dap-g diff --git a/dap_src/R-package/DESCRIPTION b/dap_src/R-package/DESCRIPTION new file mode 100644 index 0000000..f7804d7 --- /dev/null +++ b/dap_src/R-package/DESCRIPTION @@ -0,0 +1,17 @@ +Package: dap +Type: Package +Title: Structured Bayesian Model Selection via Adaptive DAP Algorithm +Version: 0.1.0 +Author: William Wen, Ketian Yu +Maintainer: Ketian Yu +Description: An implementations of structured Bayesian model selection via adaptive deterministic approximation of posteriors (DAP) algorithm. + Applications include genetic association analysis integrating genomic annotations. + These methods are designed to perform rigorous enrichment analysis, QTL discovery and multi-SNP fine-mapping analysis in a highly efficient way. +License: GPL-3 +Encoding: UTF-8 +LazyData: true +LinkingTo: + Rcpp +Imports: + Rcpp +RoxygenNote: 6.1.1 diff --git a/dap_src/R-package/LICENSE.md b/dap_src/R-package/LICENSE.md new file mode 100644 index 0000000..280ea5b --- /dev/null +++ b/dap_src/R-package/LICENSE.md @@ -0,0 +1,595 @@ +GNU General Public License +========================== + +_Version 3, 29 June 2007_ +_Copyright © 2007 Free Software Foundation, Inc. <>_ + +Everyone is permitted to copy and distribute verbatim copies of this license +document, but changing it is not allowed. + +## Preamble + +The GNU General Public License is a free, copyleft license for software and other +kinds of works. + +The licenses for most software and other practical works are designed to take away +your freedom to share and change the works. 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No Surrender of Others' Freedom + +If conditions are imposed on you (whether by court order, agreement or otherwise) +that contradict the conditions of this License, they do not excuse you from the +conditions of this License. If you cannot convey a covered work so as to satisfy +simultaneously your obligations under this License and any other pertinent +obligations, then as a consequence you may not convey it at all. For example, if you +agree to terms that obligate you to collect a royalty for further conveying from +those to whom you convey the Program, the only way you could satisfy both those terms +and this License would be to refrain entirely from conveying the Program. + +### 13. Use with the GNU Affero General Public License + +Notwithstanding any other provision of this License, you have permission to link or +combine any covered work with a work licensed under version 3 of the GNU Affero +General Public License into a single combined work, and to convey the resulting work. +The terms of this License will continue to apply to the part which is the covered +work, but the special requirements of the GNU Affero General Public License, section +13, concerning interaction through a network will apply to the combination as such. + +### 14. Revised Versions of this License + +The Free Software Foundation may publish revised and/or new versions of the GNU +General Public License from time to time. Such new versions will be similar in spirit +to the present version, but may differ in detail to address new problems or concerns. + +Each version is given a distinguishing version number. If the Program specifies that +a certain numbered version of the GNU General Public License “or any later +version” applies to it, you have the option of following the terms and +conditions either of that numbered version or of any later version published by the +Free Software Foundation. If the Program does not specify a version number of the GNU +General Public License, you may choose any version ever published by the Free +Software Foundation. + +If the Program specifies that a proxy can decide which future versions of the GNU +General Public License can be used, that proxy's public statement of acceptance of a +version permanently authorizes you to choose that version for the Program. + +Later license versions may give you additional or different permissions. However, no +additional obligations are imposed on any author or copyright holder as a result of +your choosing to follow a later version. + +### 15. Disclaimer of Warranty + +THERE IS NO WARRANTY FOR THE PROGRAM, TO THE EXTENT PERMITTED BY APPLICABLE LAW. +EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT HOLDERS AND/OR OTHER PARTIES +PROVIDE THE PROGRAM “AS IS” WITHOUT WARRANTY OF ANY KIND, EITHER +EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF +MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. THE ENTIRE RISK AS TO THE +QUALITY AND PERFORMANCE OF THE PROGRAM IS WITH YOU. SHOULD THE PROGRAM PROVE +DEFECTIVE, YOU ASSUME THE COST OF ALL NECESSARY SERVICING, REPAIR OR CORRECTION. + +### 16. Limitation of Liability + +IN NO EVENT UNLESS REQUIRED BY APPLICABLE LAW OR AGREED TO IN WRITING WILL ANY +COPYRIGHT HOLDER, OR ANY OTHER PARTY WHO MODIFIES AND/OR CONVEYS THE PROGRAM AS +PERMITTED ABOVE, BE LIABLE TO YOU FOR DAMAGES, INCLUDING ANY GENERAL, SPECIAL, +INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING OUT OF THE USE OR INABILITY TO USE THE +PROGRAM (INCLUDING BUT NOT LIMITED TO LOSS OF DATA OR DATA BEING RENDERED INACCURATE +OR LOSSES SUSTAINED BY YOU OR THIRD PARTIES OR A FAILURE OF THE PROGRAM TO OPERATE +WITH ANY OTHER PROGRAMS), EVEN IF SUCH HOLDER OR OTHER PARTY HAS BEEN ADVISED OF THE +POSSIBILITY OF SUCH DAMAGES. + +### 17. Interpretation of Sections 15 and 16 + +If the disclaimer of warranty and limitation of liability provided above cannot be +given local legal effect according to their terms, reviewing courts shall apply local +law that most closely approximates an absolute waiver of all civil liability in +connection with the Program, unless a warranty or assumption of liability accompanies +a copy of the Program in return for a fee. + +_END OF TERMS AND CONDITIONS_ + +## How to Apply These Terms to Your New Programs + +If you develop a new program, and you want it to be of the greatest possible use to +the public, the best way to achieve this is to make it free software which everyone +can redistribute and change under these terms. + +To do so, attach the following notices to the program. It is safest to attach them +to the start of each source file to most effectively state the exclusion of warranty; +and each file should have at least the “copyright” line and a pointer to +where the full notice is found. + + + Copyright (C) 2019 Ketian Yu + + This program is free software: you can redistribute it and/or modify + it under the terms of the GNU General Public License as published by + the Free Software Foundation, either version 3 of the License, or + (at your option) any later version. + + This program is distributed in the hope that it will be useful, + but WITHOUT ANY WARRANTY; without even the implied warranty of + MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the + GNU General Public License for more details. + + You should have received a copy of the GNU General Public License + along with this program. If not, see . + +Also add information on how to contact you by electronic and paper mail. + +If the program does terminal interaction, make it output a short notice like this +when it starts in an interactive mode: + + dap Copyright (C) 2019 Ketian Yu + This program comes with ABSOLUTELY NO WARRANTY; for details type 'show w'. + This is free software, and you are welcome to redistribute it + under certain conditions; type 'show c' for details. + +The hypothetical commands `show w` and `show c` should show the appropriate parts of +the General Public License. Of course, your program's commands might be different; +for a GUI interface, you would use an “about box”. + +You should also get your employer (if you work as a programmer) or school, if any, to +sign a “copyright disclaimer” for the program, if necessary. For more +information on this, and how to apply and follow the GNU GPL, see +<>. + +The GNU General Public License does not permit incorporating your program into +proprietary programs. If your program is a subroutine library, you may consider it +more useful to permit linking proprietary applications with the library. If this is +what you want to do, use the GNU Lesser General Public License instead of this +License. But first, please read +<>. diff --git a/dap_src/R-package/NAMESPACE b/dap_src/R-package/NAMESPACE new file mode 100644 index 0000000..58a4502 --- /dev/null +++ b/dap_src/R-package/NAMESPACE @@ -0,0 +1,17 @@ +# Generated by roxygen2: do not edit by hand + +S3method(print,dap) +S3method(print,summary.dap) +S3method(summary,dap) +export(dap) +export(dap.sbams) +export(dap.ss) +export(dap.z) +export(extract.sbams) +export(model.dap) +export(read.sbams) +export(scan) +export(scan.sbams) +export(twas) +importFrom(Rcpp,sourceCpp) +useDynLib(dap, .registration = TRUE) diff --git a/dap_src/R-package/R/RcppExports.R b/dap_src/R-package/R/RcppExports.R new file mode 100644 index 0000000..f1b9e2c --- /dev/null +++ b/dap_src/R-package/R/RcppExports.R @@ -0,0 +1,15 @@ +# Generated by using Rcpp::compileAttributes() -> do not edit by hand +# Generator token: 10BE3573-1514-4C36-9D1C-5A225CD40393 + +dap_main <- function(input_format, arg, quiet) { + .Call(`_dap_dap_main`, input_format, arg, quiet) +} + +read_sbams <- function(data_file) { + .Call(`_dap_read_sbams`, data_file) +} + +extract_sbams <- function(arg) { + .Call(`_dap_extract_sbams`, arg) +} + diff --git a/dap_src/R-package/R/main.R b/dap_src/R-package/R/main.R new file mode 100644 index 0000000..bbda258 --- /dev/null +++ b/dap_src/R-package/R/main.R @@ -0,0 +1,456 @@ +#' Structured Bayesian Model Selection via Deterministic Approximation of Posteriors +#' +#' \code{dap} is used perform Bayesian variable selection among a large scale of predictors, multicolinearty and missingness are allowed. It will automatically impute missingness in the input data with mean values, normalize the response and predictors, and propose top predictive signals and signal clusters according to posterior probability. +#' +#' @aliases dap +#' @param formula an object of class \code{formula} (or one that can be coerced to that class): a symbolic description of the model to be fitted. +#' @param data a \code{data.frame} containing the variables in the model. +#' @param prior (optional) a \code{data.frame} with 1st column as snp names, and 2nd column as prior probabilities. If any snp in \code{data} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{data}. +#' @param ens (optional) prior expected number of signals, \code{ens=1} by default. +#' @param pi1 (optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output. +#' @param size_limit (optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation. +#' @param thread (optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option. +#' @param quiet (optional) If TRUE, dap will mute running logs. +#' @return \code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +#' \item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +#' \item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +#' \item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +#' \item{model.summary}{a list of information on candidate models:\describe{ +#' \item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +#' \item{model.size}{information on expected model size and corresponding standard deviation.} +#' \item{log10NC}{log10 normalizing constant.} +#' \item{PIP.min}{the minimum posterior inclusion probability.} +#' \item{N}{the sample size.} +#' \item{response}{the name of the phenotype/response variable.}}} +#' \item{call}{the matched call.} +#' @examples +#' set.seed(0) +#' n = 100 +#' p = 1000 +#' +#' a1 = rnorm(n) +#' a2 = 10*a1+rnorm(n) +#' a3 = 2*a1+9*a2+rnorm(n) +#' +#' b1 = rnorm(n) +#' b2 = 8*b1+rnorm(n) +#' +#' x = matrix(rnorm(n*(p-5)), nrow=n) +#' +#' df = data.frame(a1,a2,a3,b1,b2,x) +#' df$y = 2*a1+b1+rnorm(n) +#' +#' test.dap = dap(y~., df) +#' test.dap +#' +#' summary(test.dap) +#' +#' +#' ### example with prior #### +#' prior = data.frame(snp=c("a1","b1"), prior=c(0.5,0.5)) +#' dap(y~., df, prior=prior) +#' +#' @details Please refer to \url{https://github.com/xqwen/dap/tree/master/dap_src} for more details. +#' @seealso Please see \code{\link{summary.dap}} for summaries; and \code{\link{dap.sbams}} for a different interface directly analyzing a sbams-format file. +#' @references Wen, X., Lee, Y., Luca, F., Pique-Regi, R. Efficient Integrative Multi-SNP Association Analysis using Deterministic Approximation of Posteriors. \emph{The American Journal of Human Genetics}, 98(6), 1114--1129 +#' @references Lee, Y, Luca, F, Pique-Regi, R,Wen, X. Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics bioRxiv:316471 +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +dap = function(formula, data, prior=NULL, ens=1, pi1=-1, ld_control=0.25, msize=-1, converg_thresh=0.01, all=FALSE, size_limit=-1, thread=1, quiet=FALSE){ + cl = match.call() + mf = match.call(expand.dots = FALSE) + m <- match(c("formula", "data"), names(mf), 0L) + mf <- mf[c(1L, m)] + mf$drop.unused.levels <- TRUE + mf[[1L]] <- quote(stats::model.frame) + mf <- eval(mf, parent.frame()) + mt <- attr(mf, "terms") + + y = model.response(mf, "numeric") + attr(mt, "intercept") = 0 + x <- model.matrix(mt, mf) + + # impute with mean + y[is.na(y)] = mean(y, na.rm = TRUE) + x = apply(x, 2, function(t) replace(t, is.na(t), mean(t, na.rm=TRUE))) + + params = list(x=x, y=y, pheno_name=all.vars(cl)[1]) + + if(!is.null(prior)){ + if(class(prior)=="data.frame"){ + if(nrow(prior)>0 & ncol(prior)>1){ + params$has_prior = TRUE + params$prior_snp_names = prior[,1] + params$prior_values = prior[,2] + } + } + } + + if(class(ens)=="numeric" & ens > 0) params$ens=ens + if(class(pi1)=="numeric" & pi1>0 & pi1<1) params$pi1=pi1 + if(class(ld_control)=="numeric" & ld_control>=0 & ld_control<1) params$ld_control=ld_control + if(class(msize)=="numeric" & as.integer(msize) >= 1) params$msize=as.integer(msize) + if(class(converg_thresh)=="numeric" & converg_thresh>=0) params$converg_thresh=converg_thresh + if(class(all)=="logical" & all) params$all=1 + if(class(size_limit)=="numeric" & size_limit>=1) params$size_limit=size_limit + if(class(thread)=="numeric" & as.integer(thread)>1) params$t=as.integer(thread) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap',2, params, as.numeric(quiet)) + + result$call = cl + result$model.summary$model$configuration = gsub("&", "+", result$model.summary$model$configuration) + + class(result) = "dap" + return(result) +} + +#' @export +print.dap = function(object, digits = max(3L, getOption("digits") - 3L)){ + cat("\nCall:\n", + paste(deparse(object$call), sep = "\n", collapse = "\n"), "\n\n", sep = "") + + cat("Posterior expected model size:", format(object$model.summary$model.size[1], digits=digits), "( sd =", format(object$model.summary$model.size[2], digits=digits), ")\n") + cat("LogNC =", format(object$model.summary$log10NC/log10(exp(1)), digits=digits), "( Log10NC =", format(object$model.summary$log10NC, digits=digits), ")\n") + cat("Minimum PIP is estimated at", format(object$model.summary$PIP.min, digits=digits), "( N =", format(object$model.summary$N, digits=digits), ")\n") + + if(length(object$signal.cluster)){ + cat("\nIndependent Association Signal Clusters:\n") + signals = sapply(1:nrow(object$signal.cluster$cluster.summary), function(t) paste(sort(object$variant[object$variant$cluster==t,"predictor"]), collapse =" ")) + print(format(data.frame(object$signal.cluster$cluster.summary, member.predictors=signals), digits=digits), print.gap=2L, quote=FALSE) + }else{ + cat("\nNo Independent Association Signal Clusters.\n") + } + + cat("\nOne of the best models is:\n") + cat("\t", object$model.summary$response,"~", gsub("&", " + ", object$model.summary$model$configuration[1]), "\n\n") + + cat("Please refer to $variant for PIP of top predictors,\n") + cat(" and model.dap() for configuration of top models.\n") + + cat("\n") + invisible(object) +} + +#' Summarizing DAP results +#' +#' \code{summary} method for class \code{"dap"}. +#' @aliases summary.dap +#' @aliases print.summary.dap +#' @usage +#' \method{summary}{dap}(object) +#' +#' \method{print}{summary.dap}(object, digits = max(5L, getOption("digits") - 3L)) +#' @param object an object of class \code{"dap"}, usually, a result of a call to \code{\link{dap}}. +#' @param digits the number of significant digits to use when printing. +#' @return The function \code{summary.dap} returns a summary of dap results given in \code{object}, using its components \code{"call"} and \code{"info"}, plus \item{top.models}{a data frame for the top 5 (or less if not available) models with highest posterior probabilities, including model configuration, number of predictors involved, the posterior probability of the corresponding model, and the unnormalized posterior score of the model, defined as \eqn{log10(model prior)+log10(BF)}.} +#' \item{clusters}{a data frame for the signal cluster summary, including the size of the cluster (i.e. the number of member predictors), the corresponding posterior inclusion probability, and the remaining columns represent the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.} +#' \item{signals}{a list of data frames for predictors in each cluster, including the predictor name, and corresponding posterior inclusion probability.} +#' @export +summary.dap = function(object){ + if(!inherits(object, "dap")) + warning("calling summary.dap() ...") + + ans = list() + ans$call = object$call + ans$info = object$model.summary[-1] + + n_top_model = min(5, nrow(object$model.summary$model)) + model = sapply(1:n_top_model, function(i) gsub("&", " + ", object$model.summary$model$configuration[i])) + ans$top.models = data.frame(model, object$model.summary$model[1:n_top_model,c(2,1,3)]) + + if(length(object$signal.cluster)){ + ncluster = nrow(object$signal.cluster$cluster.summary) + ans$clusters = data.frame(object$signal.cluster$cluster.summary[,-3], object$signal.cluster$cluster.r2) + names(ans$clusters) = c(names(ans$clusters)[1:2], "r2 matrix", rep("", ncluster-1)) + + for(i in 1:ncluster){ + ans$signals[[i]] = object$variant[object$variant$cluster==i,-4] + row.names(ans$signals[[i]]) = 1:nrow(ans$signals[[i]]) + } + } + + class(ans) = "summary.dap" + return(ans) +} + +#' @export +print.summary.dap = function(object, digits = max(5L, getOption("digits") - 3L)){ + cat("\nCall:\n", + paste(deparse(object$call), sep = "\n", collapse = "\n"), "\n\n", sep = "") + + cat("Posterior expected model size:", format(object$info$model.size[1], digits=digits), "( sd =", format(object$info$model.size[2], digits=digits), ")\n") + cat("LogNC =", format(object$info$log10NC/log10(exp(1)), digits=digits), "( Log10NC =", format(object$info$log10NC, digits=digits), ")\n") + cat("Minimum PIP is estimated at", format(object$info$PIP.min, digits=digits), "( N =", format(object$info$N, digits=digits), ")\n") + + cat("\nTop Models:\n") + print(format(object$top.models, digits=digits), print.gap=2L, quote=FALSE) + cat("\n") + + + if(length(object$clusters)){ + cat("\nIndependent Association Signal Clusters:\n") + print(format(object$clusters, digits=digits), print.gap=2L, quote=FALSE) + + cat("\n") + for(i in 1:length(object$signals)){ + cat("Cluster",i,":\n") + print(format(object$signals[[i]], digits=digits), print.gap=2L, quote=FALSE) + cat("\n") + } + + }else{ + cat("\nNo Independent Association Signal Clusters.\n") + } + + cat("Please refer to $variant for PIP of top predictors,\n") + cat(" and model.dap() for configuration of top models.\n") + + cat("\n") + invisible(object) +} + + +#' Integrative Genetic Association Analysis using Deterministic Approximation of Posteriors for SBAMS-format Data +#' +#' \code{dap.sbams} is an interface built especially for SBAMS-format files, which is designed to perform rigorous enrichment analysis, QTL discovery and multi-SNP fine-mapping analysis in a highly efficient way. +#' +#' @aliases dap.sbams +#' @param file file path to a sbams file +#' @param prior (optional) a \code{data.frame} with 1st column as snp names, and 2nd column as prior probabilities. If any snp in the input file is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in the input file. +#' @param ens (optional) prior expected number of signals, \code{ens=1} by default. +#' @param pi1 (optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output. +#' @param size_limit (optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation. +#' @param thread (optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option. +#' @param quiet (optional) If TRUE, dap will mute running logs. +#' @return \code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +#' \item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +#' \item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +#' \item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +#' \item{model.summary}{a list of information on candidate models:\describe{ +#' \item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +#' \item{model.size}{information on expected model size and corresponding standard deviation.} +#' \item{log10NC}{log10 normalizing constant.} +#' \item{PIP.min}{the minimum posterior inclusion probability.} +#' \item{N}{the sample size.} +#' \item{response}{the name of the phenotype/response variable.}}} +#' \item{call}{the matched call.} +#' @details Please refer to \url{https://github.com/xqwen/dap/tree/master/dap_src} for more details. +#' @seealso Please see \code{\link{summary.dap}} for summaries; and \code{\link{read.sbams}} for reading in sbams-format files as an \R \code{data frame} which can call the general version of \code{\link{dap}} function. +#' @references Wen, X., Lee, Y., Luca, F., Pique-Regi, R. Efficient Integrative Multi-SNP Association Analysis using Deterministic Approximation of Posteriors. \emph{The American Journal of Human Genetics}, 98(6), 1114--1129 +#' @references Lee, Y, Luca, F, Pique-Regi, R,Wen, X. Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics bioRxiv:316471 +#' @examples +#' sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +#' test.dap.sbams = dap.sbams(sbams.file) +#' test.dap.sbams +#' +#' summary(test.dap.sbams) +#' +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +dap.sbams <- function(file, prior=NULL, ens=1, pi1=-1, ld_control=0.25, msize=-1, converg_thresh=0.01, all=FALSE, size_limit=-1, thread=1, quiet=FALSE) +{ + cl = match.call() + params = list(data=file) + + if(!is.null(prior)){ + if(class(prior)=="data.frame"){ + if(nrow(prior)>0 & ncol(prior)>1){ + params$has_prior = TRUE + params$prior_snp_names = prior[,1] + params$prior_values = prior[,2] + } + } + } + + if(class(ens)=="numeric" & ens > 0) params$ens=ens + if(class(pi1)=="numeric" & pi1>0 & pi1<1) params$pi1=pi1 + if(class(ld_control)=="numeric" & ld_control>=0 & ld_control<1) params$ld_control=ld_control + if(class(msize)=="numeric" & as.integer(msize) >= 1) params$msize=as.integer(msize) + if(class(converg_thresh)=="numeric" & converg_thresh>=0) params$converg_thresh=converg_thresh + if(class(all)=="logical" & all) params$all=1 + if(class(size_limit)=="numeric" & size_limit>=1) params$size_limit=size_limit + if(class(thread)=="numeric" & as.integer(thread)>1) params$t=as.integer(thread) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap', 1, params, as.numeric(quiet)) + + result$call = cl + result$model.summary$model$configuration = gsub("&", "+", result$model.summary$model$configuration) + class(result) = "dap" + return(result) +} + +#' @export +model.dap = function(object) +{ + if(!inherits(object, "dap")) + warning("calling model.dap() ...") + return(object$model.summary$model) +} + +#' Structured Bayesian Model Selection via Deterministic Approximation of Posteriors using Sufficient Summary Statistics +#' +#' The sufficient summary statistics refer to the following information: \itemize{ +#' \item estimated effect size and corresponding estimated standard error from single SNP testing for each SNP +#' \item correlation matrix of SNPs +#' \item sample size +#' \item total sum of squares for the quantitative phenotype +#' } +#' Note that the using sufficient summary statistics yield the same results (except small numerical difference) as that using individual-level data. +#' +#' @param est a data.frame or matrix with 3 columns representing SNP names, effect size estimates and corresponding standard errors respectively. +#' @param ld a data.frame or matrix containing the correlation matrix between SNPs. The order of the SNP is required to match the order listed in \code{est}. +#' @param n an integer that specifies the sample size. +#' @param syy the total sum of squares for the quantitative phenotype. +#' @param pheno_name (optional) the name of the phenotype. For display use and follow-up TWAS analysis only. +#' @param prior (optional) a \code{data.frame} with 1st column as SNP names, and 2nd column as prior probabilities. If any snp in \code{est} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{est}. +#' @param ens (optional) prior expected number of signals, \code{ens=1} by default. +#' @param pi1 (optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output. +#' @param size_limit (optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation. +#' @param thread (optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option. +#' @param quiet (optional) If TRUE, dap will mute running logs. +#' @return \code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +#' \item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +#' \item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +#' \item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +#' \item{model.summary}{a list of information on candidate models:\describe{ +#' \item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +#' \item{model.size}{information on expected model size and corresponding standard deviation.} +#' \item{log10NC}{log10 normalizing constant.} +#' \item{PIP.min}{the minimum posterior inclusion probability.} +#' \item{N}{the sample size.} +#' \item{response}{the name of the phenotype/response variable.}}} +#' \item{call}{the matched call.} +#' +#' @seealso Please see \code{\link{extract.sbams}} for obtaining sufficient summary statistics from a sbams file. +#' +#' @examples +#' est_file = system.file("sbamsdat", "sim.1.est.dat", package = "dap") +#' ld_file = system.file("sbamsdat", "sim.1.ld.dat", package = "dap") +#' est = read.table(est_file) +#' ld = read.table(ld_file) +#' ld = as.matrix(ld) +#' dap.ss(est, ld, 343, 515.6, pheno_name="gene") +#' +#' # It should yield the same result as: +#' sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +#' dap.sbams(sbams.file) +#' +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +dap.ss = function(est, ld, n, syy, pheno_name="", prior=NULL, ens=1, pi1=-1, ld_control=0.25, msize=-1, converg_thresh=0.01, all=FALSE, size_limit=-1, thread=1, quiet=FALSE){ + cl = match.call() + ld = as.matrix(ld) + params = list(snp_names=est[,1], beta=est[,2], se=est[,3], ld=ld, n=n, syy=syy, pheno_name=pheno_name) + + if(!is.null(prior)){ + if(class(prior)=="data.frame"){ + if(nrow(prior)>0 & ncol(prior)>1){ + params$has_prior = TRUE + params$prior_snp_names = prior[,1] + params$prior_values = prior[,2] + } + } + } + + if(class(ens)=="numeric" & ens > 0) params$ens=ens + if(class(pi1)=="numeric" & pi1>0 & pi1<1) params$pi1=pi1 + if(class(ld_control)=="numeric" & ld_control>=0 & ld_control<1) params$ld_control=ld_control + if(class(msize)=="numeric" & as.integer(msize) >= 1) params$msize=as.integer(msize) + if(class(converg_thresh)=="numeric" & converg_thresh>=0) params$converg_thresh=converg_thresh + if(class(all)=="logical" & all) params$all=1 + if(class(size_limit)=="numeric" & size_limit>=1) params$size_limit=size_limit + if(class(thread)=="numeric" & as.integer(thread)>1) params$t=as.integer(thread) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap', 3, params, as.numeric(quiet)) + result$model.summary$model$configuration = gsub("&", "+", result$model.summary$model$configuration) + result$call = cl + class(result) = "dap" + return(result) +} + +#' Structured Bayesian Model Selection via Deterministic Approximation of Posteriors using Z-Scores and LD Information +#' +#' \code{dap.z} accepts input in the format of z-scores (from single-SNP testing) and LD matrix. Note the results are typically more conservative than that from \code{dap} using individual-level data or \code{dap.ss} using sufficient statistics. +#' +#' @param z a data.frame or matrix with 2 columns representing SNP names and corresponding z-scores respectively. +#' @param ld a data.frame or matrix containing the correlation matrix between SNPs. The order of the SNP is required to match the order listed in \code{est}. +#' @param n (optional) an integer that specifies the (approximate) sample size which is used to estimate the input z-scores, 1000 by default. +#' @param pheno_name (optional) the name of the phenotype. For display use and follow-up TWAS analysis only. +#' @param prior (optional) a \code{data.frame} with 1st column as SNP names, and 2nd column as prior probabilities. If any snp in \code{z} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{z}. +#' @param ens (optional) prior expected number of signals, \code{ens=1} by default. +#' @param pi1 (optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output. +#' @param size_limit (optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation. +#' @param thread (optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option. +#' @param quiet (optional) If TRUE, dap will mute running logs. +#' @return \code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +#' \item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +#' \item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +#' \item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +#' \item{model.summary}{a list of information on candidate models:\describe{ +#' \item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +#' \item{model.size}{information on expected model size and corresponding standard deviation.} +#' \item{log10NC}{log10 normalizing constant.} +#' \item{PIP.min}{the minimum posterior inclusion probability.} +#' \item{N}{the sample size.} +#' \item{response}{the name of the phenotype/response variable.}}} +#' \item{call}{the matched call.} +#' @examples +#' z_file = system.file("sbamsdat", "sim.1.zval.dat", package = "dap") +#' ld_file = system.file("sbamsdat", "sim.1.ld.dat", package = "dap") +#' zscores = read.table(z_file) +#' ld = read.table(ld_file) +#' dap.z(zscores, ld, n=343, pheno_name="gene") +#' +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +dap.z = function(z, ld, n=1000, pheno_name="", prior=NULL, ens=1, pi1=-1, ld_control=0.25, msize=-1, converg_thresh=0.01, all=FALSE, size_limit=-1, thread=1, quiet=FALSE){ + cl = match.call() + ld = as.matrix(ld) + params = list(snp_names=z[,1], zvals=z[,2], ld=ld, n=n, pheno_name=pheno_name) + + if(!is.null(prior)){ + if(class(prior)=="data.frame"){ + if(nrow(prior)>0 & ncol(prior)>1){ + params$has_prior = TRUE + params$prior_snp_names = prior[,1] + params$prior_values = prior[,2] + } + } + } + + if(class(ens)=="numeric" & ens > 0) params$ens=ens + if(class(pi1)=="numeric" & pi1>0 & pi1<1) params$pi1=pi1 + if(class(ld_control)=="numeric" & ld_control>=0 & ld_control<1) params$ld_control=ld_control + if(class(msize)=="numeric" & as.integer(msize) >= 1) params$msize=as.integer(msize) + if(class(converg_thresh)=="numeric" & converg_thresh>=0) params$converg_thresh=converg_thresh + if(class(all)=="logical" & all) params$all=1 + if(class(size_limit)=="numeric" & size_limit>=1) params$size_limit=size_limit + if(class(thread)=="numeric" & as.integer(thread)>1) params$t=as.integer(thread) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap', 4, params, as.numeric(quiet)) + result$model.summary$model$configuration = gsub("&", "+", result$model.summary$model$configuration) + result$call = cl + class(result) = "dap" + return(result) +} + diff --git a/dap_src/R-package/R/sbams.R b/dap_src/R-package/R/sbams.R new file mode 100644 index 0000000..b943501 --- /dev/null +++ b/dap_src/R-package/R/sbams.R @@ -0,0 +1,55 @@ +#' Read a sbams file +#' +#' This function will import the sbams file, automatically impute missing values with mean, regress pheno and geno out of controlled covariants if applicable, and generate an \R data frame which can be passed into the \code{\link{dap}} function. +#' +#' @param file file path to the sbams file +#' @return a data.frame with the first colunm as the normalized phenotype, and the following columns as the normalized genotypes. +#' @details Please refer to \url{https://github.com/xqwen/dap/tree/master/dap_src} for more details. +#' @examples +#' sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +#' sbams.dat = read.sbams(sbams.file) +#' test.dap.sbams.dat = dap(gene~., sbams.dat) +#' +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +read.sbams <- function(file) { + result = .Call(`_dap_read_sbams`, PACKAGE = 'dap', file) + return(result) +} + +#' Extract Sufficient Statistics from a sbams file +#' +#' The sufficient summary statistics refer to the following information: \itemize{ +#' \item estimated effect size and corresponding estimated standard error from single SNP testing for each SNP +#' \item correlation matrix of SNPs +#' \item sample size +#' \item total sum of squares for the quantitative phenotype +#' } +#' +#' @param file file path to the sbams file +#' @param ens (optional) prior expected number of signals, \code{ens=1} by default. +#' @param pi1 (optional) the exchangeable prior probability, values \code{0 0) params$ens=ens + if(class(pi1)=="numeric" & pi1>0 & pi1<1) params$pi1=pi1 + + result = .Call(`_dap_extract_sbams`, PACKAGE = 'dap', params) + return(result) +} + diff --git a/dap_src/R-package/R/scan.R b/dap_src/R-package/R/scan.R new file mode 100644 index 0000000..f39e8db --- /dev/null +++ b/dap_src/R-package/R/scan.R @@ -0,0 +1,89 @@ +#' Single-SNP Association Analysis +#' +#' \code{scan} is used perform perform single-SNP fine-mapping analysis. +#' +#' @usage +#' scan(formula, data) +#' +#' @aliases scan +#' @param formula an object of class \code{formula} (or one that can be coerced to that class): a symbolic description of the model to be fitted. +#' @param data a data frame containing the variables in the model. +#' @return \code{scan} returns a \code{data.frame} containing effect estimates for each single SNP. +#' @examples +#' set.seed(0) +#' n = 100 +#' p = 1000 +#' +#' a1 = rnorm(n) +#' a2 = 10*a1+rnorm(n) +#' a3 = 2*a1+9*a2+rnorm(n) +#' +#' b1 = rnorm(n) +#' b2 = 8*b1+rnorm(n) +#' +#' x = matrix(rnorm(n*(p-5)), nrow=n) +#' +#' df = data.frame(a1,a2,a3,b1,b2,x) +#' df$y = 2*a1+b1+rnorm(n) +#' +#' test.scan = scan(y~., df) +#' head(test.scan) +#' +#' @seealso \code{\link{scan.sbams}} for a different interface directly analyzing a sbams-format file. +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +scan = function(formula, data){ + cl = match.call() + mf = match.call(expand.dots = FALSE) + m <- match(c("formula", "data"), names(mf), 0L) + mf <- mf[c(1L, m)] + mf$drop.unused.levels <- TRUE + mf[[1L]] <- quote(stats::model.frame) + mf <- eval(mf, parent.frame()) + mt <- attr(mf, "terms") + + y = model.response(mf, "numeric") + attr(mt, "intercept") = 0 + x <- model.matrix(mt, mf) + + # impute with mean + y[is.na(y)] = mean(y, na.rm = TRUE) + x = apply(x, 2, function(t) replace(t, is.na(t), mean(t, na.rm=TRUE))) + + params = list(x=x,y=y,pheno_name=all.vars(cl)[1],scan=TRUE) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap', 2, params, 1) + + return(result[[1]]) +} + +#' Single-SNP Association Analysis for SBAMS-format Data +#' +#' \code{scan.sbams} is an interface built especially for SBAMS-format files, which is designed to perform single-SNP fine-mapping analysis. +#' +#' @usage +#' scan.sbams(file) +#' +#' @aliases scan.sbams +#' @param file file path to a sbams file +#' @return \code{scan.sbams} returns a \code{data.frame} containing effect estimates for each single SNP. +#' @examples \dontrun{ +#' +#' sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +#' test.scan.sbams = scan.sbams(sbams.file) +#' head(test.scan.sbams) +#' +#' } +#' @seealso \code{\link{read.sbams}} for reading in sbams-format files as an \R \code{data.frame} which can call the general version of \code{\link{scan}} function. +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +scan.sbams <- function(file) +{ + params = list(data=file, scan=TRUE) + + result = .Call(`_dap_dap_main`, PACKAGE = 'dap', 1, params, 1) + + return(result[[1]]) +} diff --git a/dap_src/R-package/R/twas.R b/dap_src/R-package/R/twas.R new file mode 100644 index 0000000..b3a9b8d --- /dev/null +++ b/dap_src/R-package/R/twas.R @@ -0,0 +1,78 @@ +#' TWAS Builder +#' +#' \code{twas} calculates weights on variants. +#' +#' @usage +#' twas(data, dap) +#' +#' @aliases twas +#' @param data a data frame containing the variables in the model. +#' @param dap a dap object +#' @return \code{twas} returns an object of \code{"twas"}, which is a list containing the following components: +#' \item{weight}{a data frame of variants and corresponding weights.} +#' \item{ER2}{the expected R-squared.} +#' @examples +#' set.seed(0) +#' n = 100 +#' p = 1000 +#' +#' a1 = rnorm(n) +#' a2 = 10*a1+rnorm(n) +#' a3 = 2*a1+9*a2+rnorm(n) +#' +#' b1 = rnorm(n) +#' b2 = 8*b1+rnorm(n) +#' +#' x = matrix(rnorm(n*(p-5)), nrow=n) +#' +#' df = data.frame(a1,a2,a3,b1,b2,x) +#' df$y = 2*a1+b1+rnorm(n) +#' +#' test.dap = dap(y~., df) +#' twas(df, test.dap) +#' +#' @useDynLib dap, .registration = TRUE +#' @importFrom Rcpp sourceCpp +#' @export +twas = function(data, dap){ + + # sanity check + cl = match.call() + if(class(data)!="data.frame") stop(paste(deparse(cl$data),"is not a data.frame!")) + if(class(dap) !="dap") stop(paste(deparse(cl$dap)), "is not a dap object!") + if(dap$model.summary$N != nrow(data)) warning(paste("The number of samples in", deparse(cl$data), "does not match that in", deparse(cl$dap),"!")) + if(!(dap$model.summary$response %in% names(data))) stop(paste("The response variable", dap$model.summary$response, "is not found in", deparse(cl$data))) + + models = dap$model.summary$model[dap$model.summary$model$size>0,] + vars = unique(unlist(sapply(models$configuration, function(x) strsplit(x,"\\+")))) + vars_not_in = !(vars%in% names(data)) + if(sum(vars_not_in) > 0) stop(paste(paste(vars[vars_not_in], collapse=","), "NOT found in", deparse(cl$data))) + + X = data[,vars] + y = data[,dap$model.summary$response] + + # impute with mean + y[is.na(y)] = mean(y, na.rm = TRUE) + X = apply(X, 2, function(t) replace(t, is.na(t), mean(t, na.rm=TRUE))) + + ymean = mean(y) + const = sum((y-ymean)^2) + coefs = rep(0, length(vars)) + names(coefs) = vars + ER2 = 0 + + for(i in 1:nrow(models)){ + this_vars = strsplit(models$configuration[i],"\\+")[[1]] + this_result = lm.fit(cbind(1,as.matrix(X[,this_vars])),y) + this_weight = models$posterior[i] + coefs[names(this_result$coef[-1])] = coefs[names(this_result$coef[-1])]+this_result$coef[-1]*this_weight + ER2 = ER2 + this_weight*(1-sum(this_result$residuals^2)/const) + } + + index_sorted = sort(abs(coefs), decreasing = TRUE, index.return=TRUE)$ix + twas_df = data.frame(predictor=names(coefs), weight = coefs)[index_sorted,] + row.names(twas_df) = 1:length(coefs) + result = list(weights=twas_df, ER2=ER2) + class(result) = "twas" + return(result) +} diff --git a/dap_src/R-package/README.md b/dap_src/R-package/README.md new file mode 100644 index 0000000..b1eccd7 --- /dev/null +++ b/dap_src/R-package/README.md @@ -0,0 +1,179 @@ +dap: An R package for Bayesian model selection via DAP +====================================================== + +This package is designed for structured Bayesian model selection via adaptive deterministic approximation of posteriors (DAP) algorithm. Applications include genetic association analysis integrating genomic annotations. These methods are designed to perform rigorous enrichment analysis, QTL discovery and multi-SNP fine-mapping analysis in a highly efficient way. + +Installation +------------ + +Pre-installation of [GNU Scientific Library (GSL)](https://www.gnu.org/software/gsl/) is required, and [OpenMP](https://www.openmp.org) compatible compiler is recommended. + +`dap` has not been released on CRAN yet. It can be installed as follows in an R session: + +``` r +devtools::install_github("https://github.com/yukt/dap.git", ref="rpackage", subdir = "dap_src/R-package") +``` + +Once installed, the package can be loaded in a given R session using: + +``` r +library(dap) +help(dap) # for detailed documentation +``` + +Analysis Examples +----------------- + +To illustrate how the package works, we create a toy dataset `df`. It consists of a response variable `y` and 1000 candidate predictors, in which only `a1` and `b1` are causal. `a2` and `a3` are highly correlated with `a1`, `b2` is highly correlated with `b1`, and `x1`-`x995` are unrelated to `y`. + +``` r +set.seed(0) +n = 100 +p = 1000 + +a1 = rnorm(n) +a2 = 10*a1+rnorm(n) +a3 = 2*a1+9*a2+rnorm(n) + +b1 = rnorm(n) +b2 = 8*b1+rnorm(n) + +x = matrix(rnorm(n*(p-5)), nrow=n) + +df = data.frame(a1,a2,a3,b1,b2,x) +df$y = 2*a1+b1+rnorm(n) +``` + +To perform variable selection, we run the analysis as follows. It will print out the configuration of dap model while running, and the return is a `dap` object. + +``` r +test.dap = dap(y~., df) +``` + + ## + ## ============ DAP Configuration ============ + ## + ## INPUT + ## + ## * individual-level data + ## * number of candidate predictors: 1000 + ## * sample size: 100 + ## + ## PROGRAM OPTIONS + ## + ## * maximum model size allowed [ msize = 1000 ] (no restriction) + ## * LD control threshold [ ld_control = 0.25 ] + ## * normalizing constant convergence threshold [ converg_thresh = 1.00e-02 ] (log10 scale) + ## * number of parallel threads [ thread = 1 ] (OpenMP not available) + ## + ## =========================================== + +To see the analysis result by typing the `dap` object name: + +``` r +test.dap +``` + + ## + ## Call: + ## dap(formula = y ~ ., data = df) + ## + ## Posterior expected model size: 2.025 ( sd = 0.1615 ) + ## LogNC = 63.05 ( Log10NC = 27.38 ) + ## Minimum PIP is estimated at 0.0001001 ( N = 100 ) + ## + ## Independent Association Signal Clusters: + ## cluster.size cluster.pip average.r2 member.predictors + ## 1 3 0.9999 0.9925 a1 a2 a3 + ## 2 2 0.9999 0.9802 b1 b2 + ## + ## One of the best models is: + ## y ~ a1 + b1 + ## + ## Please refer to $signal for PIP of top predictors, + ## and $model for configuration of top models. + +According to the result, the analysis reveals 2 signal cluster `{a1, a2, a3}` and `{b1, b2}` with high posterior inclusion probability (PIP), as desired. It also suggests one model configuration `y ~ a1 + b1`. To see information on other plausible model configurations, and details about the predictors within each signal clusters, we can use the `summary` function: + +``` r +summary(test.dap) +``` + + ## + ## Call: + ## dap(formula = y ~ ., data = df) + ## + ## Posterior expected model size: 2.0251 ( sd = 0.16153 ) + ## LogNC = 63.047 ( Log10NC = 27.381 ) + ## Minimum PIP is estimated at 0.0001001 ( N = 100 ) + ## + ## Top Models: + ## model size posterior score + ## 1 a1 + b1 2 0.558895 27.128 + ## 2 a1 + b2 2 0.309274 26.871 + ## 3 a2 + b2 2 0.076997 26.267 + ## 4 a1 + b1 + X969 3 0.015755 25.578 + ## 5 a2 + b1 2 0.015651 25.576 + ## + ## + ## Independent Association Signal Clusters: + ## cluster.size cluster.pip r2 matrix + ## 1 3 0.99989 0.992522 0.024257 + ## 2 2 0.99989 0.024257 0.980151 + ## + ## Cluster 1 : + ## predictor pip log10abf + ## 1 a1 0.891022 22.969 + ## 2 a2 0.094350 22.055 + ## 3 a3 0.014513 21.231 + ## + ## Cluster 2 : + ## predictor pip log10abf + ## 1 b1 0.59091 4.8043 + ## 2 b2 0.40897 4.9174 + ## + ## Please refer to $signal for PIP of top predictors, + ## and $model for configuration of top models. + +### SBAMS-Format File Support + +The sbams format is designed for to represent data from a meta-analytic setting including data from multiple subgroups. The file contains a phenotype section and a genotype section. This package implements an interface `read.sbams` which reading the sbams-format file into a standard R data.frame, which can be seamlessly passed into the `dap` function: + +``` r +sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +sbams.dat = read.sbams(sbams.file) +test.dap.sbams.1 = dap(gene~., sbams.dat, quiet=TRUE) +``` + +Also, we implement a function `dap.sbams` which can directly read and analyze the sbams-format file. + +``` r +test.dap.sbams.2 = dap.sbams(sbams.file, quiet=TRUE) +``` + +Citation +-------- + +``` r +citation("dap") +``` + + ## + ## To cite dap in publications use: + ## + ## Wen, X., Lee, Y., Luca, F., & Pique-Regi, R. (2016). Efficient + ## integrative multi-SNP association analysis via deterministic + ## approximation of posteriors. The American Journal of Human + ## Genetics, 98(6), 1114-1129. + ## https://doi.org/10.1016/j.ajhg.2016.03.029 + ## + ## Lee, Y., Francesca, L., Pique-Regi, R., & Wen, X. (2018). + ## Bayesian Multi-SNP Genetic Association Analysis: Control of FDR + ## and Use of Summary Statistics. bioRxiv, 316471. + ## https://doi.org/10.1101/316471 + ## + ## To see these entries in BibTeX format, use 'print(, + ## bibtex=TRUE)', 'toBibtex(.)', or set + ## 'options(citation.bibtex.max=999)'. + +You can get citation information in BibTeX format via `print(citation("dap"), bibtex=TRUE)`. diff --git a/dap_src/R-package/inst/CITATION b/dap_src/R-package/inst/CITATION new file mode 100644 index 0000000..9259b0c --- /dev/null +++ b/dap_src/R-package/inst/CITATION @@ -0,0 +1,39 @@ +citHeader("To cite dap in publications use:") + +citEntry(entry = "Article", + title = "Efficient integrative multi-SNP association analysis via deterministic approximation of posteriors", + author = personList(as.person("Xiaoquan Wen"), + as.person("Yeji Lee"), + as.person("Francesca Luca"), + as.person("Roger Pique-Regi")), + journal = "The American Journal of Human Genetics", + year = "2016", + volume = "98", + number = "6", + pages = "1114--1129", + url = "https://doi.org/10.1016/j.ajhg.2016.03.029", + + textVersion = + paste("Wen, X., Lee, Y., Luca, F., & Pique-Regi, R. (2016).", + "Efficient integrative multi-SNP association analysis via deterministic approximation of posteriors.", + "The American Journal of Human Genetics, 98(6), 1114-1129.", + "https://doi.org/10.1016/j.ajhg.2016.03.029") +) + +citEntry(entry = "Article", + title = "Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics", + author = personList(as.person("Yeji Lee"), + as.person("Francesca Luca"), + as.person("Roger Pique-Regi"), + as.person("Xiaoquan Wen")), + journal = "bioRxiv", + year = "2018", + pages = "316471", + url = "https://doi.org/10.1101/316471", + + textVersion = + paste("Lee, Y., Francesca, L., Pique-Regi, R., & Wen, X. (2018).", + "Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics.", + "bioRxiv, 316471.", + "https://doi.org/10.1101/316471") +) \ No newline at end of file diff --git a/dap_src/R-package/inst/sbamsdat/sim.1.LD.dat b/dap_src/R-package/inst/sbamsdat/sim.1.LD.dat new file mode 100644 index 0000000..bb7f5aa --- /dev/null +++ b/dap_src/R-package/inst/sbamsdat/sim.1.LD.dat @@ -0,0 +1,1001 @@ +1.000000 -0.163153 -0.159005 0.503536 -0.234519 0.066098 -0.137667 0.806536 0.251319 0.217265 0.785767 -0.003403 0.003847 -0.010688 -0.014278 0.003847 0.003847 0.003847 0.003847 0.003847 0.010109 0.003847 0.043636 -0.093574 0.007988 0.007988 0.007988 -0.052640 -0.000948 -0.001087 0.026340 0.064065 -0.050107 0.048603 0.096858 -0.009337 0.044921 -0.006490 0.018365 0.049926 0.048181 0.002495 0.018035 -0.004914 -0.058664 -0.074993 -0.068615 -0.068615 -0.061822 -0.048394 -0.064299 -0.060494 0.064299 -0.044462 0.047088 0.073295 0.031248 0.077119 0.008680 0.075268 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coerced to that class): a symbolic description of the model to be fitted.} + +\item{data}{a \code{data.frame} containing the variables in the model.} + +\item{prior}{(optional) a \code{data.frame} with 1st column as snp names, and 2nd column as prior probabilities. If any snp in \code{data} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{data}.} + +\item{ens}{(optional) prior expected number of signals, \code{ens=1} by default.} + +\item{pi1}{(optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output.} + +\item{size_limit}{(optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation.} + +\item{thread}{(optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option.} + +\item{quiet}{(optional) If TRUE, dap will mute running logs.} +} +\value{ +\code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +\item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +\item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +\item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +\item{model.summary}{a list of information on candidate models:\describe{ +\item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +\item{model.size}{information on expected model size and corresponding standard deviation.} +\item{log10NC}{log10 normalizing constant.} +\item{PIP.min}{the minimum posterior inclusion probability.} +\item{N}{the sample size.} +\item{response}{the name of the phenotype/response variable.}}} +\item{call}{the matched call.} +} +\description{ +\code{dap} is used perform Bayesian variable selection among a large scale of predictors, multicolinearty and missingness are allowed. It will automatically impute missingness in the input data with mean values, normalize the response and predictors, and propose top predictive signals and signal clusters according to posterior probability. +} +\details{ +Please refer to \url{https://github.com/xqwen/dap/tree/master/dap_src} for more details. +} +\examples{ +set.seed(0) +n = 100 +p = 1000 + +a1 = rnorm(n) +a2 = 10*a1+rnorm(n) +a3 = 2*a1+9*a2+rnorm(n) + +b1 = rnorm(n) +b2 = 8*b1+rnorm(n) + +x = matrix(rnorm(n*(p-5)), nrow=n) + +df = data.frame(a1,a2,a3,b1,b2,x) +df$y = 2*a1+b1+rnorm(n) + +test.dap = dap(y~., df) +test.dap + +summary(test.dap) + + +### example with prior #### +prior = data.frame(snp=c("a1","b1"), prior=c(0.5,0.5)) +dap(y~., df, prior=prior) + +} +\references{ +Wen, X., Lee, Y., Luca, F., Pique-Regi, R. Efficient Integrative Multi-SNP Association Analysis using Deterministic Approximation of Posteriors. \emph{The American Journal of Human Genetics}, 98(6), 1114--1129 + +Lee, Y, Luca, F, Pique-Regi, R,Wen, X. Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics bioRxiv:316471 +} +\seealso{ +Please see \code{\link{summary.dap}} for summaries; and \code{\link{dap.sbams}} for a different interface directly analyzing a sbams-format file. +} diff --git a/dap_src/R-package/man/dap.sbams.Rd b/dap_src/R-package/man/dap.sbams.Rd new file mode 100644 index 0000000..96b180d --- /dev/null +++ b/dap_src/R-package/man/dap.sbams.Rd @@ -0,0 +1,69 @@ +% Generated by roxygen2: do not edit by hand +% Please edit documentation in R/main.R +\name{dap.sbams} +\alias{dap.sbams} +\title{Integrative Genetic Association Analysis using Deterministic Approximation of Posteriors for SBAMS-format Data} +\usage{ +dap.sbams(file, prior = NULL, ens = 1, pi1 = -1, ld_control = 0.25, + msize = -1, converg_thresh = 0.01, all = FALSE, size_limit = -1, + thread = 1, quiet = FALSE) +} +\arguments{ +\item{file}{file path to a sbams file} + +\item{prior}{(optional) a \code{data.frame} with 1st column as snp names, and 2nd column as prior probabilities. If any snp in the input file is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in the input file.} + +\item{ens}{(optional) prior expected number of signals, \code{ens=1} by default.} + +\item{pi1}{(optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output.} + +\item{size_limit}{(optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation.} + +\item{thread}{(optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option.} + +\item{quiet}{(optional) If TRUE, dap will mute running logs.} +} +\value{ +\code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +\item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +\item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +\item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +\item{model.summary}{a list of information on candidate models:\describe{ +\item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +\item{model.size}{information on expected model size and corresponding standard deviation.} +\item{log10NC}{log10 normalizing constant.} +\item{PIP.min}{the minimum posterior inclusion probability.} +\item{N}{the sample size.} +\item{response}{the name of the phenotype/response variable.}}} +\item{call}{the matched call.} +} +\description{ +\code{dap.sbams} is an interface built especially for SBAMS-format files, which is designed to perform rigorous enrichment analysis, QTL discovery and multi-SNP fine-mapping analysis in a highly efficient way. +} +\details{ +Please refer to \url{https://github.com/xqwen/dap/tree/master/dap_src} for more details. +} +\examples{ +sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +test.dap.sbams = dap.sbams(sbams.file) +test.dap.sbams + +summary(test.dap.sbams) + +} +\references{ +Wen, X., Lee, Y., Luca, F., Pique-Regi, R. Efficient Integrative Multi-SNP Association Analysis using Deterministic Approximation of Posteriors. \emph{The American Journal of Human Genetics}, 98(6), 1114--1129 + +Lee, Y, Luca, F, Pique-Regi, R,Wen, X. Bayesian Multi-SNP Genetic Association Analysis: Control of FDR and Use of Summary Statistics bioRxiv:316471 +} +\seealso{ +Please see \code{\link{summary.dap}} for summaries; and \code{\link{read.sbams}} for reading in sbams-format files as an \R \code{data frame} which can call the general version of \code{\link{dap}} function. +} diff --git a/dap_src/R-package/man/dap.ss.Rd b/dap_src/R-package/man/dap.ss.Rd new file mode 100644 index 0000000..8d3a03f --- /dev/null +++ b/dap_src/R-package/man/dap.ss.Rd @@ -0,0 +1,80 @@ +% Generated by roxygen2: do not edit by hand +% Please edit documentation in R/main.R +\name{dap.ss} +\alias{dap.ss} +\title{Structured Bayesian Model Selection via Deterministic Approximation of Posteriors using Sufficient Summary Statistics} +\usage{ +dap.ss(est, ld, n, syy, pheno_name = "", prior = NULL, ens = 1, + pi1 = -1, ld_control = 0.25, msize = -1, converg_thresh = 0.01, + all = FALSE, size_limit = -1, thread = 1, quiet = FALSE) +} +\arguments{ +\item{est}{a data.frame or matrix with 3 columns representing SNP names, effect size estimates and corresponding standard errors respectively.} + +\item{ld}{a data.frame or matrix containing the correlation matrix between SNPs. The order of the SNP is required to match the order listed in \code{est}.} + +\item{n}{an integer that specifies the sample size.} + +\item{syy}{the total sum of squares for the quantitative phenotype.} + +\item{pheno_name}{(optional) the name of the phenotype. For display use and follow-up TWAS analysis only.} + +\item{prior}{(optional) a \code{data.frame} with 1st column as SNP names, and 2nd column as prior probabilities. If any snp in \code{est} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{est}.} + +\item{ens}{(optional) prior expected number of signals, \code{ens=1} by default.} + +\item{pi1}{(optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output.} + +\item{size_limit}{(optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation.} + +\item{thread}{(optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option.} + +\item{quiet}{(optional) If TRUE, dap will mute running logs.} +} +\value{ +\code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +\item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +\item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +\item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +\item{model.summary}{a list of information on candidate models:\describe{ +\item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +\item{model.size}{information on expected model size and corresponding standard deviation.} +\item{log10NC}{log10 normalizing constant.} +\item{PIP.min}{the minimum posterior inclusion probability.} +\item{N}{the sample size.} +\item{response}{the name of the phenotype/response variable.}}} +\item{call}{the matched call.} +} +\description{ +The sufficient summary statistics refer to the following information: \itemize{ +\item estimated effect size and corresponding estimated standard error from single SNP testing for each SNP +\item correlation matrix of SNPs +\item sample size +\item total sum of squares for the quantitative phenotype +} +Note that the using sufficient summary statistics yield the same results (except small numerical difference) as that using individual-level data. +} +\examples{ +est_file = system.file("sbamsdat", "sim.1.est.dat", package = "dap") +ld_file = system.file("sbamsdat", "sim.1.ld.dat", package = "dap") +est = read.table(est_file) +ld = read.table(ld_file) +ld = as.matrix(ld) +dap.ss(est, ld, 343, 515.6, pheno_name="gene") + +# It should yield the same result as: +sbams.file = system.file("sbamsdat", "sim.1.sbams.dat", package = "dap") +dap.sbams(sbams.file) + +} +\seealso{ +Please see \code{\link{extract.sbams}} for obtaining sufficient summary statistics from a sbams file. +} diff --git a/dap_src/R-package/man/dap.z.Rd b/dap_src/R-package/man/dap.z.Rd new file mode 100644 index 0000000..96d4f4b --- /dev/null +++ b/dap_src/R-package/man/dap.z.Rd @@ -0,0 +1,64 @@ +% Generated by roxygen2: do not edit by hand +% Please edit documentation in R/main.R +\name{dap.z} +\alias{dap.z} +\title{Structured Bayesian Model Selection via Deterministic Approximation of Posteriors using Z-Scores and LD Information} +\usage{ +dap.z(z, ld, n = 1000, pheno_name = "", prior = NULL, ens = 1, + pi1 = -1, ld_control = 0.25, msize = -1, converg_thresh = 0.01, + all = FALSE, size_limit = -1, thread = 1, quiet = FALSE) +} +\arguments{ +\item{z}{a data.frame or matrix with 2 columns representing SNP names and corresponding z-scores respectively.} + +\item{ld}{a data.frame or matrix containing the correlation matrix between SNPs. The order of the SNP is required to match the order listed in \code{est}.} + +\item{n}{(optional) an integer that specifies the (approximate) sample size which is used to estimate the input z-scores, 1000 by default.} + +\item{pheno_name}{(optional) the name of the phenotype. For display use and follow-up TWAS analysis only.} + +\item{prior}{(optional) a \code{data.frame} with 1st column as SNP names, and 2nd column as prior probabilities. If any snp in \code{z} is not found in this data frame, the corresponding prior will be set as \code{ens/p}, where \code{p} is number of SNPs in \code{z}.} + +\item{ens}{(optional) prior expected number of signals, \code{ens=1} by default.} + +\item{pi1}{(optional) the exchangeable prior probability, values \code{0 0.001} and signal clusters with \code{SPIP > 0.25} are output.} + +\item{size_limit}{(optional) the maximum number of predictors allowed in a signal cluster. By default -1, there is no constraint and the size of each signal cluster is completely data determined. Setting a small number forces DAP to cap the number of predictors into each cluster and reduces computation.} + +\item{thread}{(optional) the number of parallel threads to run DAP algorithm, 1 by default. OpenMP is required for multi-thread option.} + +\item{quiet}{(optional) If TRUE, dap will mute running logs.} +} +\value{ +\code{dap} returns an object of \code{"dap"}, which is a list containing the following components: \item{signal.cluster}{a list of information on signal clusters: \describe{ +\item{cluster.summary}{a data frame, with each line representing the information of one signal cluster, including the size (i.e. number of member predictors), the posterior inclusion probability, and the average LD measures (\eqn{r^2}) for predictors within the cluster.} +\item{cluster.r2}{a matrix representing the average LD measures (\eqn{r^2}) for predictors within a cluster and between clusters.}}} +\item{variant}{a data frame of predictors ordered by the posterior inclusion probability (PIP), including predictor name, PIP, log10abf, and the signal cluster it belongs to.} +\item{model.summary}{a list of information on candidate models:\describe{ +\item{model}{a data frame of models. Specifically, the first column shows the posterior probability of the corresponding model; the second column indicates the size (i.e., the number of predictors) of the model; the third column shows the unnormalized posterior score of the model (defined as \eqn{log10(model prior)+log10(BF)}); and the last column gives the exact configuration of the model.} +\item{model.size}{information on expected model size and corresponding standard deviation.} +\item{log10NC}{log10 normalizing constant.} +\item{PIP.min}{the minimum posterior inclusion probability.} +\item{N}{the sample size.} +\item{response}{the name of the phenotype/response variable.}}} +\item{call}{the matched call.} +} +\description{ +\code{dap.z} accepts input in the format of z-scores (from single-SNP testing) and LD matrix. Note the results are typically more conservative than that from \code{dap} using individual-level data or \code{dap.ss} using sufficient statistics. +} +\examples{ +z_file = system.file("sbamsdat", "sim.1.zval.dat", package = "dap") +ld_file = system.file("sbamsdat", "sim.1.ld.dat", package = "dap") +zscores = read.table(z_file) +ld = read.table(ld_file) +dap.z(zscores, ld, n=343, pheno_name="gene") + +} diff --git a/dap_src/R-package/man/extract.sbams.Rd b/dap_src/R-package/man/extract.sbams.Rd new file mode 100644 index 0000000..d38fdb9 --- /dev/null +++ b/dap_src/R-package/man/extract.sbams.Rd @@ -0,0 +1,36 @@ +% Generated by roxygen2: do not edit by hand +% Please edit documentation in R/sbams.R +\name{extract.sbams} +\alias{extract.sbams} +\title{Extract Sufficient Statistics from a sbams file} +\usage{ +extract.sbams(file, ens = 1, pi1 = -1) +} +\arguments{ +\item{file}{file path to the sbams file} + +\item{ens}{(optional) prior expected number of signals, \code{ens=1} by default.} + +\item{pi1}{(optional) the exchangeable prior probability, values \code{0 #include diff --git a/dap_src/MLR.h b/dap_src/R-package/src/MLR.h similarity index 97% rename from dap_src/MLR.h rename to dap_src/R-package/src/MLR.h index d2c2ab1..48dddfc 100644 --- a/dap_src/MLR.h +++ b/dap_src/R-package/src/MLR.h @@ -3,6 +3,7 @@ #include #include +using namespace std; class MLR { @@ -91,6 +92,9 @@ class MLR { printf("N = %d\n",n); printf("Syy = %7.3e\n\n", yty); } + double get_syy(){ + return yty; + } // for data extraction vector beta_vec; vector se_vec; diff --git a/dap_src/R-package/src/Makevars b/dap_src/R-package/src/Makevars new file mode 100644 index 0000000..6dde2f0 --- /dev/null +++ b/dap_src/R-package/src/Makevars @@ -0,0 +1,3 @@ +# Makevars +CXX_STD = CXX11 +PKG_LIBS=-lgsl -lgslcblas \ No newline at end of file diff --git a/dap_src/R-package/src/RcppExports.cpp b/dap_src/R-package/src/RcppExports.cpp new file mode 100644 index 0000000..a6cd497 --- /dev/null +++ b/dap_src/R-package/src/RcppExports.cpp @@ -0,0 +1,54 @@ +// Generated by using Rcpp::compileAttributes() -> do not edit by hand +// Generator token: 10BE3573-1514-4C36-9D1C-5A225CD40393 + +#include + +using namespace Rcpp; + +// dap_main +List dap_main(int input_format, List arg, int quiet); +RcppExport SEXP _dap_dap_main(SEXP input_formatSEXP, SEXP argSEXP, SEXP quietSEXP) { +BEGIN_RCPP + Rcpp::RObject rcpp_result_gen; + Rcpp::RNGScope rcpp_rngScope_gen; + Rcpp::traits::input_parameter< int >::type input_format(input_formatSEXP); + Rcpp::traits::input_parameter< List >::type arg(argSEXP); + Rcpp::traits::input_parameter< int >::type quiet(quietSEXP); + rcpp_result_gen = Rcpp::wrap(dap_main(input_format, arg, quiet)); + return rcpp_result_gen; +END_RCPP +} +// read_sbams +DataFrame read_sbams(const char * data_file); +RcppExport SEXP _dap_read_sbams(SEXP data_fileSEXP) { +BEGIN_RCPP + Rcpp::RObject rcpp_result_gen; + Rcpp::RNGScope rcpp_rngScope_gen; + Rcpp::traits::input_parameter< const char * >::type data_file(data_fileSEXP); + rcpp_result_gen = Rcpp::wrap(read_sbams(data_file)); + return rcpp_result_gen; +END_RCPP +} +// extract_sbams +List extract_sbams(List arg); +RcppExport SEXP _dap_extract_sbams(SEXP argSEXP) { +BEGIN_RCPP + Rcpp::RObject rcpp_result_gen; + Rcpp::RNGScope rcpp_rngScope_gen; + Rcpp::traits::input_parameter< List >::type arg(argSEXP); + rcpp_result_gen = Rcpp::wrap(extract_sbams(arg)); + return rcpp_result_gen; +END_RCPP +} + +static const R_CallMethodDef CallEntries[] = { + {"_dap_dap_main", (DL_FUNC) &_dap_dap_main, 3}, + {"_dap_read_sbams", (DL_FUNC) &_dap_read_sbams, 1}, + {"_dap_extract_sbams", (DL_FUNC) &_dap_extract_sbams, 1}, + {NULL, NULL, 0} +}; + +RcppExport void R_init_dap(DllInfo *dll) { + R_registerRoutines(dll, NULL, CallEntries, NULL, NULL); + R_useDynamicSymbols(dll, FALSE); +} diff --git a/dap_src/controller.cc b/dap_src/R-package/src/controller.cc similarity index 80% rename from dap_src/controller.cc rename to dap_src/R-package/src/controller.cc index b64486a..65b9a99 100644 --- a/dap_src/controller.cc +++ b/dap_src/R-package/src/controller.cc @@ -1,5 +1,3 @@ -using namespace std; - #include "controller.h" #include #include @@ -12,7 +10,7 @@ using namespace std; #include #include #include -#include + void controller::initialize(char *effect_file, char *ld_file, char *grid_file, int sample_size, double syy_, int ld_format){ @@ -37,12 +35,15 @@ void controller::initialize(char *zval_file, char *ld_file, char *grid_file, int set_default_grid(); else load_grid(grid_file); + + if(sample_size <= 0) + sample_size = 1000; + N = sample_size; + pars.process_summary_data(zval_file, ld_file, sample_size, ld_format); p = pars.ld_matrix->size1; - N = sample_size; + // set an approximate smaple size to avoid errors - if(sample_size <= 0) - sample_size = 1000; set_default_options(); } @@ -68,11 +69,54 @@ void controller::initialize(char *data_file, char *grid_file){ } +void controller::initialize(vector& pheno, string phenoname, vector >& geno, vector& geno_name, char *grid_file, bool regress){ + + use_ss = 0; + + if(strlen(grid_file) == 0) + set_default_grid(); + else + load_grid(grid_file); + + pars.process_data(pheno, geno, "group", phenoname, geno_name, regress); + + p = pars.geno_vec[0].size(); + N = pars.geno_vec[0][0].size(); + + // default maximum model size + set_default_options(); + +} + +void controller::initialize(vector& snp, vector& beta, vector& se, vector>& ld, int sample_size, double syy_, string phenoname){ + use_ss = 2; + N = sample_size; + syy = syy_; + p = snp.size(); + + set_default_grid(); + + pars.process_summary_data2(snp, beta, se, ld,sample_size, syy, phenoname); + set_default_options(); +} + +void controller::initialize(vector& snp, vector& zval, vector>& ld, int sample_size, string phenoname){ + use_ss = 1; + N = sample_size; + p = snp.size(); + + set_default_grid(); + + pars.process_summary_data(snp, zval, ld, sample_size, phenoname); + set_default_options(); +} + + void controller::set_default_options(){ max_size = p; // default thread - nthread = 1; + nthread = 5; output_all = 0; size_select_thresh = 0.01; // set to big positive numbers to enforce the adaptive stopping rule @@ -84,6 +128,11 @@ void controller::set_default_options(){ log10_bf_thresh = 2; ld_control_thresh = 0.25; // by default ld control with r^2 = 0.25 + + + run_in_r = 0; + outfd = stdout; + logfd = stderr; } @@ -116,6 +165,11 @@ void controller::print_dap_config(){ fprintf(logfd,"\t* LD control threshold [-ld_control]: %.2f\n", ld_control_thresh); fprintf(logfd,"\t* normalizing constant convergence threshold [-converg_thresh]: %.2e (log10 scale)\n", size_select_thresh); + #ifdef _OPENMP + fprintf(logfd,"\t* number of parallel threads [-t]: %d\n", nthread); + #else + fprintf(logfd,"\t* number of parallel threads [-t]: 1 (OpenMP not available)\n"); + #endif } @@ -162,24 +216,28 @@ void controller::set_default_grid(){ void controller::set_outfile(char *outfile, char *logfile){ + if(run_in_r==1){ + logfd = stdout; + return; + } + if(run_in_r==2){ + fclose(stderr); + return; + } - if(strlen(outfile)==0) - outfd = stdout; - else + if(strlen(outfile)>0) outfd = fopen(outfile,"w"); - if(strlen(logfile)==0) - logfd = stderr; - else + if(strlen(logfile)>0) logfd = fopen(logfile,"w"); } // exchangeable prior pes/p -void controller::set_prior_exp(double pes){ +void controller::set_prior_default(){ - double pi1 = pes/double(p); + double pi1 = ens/double(p); set_prior(pi1); } @@ -206,8 +264,16 @@ void controller::set_prior(char *prior_file){ ifstream ifile(prior_file); string line; istringstream ins; + map::iterator it; + + // comment the following lines if prefer default as 0.0 + double pi_default = ens/(double)p; + if(pi_default > 1 - 1e-3) + pi_default = 1 - 1e-3; + pi_vec = vector(p,pi_default); - pi_vec = vector(p,0.0); + // uncomment the following line if prefer default as 0.0 +// pi_vec = vector(p,0.0); while(getline(ifile,line)){ @@ -215,11 +281,13 @@ void controller::set_prior(char *prior_file){ ins.str(line); double value; string snp_name; - ins>>snp_name; + ins>>snp_name>>value; - int index = pars.geno_rmap[snp_name]; - ins>>value; - pi_vec[index] = value; + it = pars.geno_rmap.find(snp_name); + if(it != pars.geno_rmap.end()){ + int index = it->second; + pi_vec[index] = value; + } } @@ -229,6 +297,32 @@ void controller::set_prior(char *prior_file){ } +void controller::set_prior(vector& snp_names, vector prior_values){ + int n_priors = prior_values.size(); + map::iterator it; + + // comment the following lines if prefer default as 0.0 + double pi_default = ens/(double)p; + if(pi_default > 1 - 1e-3) + pi_default = 1 - 1e-3; + pi_vec = vector(p,pi_default); + + // uncomment the following line if prefer default as 0.0 +// pi_vec = vector(p,0.0); + + for(int i=0; isecond; + pi_vec[index] = value; + } + } + +} + + void controller::init(){ if(use_ss==0){ vector > > Xgv; @@ -453,7 +547,7 @@ void controller::fine_map(){ // else check stopping point double ncps = szm.log10_sum_post; double rb = log10(double(p)-cs+1)+log10(prior_ratio) + cps; - double lb = log10(double(p-2*cs+2)/cs) + log10(prior_ratio) + cps; +// double lb = log10(double(p-2*cs+2)/cs) + log10(prior_ratio) + cps; if( ncps <= rb && val - prev_val <= size_select_thresh){ break; } @@ -464,6 +558,7 @@ void controller::fine_map(){ } summarize_approx_posterior(); + if(run_in_r==0) summary_output(); } @@ -628,7 +723,7 @@ size_model controller::append_post_model(int size, map &black_list){ map post_map; vector name_vec(ms); -#pragma omp parallel for num_threads(nthread) +#pragma omp parallel for for(int i=0;i& bm){ vector post_vec; vector abf_vec; - double max_log10_abf = -9999; +// double max_log10_abf = -9999; double max_log10_post = -9999; int max_id = -1; for(int index=0;index post_map; vector name_vec(ms); -#pragma omp parallel for num_threads(nthread) +#pragma omp parallel for for(int i=0;i wv1(log10_pmass_vec.size(),1.0); - double log10_pip_NC = mlr.log10_weighted_sum(log10_pmass_vec,wv1); +// double log10_pip_NC = mlr.log10_weighted_sum(log10_pmass_vec,wv1); double val = log10_pmass_vec[log10_pmass_vec.size()-1]; @@ -901,6 +996,11 @@ void controller::summarize_approx_posterior(){ nm.post_score = log10_pmass_vec[0]; nmodel_vec.push_back(nm); + double cump = nm.prob; + + msize_mean = 0; + msize_var = 0; + for(int i=0;i::iterator iter; @@ -910,69 +1010,37 @@ void controller::summarize_approx_posterior(){ nm.post_score = iter->second; nm.prob = pow(10, iter->second-log10_pnorm); nm.size = szm_vec[i].size; - nmodel_vec.push_back(nm); + if(nm.prob >= 1e-5) + nmodel_vec.push_back(nm); parse_nmodel(nm); - } - } - - std::sort(nmodel_vec.begin(),nmodel_vec.end(),sort_nmodel_dec); - double cump = 0; - - double msize_mean = 0; - double msize_var = 0; + cump += nm.prob; + msize_mean += nm.prob*nm.size; + msize_var += nm.prob*pow(nm.size,2); - for(int i=0;i= 1e-5 || name == "NULL"){ - fprintf(outfd, "%5d %7.4e %d %7.3f [%s]\n",i+1, nmodel_vec[i].prob, nmodel_vec[i].size, nmodel_vec[i].post_score, name.c_str()); } - cump += nmodel_vec[i].prob; - msize_mean += nmodel_vec[i].prob*nmodel_vec[i].size; - msize_var += nmodel_vec[i].prob*pow(nmodel_vec[i].size,2); - } - - msize_var -= pow(msize_mean,2.0); if(msize_var < 0){ msize_var = 0; } - - fprintf(outfd, "\nPosterior expected model size: %.3f (sd = %.3f)\n", msize_mean, sqrt(msize_var)); - fprintf(outfd, "LogNC = %.5f ( Log10NC = %.3f )", log10_pnorm/log10(exp(1)), log10_pnorm); + std::sort(nmodel_vec.begin(),nmodel_vec.end(),sort_nmodel_dec); - vector nsnp_vec_sort = nsnp_vec; - std::sort(nsnp_vec_sort.begin(),nsnp_vec_sort.end(),sort_nsnp_dec_by_ip); + std::sort(nsnp_vec.begin(),nsnp_vec.end(),sort_nsnp_dec_by_ip); map snp2index; - for(int i=0;i cluster_pip; - vector cluster_r2; - vector cluster_count; - vector cluster_id; - vector > grp_vec; - map grpr2_map; int cluster_index = 1; for(int i=0;i min_pip){ member_vec.push_back(snp); cluster_prob += prob; - nsnp_vec_sort[index].cluster = cluster_index; + nsnp_vec[index].cluster = cluster_index; } } - if(member_vec.size()>0){ - +// if(member_vec.size()>0){ +// +// cluster_r2.push_back(compute_average_r2(member_vec)); +// cluster_count.push_back(member_vec.size()); +// cluster_pip.push_back(cluster_prob); +// cluster_id.push_back(cluster_index); +// +// if(cluster_prob >= cluster_pip_thresh){ +// grp_vec.push_back(member_vec); +// grpr2_map[cluster_count.size()-1] = grp_vec.size()-1; +// } +// cluster_index++; +// } + if(member_vec.size()>0 && cluster_prob >= cluster_pip_thresh){ + cluster_r2.push_back(compute_average_r2(member_vec)); cluster_count.push_back(member_vec.size()); cluster_pip.push_back(cluster_prob); cluster_id.push_back(cluster_index); - if(cluster_prob >= cluster_pip_thresh){ - grp_vec.push_back(member_vec); - grpr2_map[cluster_count.size()-1] = grp_vec.size()-1; - } + grp_vec.push_back(member_vec); + grpr2_map[cluster_count.size()-1] = grp_vec.size()-1; cluster_index++; } } - map grp_r2; if(grp_vec.size()>1){ for(int i=0;icounti) - id = counti+":"+countk; + id = to_string(counti)+":"+to_string(countk); fprintf(outfd,"%7.3f\t",grp_r2[id]); } fprintf(outfd,"\n"); - counti++; } } - } @@ -1124,6 +1224,7 @@ double *controller::get_weights(vector& vec){ void controller::scan(){ init(); + init_scan_for_R(); mlr.get_single_SNP_stats(); for(int i=0;i0){ + single_snp_name.resize(p); + single_snp_bhat.resize(p); + single_snp_se.resize(p); + single_snp_zval.resize(p); + single_snp_log10_ABF.resize(p); + } +} +void controller::test_scan_for_R(){ + if(run_in_r>0){ + for(int i=0; i & vec){ if(vec.size()==1) return 1.0; diff --git a/dap_src/controller.h b/dap_src/R-package/src/controller.h similarity index 63% rename from dap_src/controller.h rename to dap_src/R-package/src/controller.h index f1c29e1..a81a6f0 100644 --- a/dap_src/controller.h +++ b/dap_src/R-package/src/controller.h @@ -5,6 +5,9 @@ #include #include #include +#ifdef _OPENMP +#include +#endif class NSNP { @@ -67,6 +70,7 @@ class controller { vector pi_vec; //prior for configs double prior_ratio; // for estimate residual from the approximaiton + double ens; // pes or ens - expected number of signals int max_size; //user option, maximum model size @@ -84,8 +88,7 @@ class controller { // for reporting map nsnp_map; - vector nsnp_vec; - vector nmodel_vec; + // output pip for all SNPs default only output those > 0.001 @@ -96,7 +99,7 @@ class controller { double log10_pnorm; - map single_log10_abfv; + // threshold double snp_select_thresh; // conditional inclusion prob. @@ -117,7 +120,36 @@ class controller { int nthread; int use_ss; + // run in R + int run_in_r; + public: + // for reporting option 0 + vector nmodel_vec; + vector nsnp_vec; + double msize_mean; + double msize_var; + double min_pip; + + vector cluster_pip; + vector cluster_r2; + vector cluster_count; + vector cluster_id; + vector > grp_vec; + map grpr2_map; + map grp_r2; + map single_log10_abfv; + + // for reporting option 1 --scan + vector single_snp_name; + vector single_snp_bhat; + vector single_snp_se; + vector single_snp_zval; + vector single_snp_log10_ABF; + + // for reporting ld matrix + vector ld_matrix_flat; // flat vector of size pxp + // public interface int run_option; @@ -131,6 +163,7 @@ class controller { void scan(); void extract_ss(); void extract_ss2(); + void extract_ss2_in_r(); void print_dap_config(); // system setting @@ -152,10 +185,14 @@ class controller { } - + void set_ens(double pes){ + ens = pes; + } void set_prior(char *prior_file); - void set_prior_exp(double pes); + void set_prior_default(); void set_prior(double pi1); + // for R use + void set_prior(vector& snp_names, vector prior_values); void set_max_size(int msize){ max_size = msize; @@ -185,6 +222,74 @@ class controller { void set_thread(int thread){ nthread = thread; + #ifdef _OPENMP + omp_set_num_threads(nthread); + #else + nthread=1; + #endif + } + + + // for R use + void initialize(vector& pheno, string phenoname, vector >& geno, vector& geno_name, char *grid_file, bool regress); + void initialize(vector& snp, vector& beta, vector& se, vector>& ld, int sample_size, double syy_, string phenoname); + void initialize(vector& snp, vector& zval, vector>& ld, int sample_size, string phenoname); + + void set_for_r(int quiet){ + //1:not quiet 2:quiet + run_in_r = 1 + quiet; + } + + double get_msize_mean(){ + return msize_mean; + } + + double get_msize_sd(){ + return sqrt(msize_var); + } + + double get_log10_pnorm(){ + return log10_pnorm; + } + + double get_min_pip(){ + return min_pip; + } + + int get_N(){ + return N; + } + + int get_p(){ + return p; + } + + double get_syy(){ + return syy; + } + + int get_output_all(){ + return output_all; + } + + int get_max_size(){ + return max_size; + } + + double get_ld_control_thresh(){ + return ld_control_thresh; + } + + double get_size_select_thresh(){ + return size_select_thresh; + } + + int get_nthread(){ + return nthread; + } + + string get_pheno_name(){ + return pars.pheno_name; } @@ -210,6 +315,7 @@ class controller { // reporting void summarize_approx_posterior(); + void summary_output(); // utility @@ -219,6 +325,10 @@ class controller { double compute_average_r2 (const vector & vec); double compute_average_r2(const vector & vec1, const vector & vec2); double compute_r2(int i, int j); + + // for R use + void init_scan_for_R(); + void test_scan_for_R(); }; double log10_weighted_sum(vector &vec, vector &wts); diff --git a/dap_src/R-package/src/main.cpp b/dap_src/R-package/src/main.cpp new file mode 100644 index 0000000..008b845 --- /dev/null +++ b/dap_src/R-package/src/main.cpp @@ -0,0 +1,458 @@ +#include +#include "controller.h" +#include +#include +#include + +using namespace Rcpp; +using namespace std; + +List summary_option_0(controller& con); +List summary_option_1(controller& con); +void print_dap_config(controller& con); + +// [[Rcpp::export]] +List dap_main(int input_format, List arg, int quiet) { + // input_format + // 1: data_file (string) + // 2: data x,y (NumericMatrix, NumericVector) + // 3: summary statistics (Vectors) + // 4: zval (Vectors) + + char grid_file[128]; + char data_file[128]; + char out_file[128]; + char log_file[128]; + char gene_name[64]; + + + memset(gene_name,0,64); + memset(grid_file,0,128); + memset(out_file,0,128); + memset(log_file,0,128); + memset(data_file,0,128); + + // int ld_format = 1; // for correlation matrix + // for now the R-package allows ld in format 1 only!!! + + double abf_option = -1; + + int msize =-1; + + int output_all = 0; + + bool has_prior_data = false; + double pes = 1.0; + double pi1 = -1; + // double lambda = 0.5; + double ld_control = -1; + + int size_limit = -1; + + int sample_size = -1; + double syy = -1; + + double snp_select_thresh = -1; + double size_select_thresh = -1; + + // alternative non-fm running options + int run_scan = 0; + int extract_ss = 0; + + int thread = 1; + + + vector< string > mystrings = arg.attr("names"); + + for(int i=0; i genonames = as>(colnames(x)); + vector pheno = as>(y); + vector> geno; + geno.resize(n_gene); + for(int i=0; i>(v); + geno[i].resize(n_ind); + } + con.initialize(pheno, name, geno, genonames, grid_file, true); + }else if(input_format==3){ + + StringVector snp_name = arg["snp_names"]; + NumericVector est = arg["beta"]; + NumericVector est_se = arg["se"]; + NumericMatrix ld_matrix = arg["ld"]; + string name = arg["pheno_name"]; + + int p = snp_name.size(); + vector genonames = as>(snp_name); + vector beta = as>(est); + vector se = as>(est_se); + vector> ld; + ld.resize(p); + for(int i=0; i>(v); + ld[i].resize(p); + } + + con.initialize(genonames, beta, se, ld, sample_size, syy, name); + }else if(input_format==4){ + + StringVector snp_name = arg["snp_names"]; + NumericVector est = arg["zvals"]; + NumericMatrix ld_matrix = arg["ld"]; + string name = arg["pheno_name"]; + + int p = snp_name.size(); + vector genonames = as>(snp_name); + vector zvals = as>(est); + vector> ld; + ld.resize(p); + for(int i=0; i>(v); + ld[i].resize(p); + } + + con.initialize(genonames, zvals, ld, sample_size, name); + } + + con.set_for_r(quiet); + + con.set_outfile(out_file, log_file); + + con.set_gene(gene_name); + con.set_abf_option(abf_option); + con.set_thread(thread); + + con.set_size_limit(size_limit); + + if(ld_control>=0) + con.set_ld_control(ld_control); + + if(msize>=1){ + con.set_max_size(msize); + } + + + if(pes>0){ + con.set_ens(pes); + } + + + if(!has_prior_data){ + if(pi1 != -1){ + if(0 prior_snp_names = as>(prior_snp_names_r); + vector prior_values = as>(prior_values_r); + con.set_prior(prior_snp_names, prior_values); + } + + + + if(output_all == 1) + con.set_output_all(); + + if(snp_select_thresh>=0) + con.set_snp_select_thresh(snp_select_thresh); + + if(size_select_thresh >=0) + con.set_size_select_thresh(size_select_thresh); + + con.run_option = 0; + + if(run_scan){ + con.run_option = 1; + } + + if(extract_ss==1){ + con.run_option =2; + } + if(extract_ss==2){ + con.run_option =3; + } + + + // all done, print all configs + if(quiet==0) print_dap_config(con); + + con.run(); + + if(con.run_option==0) return summary_option_0(con); + if(con.run_option==1) return summary_option_1(con); + + // API not built for other options + return List::create(); + +} + + +List summary_option_0(controller& con){ + int n_nmodel = con.nmodel_vec.size(); + NumericVector nmodel_prob, nmodel_post; + IntegerVector nmodel_size; + CharacterVector nmodel_name; + + for(int i=0;i 0){ + DataFrame cluster = DataFrame::create(Named("cluster.size") = wrap(con.cluster_count), + Named("cluster.pip") = wrap(con.cluster_pip), + Named("average.r2") = wrap(con.cluster_r2)); + + int n_cluster = con.cluster_count.size(); + NumericMatrix r2 (n_cluster); + for(int i=0; icounti) + id = to_string(counti)+":"+to_string(countk); + r2(i,k) = con.grp_r2[id]; + r2(k,i) = r2(i,k); + } + } + rownames(r2) = wrap(con.cluster_id); + colnames(r2) = rownames(r2); + + List signal_cluster = List::create(Named("cluster.summary") = cluster, + Named("cluster.r2") = r2); + + result.push_front(signal_cluster, "signal.cluster"); + } + + return result; +} + +List summary_option_1(controller& con){ + DataFrame result = DataFrame::create(Named("SNP")=con.single_snp_name, + Named("log10_ABF")=con.single_snp_log10_ABF, + Named("b")=con.single_snp_bhat, + Named("se")=con.single_snp_se, + Named("z-value")=con.single_snp_zval); + return List::create(result); +} + +void print_dap_config(controller& con){ + Rcout << "\n============ DAP Configuration ============\n\n"; + Rcout << "INPUT\n\n"; + + Rcout << "\t* individual-level data\n"; + Rprintf("\t* number of candidate predictors: %i\n", con.get_p()); + Rprintf("\t* sample size: %i\n\n", con.get_N()); + + Rcout << "PROGRAM OPTIONS\n\n"; + Rprintf("\t* maximum model size allowed [ msize = %i ] ", con.get_max_size()); + if(con.get_max_size()==con.get_p()) + Rcout << "(no restriction)\n"; + else + Rcout << "\n"; + + Rprintf("\t* LD control threshold [ ld_control = %.2f ]\n", con.get_ld_control_thresh()); + Rprintf("\t* normalizing constant convergence threshold [ converg_thresh = %.2e ] (log10 scale)\n", con.get_size_select_thresh()); + + #ifdef _OPENMP + Rprintf("\t* number of parallel threads [ thread = %i ]\n", con.get_nthread()); + #else + Rcout << "\t* number of parallel threads [ thread = 1 ] (OpenMP not available)\n"; + #endif + + Rcout << "\n===========================================\n"; +} + + diff --git a/dap_src/parser.cc b/dap_src/R-package/src/parser.cc similarity index 82% rename from dap_src/parser.cc rename to dap_src/R-package/src/parser.cc index 7434879..276a223 100644 --- a/dap_src/parser.cc +++ b/dap_src/R-package/src/parser.cc @@ -1,5 +1,3 @@ -using namespace std; - #include "parser.h" #include "stdlib.h" #include @@ -104,6 +102,36 @@ void parser::process_summary_data2(char *effect_file, char *ld_file, int sample_ } +void parser::process_summary_data2(vector& snp_names, vector& beta_vector, vector& se_vector, vector>& ld, int sample_size, double syy, string name){ + pheno_name = name; + int p = snp_names.size(); + ld_matrix = gsl_matrix_calloc(p,p); + + for(int i=0; i& snp_names, vector& z_vector, vector>& ld, int sample_size, string name){ + pheno_name = name; + int p = snp_names.size(); + + zval_matrix = gsl_matrix_calloc(p,1); + ld_matrix = gsl_matrix_calloc(p,p); + + for(int i=0; i0){ + double h2 = zval*zval/(zval*zval+sample_size); + double factor = sqrt(0.5*(1+1/(1-h2))); + zval = zval/factor; + } + gsl_matrix_set(zval_matrix,i,0,zval); + + for(int j=i; j& pheno, vector >& geno, string grp, string name, vector& geno_name, bool regress){ + // Notice: do not support multi-group! + // Does not support controlled variates for now. + + covar_vec.resize(1); + + pheno_vec.resize(1); + pheno_name = name; + pheno_vec[0] = pheno; + pheno_map[0] = grp; + pheno_index[string(grp)] = 0; + + geno_vec.resize(1); + geno_vec[0] = geno; + for(int i=0; i #include +using namespace std; + class parser { @@ -18,7 +20,7 @@ class parser { vector > pheno_vec; map pheno_map; - map pheno_index;; + map pheno_index; map geno_map; map geno_rmap; @@ -34,8 +36,11 @@ class parser { void process_summary_data(char *zval_file, char *ld_file, int sample_size = -1, int ld_format=1); void process_summary_data2(char *effect_file, char *ld_file, int sample_size, double syy,int ld_format=1); void output(); - - + + // for R use only + void process_data(vector& pheno, vector >& geno, string grp, string name, vector& geno_name, bool regress); + void process_summary_data2(vector& snp_names, vector& beta_vector, vector& se_vector, vector>& ld, int sample_size, double syy, string name); + void process_summary_data(vector& snp_names, vector& z_vector, vector>& ld, int sample_size, string name); diff --git a/dap_src/R-package/src/sbams.cpp b/dap_src/R-package/src/sbams.cpp new file mode 100644 index 0000000..51f6236 --- /dev/null +++ b/dap_src/R-package/src/sbams.cpp @@ -0,0 +1,166 @@ +#include +#include "controller.h" +#include +#include +#include +#include +#include +#include +#include + +using namespace Rcpp; +using namespace std; + +// [[Rcpp::export]] +DataFrame read_sbams(const char * data_file){ + char filename[128]; + memset(filename,0,128); + strcpy(filename, data_file); + + parser pars; + pars.process_data(filename); + + if(pars.pheno_vec.size()==0) + stop("[Error] No phenotype information found in the file!\n"); + if(pars.geno_vec.size()==0) + stop("[Error] No genotype information found in the file!\n"); + + if(pars.pheno_vec.size()!=1 || pars.geno_vec.size()!=1) + stop("Please contact the author for support of multi-group sbams files.\n"); + + List result_list = wrap(pars.geno_vec[0]); + result_list.names() = wrap(pars.geno_map); + result_list.push_front(wrap(pars.pheno_vec[0]), pars.pheno_name); + + DataFrame result = result_list; + return result; +} + + +// [[Rcpp::export]] +List extract_sbams(List arg){ + char grid_file[128]; + char data_file[128]; + char out_file[128]; + char log_file[128]; + char gene_name[64]; + + + memset(gene_name,0,64); + memset(grid_file,0,128); + memset(out_file,0,128); + memset(log_file,0,128); + memset(data_file,0,128); + + double abf_option = -1; + + bool has_prior_data = false; + double pes = 1.0; + double pi1 = -1; + + + vector< string > mystrings = arg.attr("names"); + + for(int i=0; i0){ + con.set_ens(pes); + } + + + if(!has_prior_data){ + if(pi1 != -1){ + if(0 prior_snp_names = as>(arg["prior_snp_names"]); + vector prior_values = as>(arg["prior_values"]); + con.set_prior(prior_snp_names, prior_values); + } + + con.extract_ss2_in_r(); + + int p = con.get_p(); + NumericVector ld_matrix_flat = wrap(con.ld_matrix_flat); + ld_matrix_flat.attr("dim") = Dimension(p,p); + NumericMatrix ld_matrix = as(ld_matrix_flat); + + DataFrame est = DataFrame::create(Named("snp")=wrap(con.single_snp_name), + Named("b") =wrap(con.single_snp_bhat), + Named("se") =wrap(con.single_snp_se)); + + return List::create(Named("est")=est, + Named("ld") =ld_matrix, + Named("n") =con.get_N(), + Named("syy")=con.get_syy(), + Named("name")=con.get_pheno_name()); +} + + + diff --git a/dap_src/README.md b/dap_src/README.md index f09445b..4e40049 100644 --- a/dap_src/README.md +++ b/dap_src/README.md @@ -2,14 +2,14 @@ ## 1. Compilation -The following C/C++ libraries are required for compiling the source code +The following C/C++ library is required for compiling the source code * GNU [GSL](http://www.gnu.org/software/gsl/) library -* [OpenMP](http://openmp.org/wp/openmp-compilers/) compiler (many popular compilers are compatible) -Simply run ``make`` to compile the executable named ``dap``. +The following C/C++ library is optional but recommended +* [OpenMP](http://openmp.org/wp/openmp-compilers/) compiler (many popular compilers are compatible) -Run ``make static`` to compile an executable with static linked library. +Simply run ``bash install.sh`` to compile the executable named ``dap-g`` in folder ``bin``. ## 2. Command-line Syntax diff --git a/dap_src/install.sh b/dap_src/install.sh new file mode 100644 index 0000000..db4847f --- /dev/null +++ b/dap_src/install.sh @@ -0,0 +1,10 @@ +#!/bin/sh + +rm -rf bin/ +mkdir bin +cd bin/ +echo -e "Generating MakeFiles ..." +cmake .. +make +echo "Binary created at /bin/dap-g" + diff --git a/dap_src/src/MLR.cc b/dap_src/src/MLR.cc new file mode 100644 index 0000000..4c725fc --- /dev/null +++ b/dap_src/src/MLR.cc @@ -0,0 +1,742 @@ +#include "MLR.h" +#include +#include +#include +#include +#include + +void MLR::init(double yty_, const gsl_matrix *GtG_, const gsl_matrix *Gty_, int n_){ + + n = n_; + p = GtG_->size1; + yty = yty_; + + GtG = gsl_matrix_calloc(p,p); + Gty = gsl_matrix_calloc(p,1); + gsl_matrix_memcpy(GtG, GtG_); + gsl_matrix_memcpy(Gty, Gty_); + use_ss = 0; +} + +void MLR::init_ss(const gsl_matrix *Z_, const gsl_matrix *R_){ + + p = R_->size1; + use_ss = 1; + + R = gsl_matrix_calloc(p,p); + Z = gsl_matrix_calloc(p,1); + gsl_matrix_memcpy(R, R_); + gsl_matrix_memcpy(Z, Z_); + +} + + + + +void MLR::init(vector &Y_in, vector > &G_in){ + + n = Y_in.size(); + p = G_in.size(); + + yty = 0; + Y = gsl_matrix_calloc(n,1); + for(int i=0;i &indicator){ + if(mlr.use_ss == 0) + copy_full(mlr, indicator); + else + copy_ss(mlr, indicator); +} + + + + +void MLR::copy_ss(const MLR & mlr){ + + if(mlr.use_ss ==0) + return; + use_ss = 1; + n = mlr.n; + p = mlr.p; + + if(mlr.R != 0){ + R = gsl_matrix_calloc(p,p); + gsl_matrix_memcpy(R, mlr.R); + } + if(mlr.Z != 0){ + Z = gsl_matrix_calloc(p,1); + gsl_matrix_memcpy(Z,mlr.Z); + } + sigma_option = mlr.sigma_option; + phi2_vec = mlr.phi2_vec; + + +} + + +void MLR::copy_ss(const MLR & mlr, vector & indicator){ + if(mlr.use_ss == 0) + return; + use_ss = 1; + n = mlr.n; + + int tp = mlr.p; + int ep = 0; + int count = 0; + std::map imap; + + + for(int i=0;i & indicator){ + + if(mlr.use_ss == 1) + return; + + use_ss = 0; + n = mlr.n; + yty = mlr.yty; + + int tp = mlr.p; + int ep = 0; + int count = 0; + std::map imap; + + + for(int i=0;i &phi2_vec_){ + + phi2_vec = phi2_vec_; + +} + + +double MLR::compute_log10_ABF(){ + vector indicator(p,1); + return(compute_log10_ABF(indicator)); +} + + + +double MLR::compute_log10_ABF(vector & indicator){ + + if(!use_ss){ + if(sigma_option>=0 && sigma_option <=1) + return compute_log10_ABF_FD(indicator); + else + return compute_log10_BF_FD(indicator); + }else + return compute_log10_ABF_SS(indicator); + + +} + + + + + +double MLR::compute_log10_BF_FD(vector & indicator){ + + vector rstv; + vector wv; + + + int ep = 0; + int count = 0; + std::map imap; + + + for(int i=0;i1e-8){ + gsl_matrix_set(tt1,j,j,1.0/v); + } + } + + + + gsl_matrix *tt2 = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,V,tt1,0,tt2); + + gsl_matrix *IWV = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasTrans,1,tt2,V,0,IWV); + + + gsl_matrix *tt3 = gsl_matrix_calloc(ep,1); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,IWV,Xty,0,tt3); + + gsl_matrix *tt4 = gsl_matrix_calloc(1,1); + gsl_blas_dgemm(CblasTrans,CblasNoTrans,1,Xty,tt3,0,tt4); + + double b_rss = gsl_matrix_get(tt4,0,0); + double log10BF = -0.5*log10(fabs(det)) - 0.5*n*log10(1 - b_rss/yty); + + rstv.push_back(log10BF); + wv.push_back(1.0/phi2_vec.size()); + + + gsl_matrix_free(tt1); + gsl_matrix_free(tt2); + gsl_matrix_free(IWV); + gsl_matrix_free(tt3); + gsl_matrix_free(tt4); + + + } + + gsl_matrix_free(V); + gsl_vector_free(S); + gsl_vector_free(work); + + gsl_matrix_free(XtX); + gsl_matrix_free(Xty); + + + double rst = log10_weighted_sum(rstv,wv); + + return rst; + +} + + +// ABF with full data +double MLR::compute_log10_ABF_FD(vector & indicator){ + + + // construct the sub-matrices + + vector rstv; + vector wv; + + + int ep = 0; + int count = 0; + std::map imap; + + + for(int i=0;i1e-8){ + gsl_matrix_set(t1,i,i,1/v); + } + } + gsl_matrix *t2 = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,V,t1,0,t2); + + + + gsl_matrix *XtX_inv = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasTrans,1,t2,V,0,XtX_inv); + + + + + // compute sigma + gsl_matrix *t3 = gsl_matrix_calloc(ep,1); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,XtX_inv,Xty,0,t3); + + gsl_matrix *t4 = gsl_matrix_calloc(1,1); + gsl_blas_dgemm(CblasTrans,CblasNoTrans,1,Xty,t3,0,t4); + + double res = yty - gsl_matrix_get(t4,0,0); + + double sigma2 = (sigma_option*res + (1-sigma_option)*yty)/n; + + + // compute BF + for(int i=0;i1e-8){ + gsl_matrix_set(tt1,j,j,1.0/v); + } + } + + + gsl_matrix *tt2 = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,V,tt1,0,tt2); + + gsl_matrix *IWV = gsl_matrix_calloc(ep,ep); + gsl_blas_dgemm(CblasNoTrans,CblasTrans,1,tt2,V,0,IWV); + + gsl_matrix *tt3 = gsl_matrix_calloc(ep,1); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,IWV,Xty,0,tt3); + + gsl_matrix *tt4 = gsl_matrix_calloc(1,1); + gsl_blas_dgemm(CblasTrans,CblasNoTrans,1,Xty,tt3,0,tt4); + + double log10BF = (-0.5*log(fabs(det))+0.5*gsl_matrix_get(tt4,0,0)/sigma2)/log(10); + + rstv.push_back(log10BF); + wv.push_back(1.0/phi2_vec.size()); + + + gsl_matrix_free(tt1); + gsl_matrix_free(tt2); + gsl_matrix_free(IWV); + gsl_matrix_free(tt3); + gsl_matrix_free(tt4); + + + } + + + + gsl_matrix_free(V); + gsl_vector_free(S); + gsl_vector_free(work); + gsl_matrix_free(t1); + gsl_matrix_free(t2); + gsl_matrix_free(XtX_inv); + + gsl_matrix_free(t3); + gsl_matrix_free(t4); + + gsl_matrix_free(XtX); + gsl_matrix_free(Xty); + + + double rst = log10_weighted_sum(rstv,wv); + + return rst; +} + +double MLR::compute_log10_ABF_SS(vector & indicator){ + + // construct the sub-matrices + + vector rstv; + + int ep = 0; + int count = 0; + std::map imap; + + + for(int i=0;i wv(phi2_vec.size(), 1.0/phi2_vec.size()); + double rst = log10_weighted_sum(rstv,wv); + return rst; + + + + +} + + + + +// utility + +double MLR::log10_weighted_sum(vector &vec, vector &wts){ + + + double max = vec[0]; + for(size_t i=0;imax) + max = vec[i]; + } + double sum = 0; + for(size_t i=0;i +#include +#include +#include + +using namespace std; + +class MLR { + + private: + + + int p; // genotype size + int n; // sample size + + // full summary data input + gsl_matrix *GtG; + gsl_matrix *Gty; + double yty; + + // full data input + gsl_matrix *Y; + gsl_matrix *G; + + + // partial summary data input + gsl_matrix *Z; + gsl_matrix *R; + + + + vector phi2_vec; //effect size grid full data + vector kv_vec; //effect size grid summary-level data + + int use_ss; + + private: + // options + double sigma_option; // 0 to 1, mixture fraction of mle of Sigma under the alternative model, default 0 + + + + public: + + // interface + // empty constructor, assign default options + MLR(){ + sigma_option = -1; + GtG= Gty = 0; + G = Y = 0; + Z = R = 0; + use_ss = 0; + } + + ~MLR(); + + // Note: assuming covariates are regressed beforehand, typically in parser. + // init + void init(double yty_, const gsl_matrix *GtG_, const gsl_matrix *Gty_, int n_); + void init(vector &Y_in, vector > &G_in); + void init_ss(const gsl_matrix *Z_, const gsl_matrix *R_); + void copy(const MLR &mlr); + void copy(const MLR &mlr, vector & indicator); + void copy_full(const MLR &mlr); + void copy_full(const MLR &mlr, vector & indicator); + void copy_ss(const MLR &mlr); + void copy_ss(const MLR &mlr, vector & indicator); + // options + void set_effect_vec(vector &phi2); + void set_abf_option(double option){ + sigma_option = option; + } + + + double log10_weighted_sum(vector &vec, vector &wts); + + double compute_log10_ABF(); + double compute_log10_ABF(vector &indicator); + double compute_log10_ABF_FD(vector &indicator); + double compute_log10_BF_FD(vector &indicator); + double compute_log10_ABF_SS(vector &indicator); + + void extract_summary(); + gsl_matrix * get_R(){ + return R; + } + gsl_matrix * get_Z(){ + return Z; + } + + void get_summary(){ + printf("N = %d\n",n); + printf("Syy = %7.3e\n\n", yty); + } + double get_syy(){ + return yty; + } + // for data extraction + vector beta_vec; + vector se_vec; + void print_matrix(gsl_matrix *M, int a, int b, FILE *outfd = 0); + void get_single_SNP_stats(); +}; + + diff --git a/dap_src/src/controller.cc b/dap_src/src/controller.cc new file mode 100644 index 0000000..65b9a99 --- /dev/null +++ b/dap_src/src/controller.cc @@ -0,0 +1,1443 @@ +#include "controller.h" +#include +#include +#include +#include +#include +#include +#include +#include +#include +#include +#include + + +void controller::initialize(char *effect_file, char *ld_file, char *grid_file, int sample_size, double syy_, int ld_format){ + + use_ss = 2; + N = sample_size; + syy = syy_; + + if(strlen(grid_file) == 0) + set_default_grid(); + else + load_grid(grid_file); + + pars.process_summary_data2(effect_file, ld_file,sample_size, syy, ld_format); + p = pars.ld_matrix->size1; + set_default_options(); +} + +void controller::initialize(char *zval_file, char *ld_file, char *grid_file, int sample_size, int ld_format){ + + use_ss = 1; + if(strlen(grid_file) == 0) + set_default_grid(); + else + load_grid(grid_file); + + if(sample_size <= 0) + sample_size = 1000; + N = sample_size; + + pars.process_summary_data(zval_file, ld_file, sample_size, ld_format); + p = pars.ld_matrix->size1; + + // set an approximate smaple size to avoid errors + + set_default_options(); +} + + +void controller::initialize(char *data_file, char *grid_file){ + + use_ss = 0; + + if(strlen(grid_file) == 0) + set_default_grid(); + else + load_grid(grid_file); + + pars.process_data(data_file); + + p = pars.geno_vec[0].size(); + N = pars.geno_vec[0][0].size(); + + // default maximum model size + set_default_options(); + +} + + +void controller::initialize(vector& pheno, string phenoname, vector >& geno, vector& geno_name, char *grid_file, bool regress){ + + use_ss = 0; + + if(strlen(grid_file) == 0) + set_default_grid(); + else + load_grid(grid_file); + + pars.process_data(pheno, geno, "group", phenoname, geno_name, regress); + + p = pars.geno_vec[0].size(); + N = pars.geno_vec[0][0].size(); + + // default maximum model size + set_default_options(); + +} + +void controller::initialize(vector& snp, vector& beta, vector& se, vector>& ld, int sample_size, double syy_, string phenoname){ + use_ss = 2; + N = sample_size; + syy = syy_; + p = snp.size(); + + set_default_grid(); + + pars.process_summary_data2(snp, beta, se, ld,sample_size, syy, phenoname); + set_default_options(); +} + +void controller::initialize(vector& snp, vector& zval, vector>& ld, int sample_size, string phenoname){ + use_ss = 1; + N = sample_size; + p = snp.size(); + + set_default_grid(); + + pars.process_summary_data(snp, zval, ld, sample_size, phenoname); + set_default_options(); +} + + +void controller::set_default_options(){ + + max_size = p; + // default thread + nthread = 5; + + output_all = 0; + size_select_thresh = 0.01; // set to big positive numbers to enforce the adaptive stopping rule + snp_select_thresh = 0.01; + + + cluster_pip_thresh = 0.25; // for output cluster purpose + priority_msize = 100; + log10_bf_thresh = 2; + + ld_control_thresh = 0.25; // by default ld control with r^2 = 0.25 + + + run_in_r = 0; + outfd = stdout; + logfd = stderr; +} + + +// =============== summarize all configuations ====================== + + +void controller::print_dap_config(){ + fprintf(logfd,"\n============ DAP Configuration ============\n\n"); + fprintf(logfd,"INPUT\n\n"); + if(use_ss){ + fprintf(logfd,"\t* summary-level data (z-scores and LD matrix)\n"); + fprintf(logfd,"\t* number of candidate SNPs: %d\n",p); + }else{ + fprintf(logfd,"\t* individual-level data (sbams format)\n"); + fprintf(logfd,"\t* number of candidate SNPs: %d\n",p); + fprintf(logfd,"\t* sample size: %d\n",int(pars.geno_vec[0][0].size())); + fprintf(logfd,"\t* number of covariates: %d\n", int(pars.covar_vec[0].size())); + } + fprintf(logfd,"\n"); + + fprintf(logfd, "PROGRAM OPTIONS\n\n"); + + if(run_option==0){ + fprintf(logfd,"\t* maximum model size allowed [-msize]: %d ",max_size); + if(max_size ==p){ + fprintf(logfd,"(no restriction)\n"); + }else{ + fprintf(logfd,"\n"); + } + + fprintf(logfd,"\t* LD control threshold [-ld_control]: %.2f\n", ld_control_thresh); + fprintf(logfd,"\t* normalizing constant convergence threshold [-converg_thresh]: %.2e (log10 scale)\n", size_select_thresh); + #ifdef _OPENMP + fprintf(logfd,"\t* number of parallel threads [-t]: %d\n", nthread); + #else + fprintf(logfd,"\t* number of parallel threads [-t]: 1 (OpenMP not available)\n"); + #endif + } + + + if(run_option==0) + fprintf(logfd,"\nRUN LOG\n"); +} + + + +void controller::load_grid(char *grid_file){ + ifstream gfile(grid_file); + string line; + istringstream ins; + + while(getline(gfile,line)){ + + ins.clear(); + ins.str(line); + double omg; + if(ins>>omg){ + if(use_ss!=1) + omg2_vec.push_back(pow(omg,2)); + else + kv_vec.push_back(omg); + } + } + gfile.close(); + +} + +void controller::set_default_grid(){ + if(use_ss!=1){ + omg2_vec.push_back(0.04); + omg2_vec.push_back(0.16); + omg2_vec.push_back(0.64); + }else{ + kv_vec.push_back(4); + kv_vec.push_back(16); + kv_vec.push_back(25); + } + + +} + + +void controller::set_outfile(char *outfile, char *logfile){ + if(run_in_r==1){ + logfd = stdout; + return; + } + if(run_in_r==2){ + fclose(stderr); + return; + } + + if(strlen(outfile)>0) + outfd = fopen(outfile,"w"); + + + if(strlen(logfile)>0) + logfd = fopen(logfile,"w"); +} + + +// exchangeable prior pes/p +void controller::set_prior_default(){ + + double pi1 = ens/double(p); + set_prior(pi1); +} + + + +// exchangeable prior pi1 +void controller::set_prior(double pi1){ + + if(pi1 > 1 - 1e-3) + pi1 = 1-1e-3; + + for(int i=0;i::iterator it; + + // comment the following lines if prefer default as 0.0 + double pi_default = ens/(double)p; + if(pi_default > 1 - 1e-3) + pi_default = 1 - 1e-3; + pi_vec = vector(p,pi_default); + + // uncomment the following line if prefer default as 0.0 +// pi_vec = vector(p,0.0); + + while(getline(ifile,line)){ + + ins.clear(); + ins.str(line); + double value; + string snp_name; + ins>>snp_name>>value; + + it = pars.geno_rmap.find(snp_name); + if(it != pars.geno_rmap.end()){ + int index = it->second; + pi_vec[index] = value; + } + + } + + return; + + +} + + +void controller::set_prior(vector& snp_names, vector prior_values){ + int n_priors = prior_values.size(); + map::iterator it; + + // comment the following lines if prefer default as 0.0 + double pi_default = ens/(double)p; + if(pi_default > 1 - 1e-3) + pi_default = 1 - 1e-3; + pi_vec = vector(p,pi_default); + + // uncomment the following line if prefer default as 0.0 +// pi_vec = vector(p,0.0); + + for(int i=0; isecond; + pi_vec[index] = value; + } + } + +} + + +void controller::init(){ + if(use_ss==0){ + vector > > Xgv; + + Xgv = pars.geno_vec; + + if(Xgv.size() == 0) + exit(0); + // set SSLR parameters and options + mlr.set_abf_option(abf_sigma_option); + mlr.init(pars.pheno_vec[0],Xgv[0]); + + //sslr.set_prior_option(sslr_prior_option); + mlr.set_effect_vec(omg2_vec); + + }else if(use_ss==1){ + mlr.init_ss(pars.zval_matrix, pars.ld_matrix); + mlr.set_effect_vec(kv_vec); + }else if(use_ss==2){ + gsl_matrix *GtG = gsl_matrix_calloc(p,p); + gsl_matrix_memcpy(GtG,pars.ld_matrix); + gsl_matrix *Gty = gsl_matrix_calloc(p,1); + + for(int i=0;i(p,0); + //start with empty table + + double sum = 0; + for(int i=0;i &mcfg){ + + double lp=0; + for(int i=0;i log10_pmass_vec; + + + + double curr_val = compute_log10_prior(null_config); + log10_pmass_vec.push_back(curr_val); + + + fprintf(logfd, "\n\n\tModel_Size \tcandidates \t log10(NC)\n"); + + // record best model + vector bm; + // single SNP scan, label candidate SNPs for higher order models + szm_vec.push_back(compute_post_model_single(bm)); + log10_pmass_vec.push_back(szm_vec[0].log10_sum_post); + vector wv(log10_pmass_vec.size(),1.0); + double val = log10_weighted_sum(log10_pmass_vec,wv); + int total_snp = szm_vec[0].mvec.size(); + fprintf(logfd, "\t %4d \t \t %4d \t \t %9.3f\n",1,total_snp,val); + + double prev_val = val; + int size = 1; + int no_bc = 0; + double increment; + + while(1){ + + // if already at allowed max size, quit search + if(bm.size() == max_size) + break; + + // attempt to add one more variable + double log10_post = conditional_est(bm); + + // if no more variable to add, then quit search + if(size == bm.size()) + break; + else + size++; + + + // perform backwards checking, see if can eliminate one variable + int elim_index = -1; + if(size >= 3 && !no_bc){ + elim_index = backward_checking(bm, log10_post); + if(elim_index !=-1){ + size--; + } + } + + + fprintf(logfd,"\t %4d \t \t ",size); + fflush(logfd); + + size_model szm; + + double cps = szm_vec[szm_vec.size()-1].log10_sum_post; + // append an equal size model to correct for necessary backward checking + if(elim_index != -1){ + + map black_list; + for(int i=0;i nwv(log10_pmass_vec.size(),1.0); + val = log10_weighted_sum(log10_pmass_vec,nwv); + total_snp += cand_set.size(); + fprintf(logfd, "%4d \t \t %9.3f\t*\n",total_snp,val); + // stop continuous backward checking for tiny improvement + if(val - prev_val < size_select_thresh) + no_bc = 1; + + }else{ + //allow backward checking if adding a new variable + if(no_bc) + no_bc = 0; + + // append a size + int use_abs_cutoff = 0; + if(increment > 1 || size == 2) + use_abs_cutoff = 1; + + + szm = compute_post_model(size, use_abs_cutoff); + szm.snp_cluster = cand_set; + szm_vec.push_back(szm); + for(int i=0;i nwv(log10_pmass_vec.size(),1.0); + val = log10_weighted_sum(log10_pmass_vec,nwv); + total_snp += cand_set.size(); + fprintf(logfd, "%4d \t \t %9.3f\n",total_snp,val); + } + + + + // stopping rule + + int cs = size; + // if the prior expectation is high for number of signals, carry on + + // expected contribution of next size partition, assuming model is saturated + double project_ratio = (p-cs+1)*prior_ratio/cs; + if(project_ratio > 1){ + increment = val - prev_val; + prev_val = val; + continue; + } + // else check stopping point + double ncps = szm.log10_sum_post; + double rb = log10(double(p)-cs+1)+log10(prior_ratio) + cps; +// double lb = log10(double(p-2*cs+2)/cs) + log10(prior_ratio) + cps; + if( ncps <= rb && val - prev_val <= size_select_thresh){ + break; + } + + increment = val - prev_val; + prev_val = val; + //fprintf(stderr, "increment = %.3f\n", increment); + + } + summarize_approx_posterior(); + if(run_in_r==0) summary_output(); + +} + + + + +double controller::conditional_est(vector& bm){ + + cand_set.clear(); + + double max = -9999; + + vector mcfg = null_config; + + + for(int i=0;i post_vec; + + int max_id; + for(int i=0;i cmcfg = mcfg; + + + cmcfg[i] = 1; + + + double rst = mlr.compute_log10_ABF(cmcfg) + compute_log10_prior(cmcfg); + post_vec.push_back(rst); + + if(rst > max){ + max= rst; + max_id = i; + } + + } + + double thresh = -99999; + + + if(post_vec.size()>size_limit){ + vector post_vec_sort = post_vec; + sort(post_vec_sort.rbegin(), post_vec_sort.rend()); + thresh = post_vec_sort[size_limit-1]; + } + + int flag = 0; + if(max > -9999){ + for(int i=0;i=thresh){ + if(compute_r2(max_id,i)< ld_control_thresh) + continue; + cand_set.push_back(i); + cand_map[i]=1; + flag =1; + } + + } + } + + if(flag == 1) + bm.push_back(max_id); + + return max; +} + + +// backwards elimination checking +int controller::backward_checking(vector& bm, double log10_post){ + + + double max = -99999; + int max_snp = -1; + int max_id = -1; + + + for(int i=0; i tm = bm; + tm.erase(tm.begin()+i); + + vector mcfg = null_config; + + for(int j=0;j max){ + max= rst; + max_snp = bm[i]; + max_id=i; + } + + } + + if(max-log10_post>0){ + bm.erase(bm.begin()+max_id); + return snp2cluster_map[max_snp]; + } + + + return -1; + +} + +size_model controller::append_post_model(int size, map &black_list){ + + size_model smod; + smod.size = size; + smod.log10_sum_post = 0; + + vector > & model_vec = szm_vec[szm_vec.size()-1].mvec; + vector > mc_vec; + + map saved_model_string_map; + + for(int i=0; i cm = model_vec[i]; + + for(int k=0;k post_vec(mc_vec.size()); + int ms = mc_vec.size(); + + map post_map; + vector name_vec(ms); + +#pragma omp parallel for + for(int i=0;i mcfg = null_config; + vector cm = mc_vec[i]; + + string name =""; + for(int j=0;j rst_post_vec; + map rst_post_map; + vector > rst_mc_vec; + + vector post_vec_sort = post_vec; + sort(post_vec_sort.rbegin(), post_vec_sort.rend()); + + double cutoff = post_vec_sort[0] - 2; + + for(int i=0;i= cutoff){ + rst_post_vec.push_back(post_vec[i]); + rst_mc_vec.push_back(mc_vec[i]); + rst_post_map[name_vec[i]] = post_vec[i]; + } + } + + vector wv(rst_post_vec.size(),1.0); + smod.log10_sum_post = mlr.log10_weighted_sum(rst_post_vec,wv); + smod.post_map = rst_post_map; + smod.mvec = rst_mc_vec; + + return smod; + + + + +} + +// single SNP model, required to run +size_model controller::compute_post_model_single(vector& bm){ + + + + size_model smod; + smod.size = 1; + smod.log10_sum_post = 0; + + vector post_vec; + vector abf_vec; + +// double max_log10_abf = -9999; + double max_log10_post = -9999; + int max_id = -1; + for(int index=0;index mcfg = null_config; + mcfg[index]=1; + double log10_abf = mlr.compute_log10_ABF(mcfg); + single_log10_abfv[name] = log10_abf; + abf_vec.push_back(log10_abf); + double log10_post = log10_abf + compute_log10_prior(mcfg); + post_vec.push_back(log10_post); + + if(log10_post>max_log10_post){ + max_log10_post = log10_post; + max_id = index; + } + + smod.post_map[name] = log10_post; + } + + + vector wv(post_vec.size(),1.0); + smod.log10_sum_post = mlr.log10_weighted_sum(post_vec,wv); + + double thresh = -99999; + + if(post_vec.size()>size_limit){ + vector post_vec_sort = post_vec; + sort(post_vec_sort.rbegin(), post_vec_sort.rend()); + thresh= post_vec_sort[size_limit-1]; + } + + for(int i=0;i= thresh){ + if(compute_r2(max_id,i)< ld_control_thresh) + continue; + vector mv; + mv.push_back(i); + smod.mvec.push_back(mv); + cand_set.push_back(i); + cand_map[i] = 1; + snp2cluster_map[i]=0; + } + } + + + smod.snp_cluster = cand_set; + bm.push_back(max_id); + return smod; + +} + + +size_model controller::compute_post_model(int size, int use_abs_cutoff){ + + + size_model smod; + smod.size = size; + smod.log10_sum_post = 0; + + + vector > & model_vec = szm_vec[szm_vec.size()-1].mvec; + vector > mc_vec; + + for(int i=0; i cm = model_vec[i]; + cm.push_back(cand_set[j]); + mc_vec.push_back(cm); + + } + } + + + + vector post_vec(mc_vec.size()); + int ms = mc_vec.size(); + + + + map post_map; + vector name_vec(ms); + +#pragma omp parallel for + for(int i=0;i mcfg = null_config; + vector cm = mc_vec[i]; + + string name =""; + for(int j=0;j rst_post_vec; + map rst_post_map; + vector > rst_mc_vec; + + vector post_vec_sort = post_vec; + sort(post_vec_sort.rbegin(), post_vec_sort.rend()); + + double cutoff = post_vec_sort[0] - 2; + if(!use_abs_cutoff){ + if(post_vec.size()>priority_msize){ + cutoff = post_vec_sort[priority_msize-1]; + }else{ + cutoff = post_vec_sort[post_vec_sort.size()-1]; + } + } + + for(int i=0;i= cutoff){ + rst_post_vec.push_back(post_vec[i]); + rst_mc_vec.push_back(mc_vec[i]); + rst_post_map[name_vec[i]] = post_vec[i]; + } + } + + vector wv(rst_post_vec.size(),1.0); + smod.log10_sum_post = mlr.log10_weighted_sum(rst_post_vec,wv); + smod.post_map = rst_post_map; + smod.mvec = rst_mc_vec; + return smod; + +} + + + +void controller::summarize_approx_posterior(){ + + vector log10_pmass_vec; + log10_pmass_vec.push_back(compute_log10_prior(null_config)); + + + for(int i=0;i wv1(log10_pmass_vec.size(),1.0); +// double log10_pip_NC = mlr.log10_weighted_sum(log10_pmass_vec,wv1); + + double val = log10_pmass_vec[log10_pmass_vec.size()-1]; + + double sum = 0; + double ratio = 1; + int max_model_size = szm_vec[szm_vec.size()-1].size; + if(max_size == p){ + for(int k=max_model_size+1;k<=p;k++){ + ratio *= (p-k+1)*prior_ratio/k; + sum += ratio; + } + + log10_pmass_vec.push_back(val+log10(sum)); + } + + vector wv(log10_pmass_vec.size(),1.0); + log10_pnorm = mlr.log10_weighted_sum(log10_pmass_vec,wv); + + + Nmodel nm; + nm.id = "NULL"; + nm.prob = pow(10, log10_pmass_vec[0]-log10_pnorm); + double null_prob = nm.prob; + nm.size = 0; + nm.post_score = log10_pmass_vec[0]; + nmodel_vec.push_back(nm); + + double cump = nm.prob; + + msize_mean = 0; + msize_var = 0; + + for(int i=0;i::iterator iter; + for(iter = szm_vec[i].post_map.begin(); iter != szm_vec[i].post_map.end(); iter++){ + Nmodel nm; + nm.id = iter->first; + nm.post_score = iter->second; + nm.prob = pow(10, iter->second-log10_pnorm); + nm.size = szm_vec[i].size; + if(nm.prob >= 1e-5) + nmodel_vec.push_back(nm); + parse_nmodel(nm); + + cump += nm.prob; + msize_mean += nm.prob*nm.size; + msize_var += nm.prob*pow(nm.size,2); + + } + } + + msize_var -= pow(msize_mean,2.0); + if(msize_var < 0){ + msize_var = 0; + } + + std::sort(nmodel_vec.begin(),nmodel_vec.end(),sort_nmodel_dec); + + + std::sort(nsnp_vec.begin(),nsnp_vec.end(),sort_nsnp_dec_by_ip); + + map snp2index; + for(int i=0;i member_vec; + + for(int j=0;j min_pip){ + member_vec.push_back(snp); + cluster_prob += prob; + nsnp_vec[index].cluster = cluster_index; + } + } +// if(member_vec.size()>0){ +// +// cluster_r2.push_back(compute_average_r2(member_vec)); +// cluster_count.push_back(member_vec.size()); +// cluster_pip.push_back(cluster_prob); +// cluster_id.push_back(cluster_index); +// +// if(cluster_prob >= cluster_pip_thresh){ +// grp_vec.push_back(member_vec); +// grpr2_map[cluster_count.size()-1] = grp_vec.size()-1; +// } +// cluster_index++; +// } + if(member_vec.size()>0 && cluster_prob >= cluster_pip_thresh){ + + cluster_r2.push_back(compute_average_r2(member_vec)); + cluster_count.push_back(member_vec.size()); + cluster_pip.push_back(cluster_prob); + cluster_id.push_back(cluster_index); + + grp_vec.push_back(member_vec); + grpr2_map[cluster_count.size()-1] = grp_vec.size()-1; + cluster_index++; + } + + } + + if(grp_vec.size()>1){ + + for(int i=0;i0){ + fprintf(outfd, "\nIndependent association signal clusters\n\n"); + fprintf(outfd,"\t cluster \t member_snp\t cluster_pip\t average_r2\n"); + + + for(int i=0;icounti) + id = to_string(counti)+":"+to_string(countk); + fprintf(outfd,"%7.3f\t",grp_r2[id]); + + } + fprintf(outfd,"\n"); + } + } +} + + + +void controller::parse_nmodel(Nmodel nmod){ + + istringstream iss(nmod.id); + string token; + while (getline(iss, token, '&')){ + string snp_id = token; + int index; + if(nsnp_map.find(snp_id)!=nsnp_map.end()){ + index = nsnp_map[snp_id]; + }else{ + NSNP ns; + ns.name = snp_id; + ns.incl_prob = 0; + nsnp_vec.push_back(ns); + index = nsnp_vec.size()-1; + nsnp_map[snp_id] = index; + } + nsnp_vec[index].incl_prob += nmod.prob; + + } +} + + + + + + + + +double *controller::get_weights(vector& vec){ + + double max = vec[0]; + for(int i=0;imax) + max = vec[i]; + } + double sum = 0; + for(int i=0;i mcfg = null_config; + mcfg[i] = 1; + double bhat = mlr.beta_vec[i]; + double se = mlr.se_vec[i]; + double zval = bhat/se; + + if(run_in_r==0) + fprintf(outfd,"%25s %9.3f %12.3e %12.3e %12.3e\n" , pars.geno_map[i].c_str(), mlr.compute_log10_ABF(mcfg),bhat, se, zval); + else{ + single_snp_name[i] = pars.geno_map[i]; + single_snp_bhat[i] = bhat; + single_snp_se[i] = se; + single_snp_zval[i] = zval; + single_snp_log10_ABF[i] = mlr.compute_log10_ABF(mcfg); + } + + } + + // test_scan_for_R(); + +} + +void controller::init_scan_for_R(){ + if(run_in_r>0){ + single_snp_name.resize(p); + single_snp_bhat.resize(p); + single_snp_se.resize(p); + single_snp_zval.resize(p); + single_snp_log10_ABF.resize(p); + } +} + +void controller::test_scan_for_R(){ + if(run_in_r>0){ + for(int i=0; i & vec){ + if(vec.size()==1) + return 1.0; + double sum_r2 = 0; + int count = 0; + for(int i=0;i & vec1, const vector & vec2){ + + double sum_r2 = 0; + int count = 0; + for(int i=0;i &vec, vector &wts){ + + + double max = vec[0]; + for(size_t i=0;imax) + max = vec[i]; + } + double sum = 0; + for(size_t i=0;i rhs.incl_prob; +} + + + + +bool sort_nmodel_dec(const Nmodel &lhs, const Nmodel &rhs){ + return lhs.prob > rhs.prob; +} + + diff --git a/dap_src/src/controller.h b/dap_src/src/controller.h new file mode 100644 index 0000000..a81a6f0 --- /dev/null +++ b/dap_src/src/controller.h @@ -0,0 +1,335 @@ +#include "parser.h" +#include +#include +#include "MLR.h" +#include +#include +#include +#ifdef _OPENMP +#include +#endif + +class NSNP { + + public: + + string name; + double incl_prob; + int cluster; //signal cluster membership +}; + +bool sort_nsnp_dec_by_ip(const NSNP &lhs, const NSNP &rhs); + + + +class Nmodel { + + public: + string id; + double prob; + double post_score; + int size; +}; +bool sort_nmodel_dec(const Nmodel &lhs, const Nmodel &rhs); + + + +// set of models with same size +class size_model { + + public: + int size; + double log10_sum_post; + map post_map; + vector > mvec; // models to be expanded for the next round + vector snp_cluster; +}; + + + +class controller { + + private: + + FILE *outfd; + FILE *logfd; + + parser pars; + string gene; + + vector omg2_vec; + vector kv_vec; + MLR mlr; + + int p; + + int N; + double syy; + + vector null_config; + + vector pi_vec; //prior for configs + double prior_ratio; // for estimate residual from the approximaiton + double ens; // pes or ens - expected number of signals + + + int max_size; //user option, maximum model size + + + // collection of all sizes of size_model + vector szm_vec; // size_model collections + + + //candidate set/map of SNPs + vector cand_set; // candidate SNP set for higher order models + map cand_map; + map snp2cluster_map; + + // for reporting + map nsnp_map; + + + + + // output pip for all SNPs default only output those > 0.001 + int output_all; + + + // log10 normalizing constant + double log10_pnorm; + + + + + // threshold + double snp_select_thresh; // conditional inclusion prob. + double size_select_thresh; // the decay of the posteriors of a given size + + // threshold for greedy algorithm + int size_limit; + double cluster_pip_thresh; + int priority_msize; + double log10_bf_thresh; + double ld_control_thresh; + + + // ABF options + double abf_sigma_option; + + // openmp thread + int nthread; + int use_ss; + + // run in R + int run_in_r; + + public: + // for reporting option 0 + vector nmodel_vec; + vector nsnp_vec; + double msize_mean; + double msize_var; + double min_pip; + + vector cluster_pip; + vector cluster_r2; + vector cluster_count; + vector cluster_id; + vector > grp_vec; + map grpr2_map; + map grp_r2; + map single_log10_abfv; + + // for reporting option 1 --scan + vector single_snp_name; + vector single_snp_bhat; + vector single_snp_se; + vector single_snp_zval; + vector single_snp_log10_ABF; + + // for reporting ld matrix + vector ld_matrix_flat; // flat vector of size pxp + + + // public interface + int run_option; + void initialize(char *effect_file, char *ld_file, char *grid_file, int sample_size, double syy_, int ld_format); + void initialize(char *data_file, char *grid_file); + void initialize(char *zval_file, char *ld_file, char *grid_file,int sample_size, int ld_format); + + void run(); + + void fine_map(); + void scan(); + void extract_ss(); + void extract_ss2(); + void extract_ss2_in_r(); + void print_dap_config(); + // system setting + + // options + + void set_abf_option(double sigma_option){ + abf_sigma_option= sigma_option; + } + + void set_size_limit(int size_limit_thresh){ + if(size_limit_thresh<0) + size_limit = p; + else + size_limit = size_limit_thresh; + } + + void set_ld_control(double thresh){ + ld_control_thresh = thresh; + } + + + void set_ens(double pes){ + ens = pes; + } + void set_prior(char *prior_file); + void set_prior_default(); + void set_prior(double pi1); + // for R use + void set_prior(vector& snp_names, vector prior_values); + + void set_max_size(int msize){ + max_size = msize; + } + + void set_snp_select_thresh (double thresh){ + snp_select_thresh = thresh; + } + + void set_size_select_thresh (double thresh){ + size_select_thresh = thresh; + } + + + void set_outfile(char *outfile, char *logfile); + + void set_gene(string gname){ + gene=gname; + } + + void set_output_all(){ + output_all = 1; + cluster_pip_thresh = -1; + + } + + + void set_thread(int thread){ + nthread = thread; + #ifdef _OPENMP + omp_set_num_threads(nthread); + #else + nthread=1; + #endif + } + + + // for R use + void initialize(vector& pheno, string phenoname, vector >& geno, vector& geno_name, char *grid_file, bool regress); + void initialize(vector& snp, vector& beta, vector& se, vector>& ld, int sample_size, double syy_, string phenoname); + void initialize(vector& snp, vector& zval, vector>& ld, int sample_size, string phenoname); + + void set_for_r(int quiet){ + //1:not quiet 2:quiet + run_in_r = 1 + quiet; + } + + double get_msize_mean(){ + return msize_mean; + } + + double get_msize_sd(){ + return sqrt(msize_var); + } + + double get_log10_pnorm(){ + return log10_pnorm; + } + + double get_min_pip(){ + return min_pip; + } + + int get_N(){ + return N; + } + + int get_p(){ + return p; + } + + double get_syy(){ + return syy; + } + + int get_output_all(){ + return output_all; + } + + int get_max_size(){ + return max_size; + } + + double get_ld_control_thresh(){ + return ld_control_thresh; + } + + double get_size_select_thresh(){ + return size_select_thresh; + } + + int get_nthread(){ + return nthread; + } + + string get_pheno_name(){ + return pars.pheno_name; + } + + + + + private: + + // initialization + void set_default_options(); + void load_grid(char *grid_file); + void set_default_grid(); + + void init(); + + // computing engine + double compute_log10_prior(vector& mcfg); + size_model compute_post_model_single(vector &bm); + size_model compute_post_model(int size, int use_abs_cutoff); + double conditional_est(vector &control_set); + + int backward_checking(vector& bm, double log10_post); + size_model append_post_model(int size, map &black_list); + + // reporting + void summarize_approx_posterior(); + void summary_output(); + + + // utility + void parse_nmodel(Nmodel nmod); + vector get_config(int c); + double *get_weights(vector& vec); + double compute_average_r2 (const vector & vec); + double compute_average_r2(const vector & vec1, const vector & vec2); + double compute_r2(int i, int j); + + // for R use + void init_scan_for_R(); + void test_scan_for_R(); +}; + +double log10_weighted_sum(vector &vec, vector &wts); + diff --git a/dap_src/main.cc b/dap_src/src/main.cc similarity index 96% rename from dap_src/main.cc rename to dap_src/src/main.cc index c997116..370d6f5 100644 --- a/dap_src/main.cc +++ b/dap_src/src/main.cc @@ -1,5 +1,3 @@ -using namespace std; - #include "controller.h" #include @@ -40,7 +38,7 @@ int main(int argc, char **argv){ double pes = 1.0; double pi1 = -1; - double lambda = 0.5; +// double lambda = 0.5; double ld_control = -1; int size_limit = -1; @@ -55,7 +53,7 @@ int main(int argc, char **argv){ int run_scan = 0; int extract_ss = 0; - int thread = 1; + int thread = 5; @@ -238,6 +236,9 @@ int main(int argc, char **argv){ exit(1); } + // remember to delete the following line + // con.set_for_r(0); + con.set_outfile(out_file, log_file); con.set_gene(gene_name); @@ -253,6 +254,10 @@ int main(int argc, char **argv){ con.set_max_size(msize); } + if(pes>0){ + con.set_ens(pes); + } + if(strlen(prior_file)==0){ if(pi1 != -1){ @@ -260,11 +265,11 @@ int main(int argc, char **argv){ con.set_prior(pi1); }else{ fprintf(stderr, "Warning: pi1 specification is outside the range, ignored...\n"); - con.set_prior_exp(pes); + con.set_prior_default(); } }else{ // default - con.set_prior_exp(pes); + con.set_prior_default(); } }else con.set_prior(prior_file); @@ -297,7 +302,7 @@ int main(int argc, char **argv){ con.print_dap_config(); con.run(); - return 1; + return 0; } diff --git a/dap_src/src/parser.cc b/dap_src/src/parser.cc new file mode 100644 index 0000000..276a223 --- /dev/null +++ b/dap_src/src/parser.cc @@ -0,0 +1,549 @@ +#include "parser.h" +#include "stdlib.h" +#include +#include +#include +#include +#include +#include + + +void parser::process_summary_data2(char *effect_file, char *ld_file, int sample_size, double syy, int ld_format){ + + ifstream infile(effect_file); + string line; + int counter = 0; + + while(getline(infile,line)){ + double beta; + double se; + string snp; + istringstream ins(line); + if(ins>>snp>>beta>>se){ + double var = se*se; + double z = beta/se; + double r2 = z*z/(sample_size-2+z*z); + double s2 = syy*(1-r2)/(sample_size-2.0); + double sxx = s2/var; + double sxy = beta*sxx; + geno_map[counter] = snp; + geno_rmap[snp] = counter; + + gty_vec.push_back(sxy); + sxx_vec.push_back(sxx); + + counter++; + } + } + + int p = gty_vec.size(); + ld_matrix = gsl_matrix_calloc(p,p); + ifstream infile2(ld_file); + + if(ld_format == 1){ + int row = 0; + while(getline(infile2,line)){ + stringstream ins(line); + double val; + int col = 0; + while(ins>>val){ + gsl_matrix_set(ld_matrix,row,col,val); + col++; + } + row++; + } + } + if(ld_format == 2){ + while(getline(infile2,line)){ + stringstream ins(line); + string snp1; + string snp2; + double val; + ins>>snp1>>snp2>>val; + if(geno_rmap.find(snp1) == geno_rmap.end() || geno_rmap.find(snp2) == geno_rmap.end()) + continue; + int i1 = geno_rmap[snp1]; + int i2 = geno_rmap[snp2]; + gsl_matrix_set(ld_matrix,i1,i2,val); + if(i1 != i2){ + gsl_matrix_set(ld_matrix,i2,i1,val); + } + } + + vector dvec; + vector mvec; + for(int i=0;i& snp_names, vector& beta_vector, vector& se_vector, vector>& ld, int sample_size, double syy, string name){ + pheno_name = name; + int p = snp_names.size(); + ld_matrix = gsl_matrix_calloc(p,p); + + for(int i=0; i zvec; + + while(getline(infile,line)){ + double zval; + string snp; + istringstream ins(line); + if(ins>>snp>>zval){ + geno_map[counter] = snp; + geno_rmap[snp] = counter; + // for small sample correction + if(sample_size>0){ + double h2 = zval*zval/(zval*zval+sample_size); + double factor = sqrt(0.5*(1+1/(1-h2))); + zval = zval/factor; + } + zvec.push_back(zval); + counter++; + } + } + int p = zvec.size(); + zval_matrix = gsl_matrix_calloc(p,1); + for(int i=0;i>val){ + gsl_matrix_set(ld_matrix,row,col,val); + col++; + } + row++; + } + } + + if(ld_format == 2){ + ld_matrix = gsl_matrix_calloc(p,p); + while(getline(infile2,line)){ + stringstream ins(line); + string snp1; + string snp2; + double val; + ins>>snp1>>snp2>>val; + if(geno_rmap.find(snp1) == geno_rmap.end() || geno_rmap.find(snp2) == geno_rmap.end()) + continue; + int i1 = geno_rmap[snp1]; + int i2 = geno_rmap[snp2]; + gsl_matrix_set(ld_matrix,i1,i2,val); + if(i1 != i2){ + gsl_matrix_set(ld_matrix,i2,i1,val); + } + } + + vector dvec; + vector mvec; + for(int i=0;i& snp_names, vector& z_vector, vector>& ld, int sample_size, string name){ + pheno_name = name; + int p = snp_names.size(); + + zval_matrix = gsl_matrix_calloc(p,1); + ld_matrix = gsl_matrix_calloc(p,p); + + for(int i=0; i0){ + double h2 = zval*zval/(zval*zval+sample_size); + double factor = sqrt(0.5*(1+1/(1-h2))); + zval = zval/factor; + } + gsl_matrix_set(zval_matrix,i,0,zval); + + for(int j=i; j0) + regress_cov(pheno_vec[i], covar_vec[i], geno_vec[i]); + } + // keep covar for bookkeeping + /* + for(int i=0;i0) + covar_vec[i].clear(); + } + */ +} + +void parser::process_data(vector& pheno, vector >& geno, string grp, string name, vector& geno_name, bool regress){ + // Notice: do not support multi-group! + // Does not support controlled variates for now. + + covar_vec.resize(1); + + pheno_vec.resize(1); + pheno_name = name; + pheno_vec[0] = pheno; + pheno_map[0] = grp; + pheno_index[string(grp)] = 0; + + geno_vec.resize(1); + geno_vec[0] = geno; + for(int i=0; i>header; + + string name; + string grp; + ins>> name; + ins >> grp; + + + vector vecv; + + int missing_flag = 0; // missing data flag + string val; + while(ins>>val){ + + if(val == "NA" || val == "na"){ + missing_flag = 1; + vecv.push_back(-1); + }else + vecv.push_back(atof(val.c_str())); + } + + // impute missing data with mean + + if(missing_flag == 1){ + + double nm_sum = 0; + int nm_count = 0; + vector iv; + for (int i=0;i > gvec; + geno_vec.push_back(gvec); + vector > cvec; + covar_vec.push_back(cvec); + }else if( header == "geno" || header == "covariate" ){ + int index = pheno_index[grp]; + geno_vec[index].push_back(vecv); + if(geno_rmap.find(name)==geno_rmap.end()){ + geno_map[geno_vec[index].size()-1] = name; + geno_rmap[name] = geno_vec[index].size()-1; + } + }else if(header == "controlled"){ + int index = pheno_index[grp]; + covar_vec[index].push_back(vecv); + + } + else{ + fprintf(stderr, "unknown header %s ... skipping \n", header.c_str()); + } + + + + +} + + +void parser::output(){ + + for(int i=0;i &phenov, vector > &cov, vector > &genov ){ + + int n = phenov.size(); + int p = cov.size(); + + gsl_matrix *X = gsl_matrix_calloc(n, p+1); + for(int i=0;i vec = cov[i]; + for(int j=0;j1e-8){ + gsl_matrix_set(t1,i,i,1/v); + } + } + gsl_matrix *t2 = gsl_matrix_calloc(p+1,p+1); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,V,t1,0,t2); + + gsl_matrix *XtX_inv = gsl_matrix_calloc(p+1,p+1); + gsl_blas_dgemm(CblasNoTrans,CblasTrans,1,t2,V,0,XtX_inv); + + + // (X'X)^{-1)X' + gsl_matrix *t3 = gsl_matrix_calloc(p+1,n); + gsl_blas_dgemm(CblasNoTrans,CblasTrans,1,XtX_inv,X,0,t3); + + // X(X'X)^{-1}X' + gsl_matrix *H = gsl_matrix_calloc(n,n); + gsl_blas_dgemm(CblasNoTrans,CblasNoTrans,1,X,t3,0,H); + + gsl_matrix_free(t1); + gsl_matrix_free(t2); + gsl_matrix_free(t3); + + gsl_matrix_free(XtX); + gsl_matrix_free(XtX_inv); + gsl_matrix_free(X); + + gsl_matrix_free(V); + gsl_vector_free(S); + gsl_vector_free(work); + + + // do this for all predictors and y + gsl_matrix *y = gsl_matrix_calloc(n,1); + for(int i=0;i +#include +#include +#include +#include +#include +#include +#include + +using namespace std; + +class parser { + + + public: + + vector > > geno_vec; + vector > > covar_vec; + + vector > pheno_vec; + + map pheno_map; + map pheno_index; + map geno_map; + map geno_rmap; + + string pheno_name; + + // summary level inof + gsl_matrix *zval_matrix; + gsl_matrix *ld_matrix; + vector gty_vec; + vector sxx_vec; + + void process_data(char *filename); + void process_summary_data(char *zval_file, char *ld_file, int sample_size = -1, int ld_format=1); + void process_summary_data2(char *effect_file, char *ld_file, int sample_size, double syy,int ld_format=1); + void output(); + + // for R use only + void process_data(vector& pheno, vector >& geno, string grp, string name, vector& geno_name, bool regress); + void process_summary_data2(vector& snp_names, vector& beta_vector, vector& se_vector, vector>& ld, int sample_size, double syy, string name); + void process_summary_data(vector& snp_names, vector& z_vector, vector>& ld, int sample_size, string name); + + + + private: + + void process_line(string line); + void regress_cov(vector &phenov, vector > &cov, vector > &genov ); +};