R/objectiveFunctions.R

In MPRAnalyze: Statistical Analysis of MPRA data

#' likelihood wrapper to compute terms of likelihood with non-zero derivative
#' with respect to case dna model and rna model 
#' 
#' @name cost.model
#' @rdname cost.model
#' 
#' @param theta vector of model parameters to evaluate likelihood for
#' (numeric, parameters)
#' @param theta.d vector of dna model parameters to condition likelihood on
#' (numeric, dna parameters)
#' @param theta.r vector of rna model parameters to condition likelihood on
#' (numeric, rna parameters)
#' @param llfnDNA cost function to compute dna likelihood terms on (function)
#' @param llfnRNA cost function to compute rna likelihood terms on (function)
#' @param dcounts the observed case DNA counts 
#' (integer, enhancers x dna samples)
#' @param rcounts the observed RNA counts (integer, enhancers x rna samples)
#' @param log.ddepth dna library size correction vector, 
#' log scale (numeric, dna samples)
#' @param log.rdepth rna library size correction vector, 
#' log scale (numeric, rna samples)
#' @param ddesign.mat the dna model design matrix 
#' (logical, dna samples x dna parameters)
#' @param rdesign.mat the rna model design matrix 
#' (logical, rna samples x rna parameters)
#' @param d2rdesign.mat the transitional design matrix, distributiong the DNA 
#' estimates to the RNA observations 
#' @param rdesign.ctrl.mat the control rna model design matrix 
#' (logical, samples x rna parameters)
#' @noRd
NULL

#' likelihood wrapper to compute terms of likelihood with non-zero derivative
#' with respect to case dna model and rna model without control enhancer
#' observations
#' 
#' nomenclature cost.[model components to be estimated]
#' 
#' Each of these function can only be called to optimise a single (enhancer) 
#' model: cost.dnarna and cost.dna can only be used on observations from one 
#' enhancer cost.rna can be used on observation from multiple enhancers under 
#' the same rna model
#' 
#' @name cost.model.noctrl
#' @rdname cost.model.noctrl
#' 
#' @aliases 
#' cost.dnarna
#' cost.dna
#' cost.rna
#' 
#' @inheritParams cost.model
#' @param rctrlscale vector of scaling parameters for rna model that correct for
#' variation between conditions pre-fit on control enhancers 
#' (numeric, ctrl rna parameters)
#' 
#' @return negative sum of log likelihood terms with non-zero derivative
#' with respect to case model 
#' @noRd
NULL

#' @rdname cost.model.noctrl
#' @noRd
cost.dnarna <- function(theta, dcounts, rcounts,
                        llfnDNA, llfnRNA,
                        log.ddepth, log.rdepth, rctrlscale=NULL,
                        ddesign.mat, rdesign.mat, d2rdesign.mat,
                        rdesign.ctrl.mat=NULL) {
    ## extract parameter vectors by model part
    # first parameter of DNA model is the variance(-link) parameter
    theta.d <- theta[seq(1, 1+NCOL(ddesign.mat), by=1)]
    theta.r <- theta[c(1, seq(1+NCOL(ddesign.mat)+1, 
                            1+NCOL(ddesign.mat)+NCOL(rdesign.mat), by=1))]
    ## compute likelihood
    # likelihood of case dna observations
    d.ll <- llfnDNA(theta = theta.d,
                    dcounts = dcounts,
                    log.ddepth = log.ddepth,
                    ddesign.mat = ddesign.mat)
    # likelihood of case rna observations
    r.ll <- llfnRNA(theta = c(theta.r, rctrlscale),
                    theta.d = matrix(theta.d),
                    rcounts = rcounts,
                    log.rdepth = log.rdepth,
                    d2rdesign.mat = d2rdesign.mat,
                    rdesign.mat = cbind(rdesign.mat, rdesign.ctrl.mat)) 

    return(d.ll + r.ll)
}

#' @rdname cost.model.noctrl
#' @noRd
cost.dna <- function(theta, theta.r,
                     llfnDNA, llfnRNA,
                     dcounts, rcounts,
                     log.ddepth, log.rdepth, rctrlscale=NULL,
                     ddesign.mat, rdesign.mat, d2rdesign.mat, 
                     rdesign.ctrl.mat=NULL) {
    
    # theta <- pmax(pmin(theta, 23), -23)
    ## compute likelihood
    d.ll <- llfnDNA(theta = theta,
                    dcounts = dcounts,
                    log.ddepth = log.ddepth,
                    ddesign.mat = ddesign.mat)
    
    r.ll <- llfnRNA(theta = c(theta.r, rctrlscale),
                    theta.d = matrix(theta),
                    rcounts = rcounts,
                    log.rdepth = log.rdepth,
                    d2rdesign.mat = d2rdesign.mat,
                    rdesign.mat = cbind(rdesign.mat, rdesign.ctrl.mat) )
    return(d.ll + r.ll)
}

#' @rdname cost.model.noctrl
#' @noRd
cost.rna <- function(theta, theta.d, llfnRNA, rcounts,
                     log.rdepth, rctrlscale=NULL,
                     d2rdesign.mat, rdesign.mat,
                     rdesign.ctrl.mat=NULL) {
    
    # theta <- pmax(pmin(theta, 23), -23)
    ## compute likelihood
    r.ll <- llfnRNA(theta = c(theta, rctrlscale),
                    theta.d = theta.d,
                    rcounts = rcounts,
                    log.rdepth = log.rdepth,
                    d2rdesign.mat = d2rdesign.mat,
                    rdesign.mat = cbind(rdesign.mat, rdesign.ctrl.mat))
    return(r.ll)
}