R/base_mosaicsZ1_1S.R

In mosaics: MOSAiCS (MOdel-based one and two Sample Analysis and Inference for ChIP-Seq)

#########################################################
# Z1 with 1 signal component
#########################################################

.mosaicsZ1_1S <- function( MOSAiCS_Z0, Y, pNfit, Y_bd_all, k=3 )
{
    ##################################################################
    ### initialization of the main EM
    ##################################################################
    
    a <- MOSAiCS_Z0$a
    #mu_est <- get_mu_est(M, GC, MOSAiCS_Z0, trunc_GC=0.55)
    mu_est <- MOSAiCS_Z0$muEst
    b_est <- a / mu_est
    pi0 <- MOSAiCS_Z0$pi0
    tab_Y <- MOSAiCS_Z0$Y_freq
    Y_u <- MOSAiCS_Z0$Y_val
    
    
    # initial mu & var

    mu1_init <- mean(Y_bd_all)
    var1_init <- var(Y_bd_all)
    
    
    # calculate initial EN and varN, based on initial mu & var

    EN <- mean(mu_est)
    varN <- EN*( 1 + EN/a ) 

    if( mu1_init < EN )
    {
        EN <- mu1_init - 0.1
    }

    if( var1_init < varN )
    {
        varN <- var1_init - 0.15
    }
    
    
    # initialize b & c

    if( var1_init - varN - mu1_init + EN <= 0 )
    {
        b_init <- (mu1_init - EN)^2 / 0.1
        c_init <- (mu1_init - EN) / 0.1   
    } else
    {
        b_init <- (mu1_init - EN)^2 / (var1_init - varN - mu1_init + EN)
        c_init <- (mu1_init - EN) / (var1_init - varN - mu1_init + EN)    
    }  


    ##################################################################
    ### The main EM calculation: iterate till convergence
    ##################################################################
    
    #print( "initialization for EM" )
    
    # calculate EN and vanN
    # (redefine EN after heuristic EN adjustment for initialization)

    EN <- mean(mu_est)
    varN <- EN*(1 + EN/a) 
    
    
    # parameters for Y>=k
    
    id_geqk <- which(Y>=k)
    Y_ori <- Y[id_geqk]
    Y_Z1 <- Y - k               # adjusted Y
    Y_Z1 <- Y_Z1[id_geqk]
    #M_Z1 <- M[id_geqk]
    #GC_Z1 <- GC[id_geqk]
    b_est_Z1 <- b_est[id_geqk]
    mu_est_Z1 <- mu_est[id_geqk]
    
    Yk <- Y_ori - k        # use only Y >= k
    #if(length(which(Y<0))>0 ) Y[which(Y<0)] <- -1 
    Ykmax <- max(Yk)
    #ind_ge_k <- which(Y>=0)
    
    
    # Initialization of the main EM calculation
    
    #PYZ0 <- dnbinom( Y_ori, a, b_est_Z1/(b_est_Z1+1) )
    PYZ0 <- pNfit$PYZ0
    #pNfit <- .calcPN( Y_ori, k, a, mu_est_Z1 ) 
    #PYZ1 <- .margDistZ1_1S( Y_ori, pNfit, b_init, c_init )
    PYZ1 <- .margDistZ1_1S( Yk, Ykmax, pNfit, b_init, c_init )

    b_iter <- b_init
    c_iter <- c_init
    
    
    # main EM iteration

    eps <- 1e-6
    #logLik <- -Inf
    #logLik <- c(logLik, sum(log(pi0*PYZ0 + (1-pi0)*PYZ1)))
    logLik1 <- sum( log( pi0*PYZ0 + (1-pi0)*PYZ1 ) )
    logLik <- c( -Inf, logLik1 )
    iter <- 2
    
    #print( "simulation" )
    
    while( abs(logLik[iter]-logLik[iter-1])>eps & iter < 10 )
    {
        # E-step
        
        Z_latent <- (1 - pi0)*PYZ1 / ( pi0*PYZ0 + (1 - pi0)*PYZ1 )
        
        # M-step
        
        mu1 <- sum(Z_latent*Y_Z1) / sum(Z_latent)
        var1 <- sum(Z_latent*(Y_Z1 - mu1)^2) / sum(Z_latent)

        b <- (mu1 - EN)^2 / (var1 - varN - mu1 + EN)
        c <- (mu1 - EN) / (var1 - varN - mu1 + EN)
        
        # stop iteration if assumptions are not satisfied
        
        if ( b<0 | c<0 )
        {
            b <- b_iter[(iter-1)]
            c <- c_iter[(iter-1)]
            break
        }
        
        # calculate P(Y|Z=1)
        
        #print( "calculate P(Y|Z=1)" )
        
        #PYZ1 <- .margDistZ1_1S( Y_ori, pNfit, b, c )
        PYZ1 <- .margDistZ1_1S( Yk, Ykmax, pNfit, b, c )
        
        # update iteration
        
        #logLik <- c(logLik, sum(log(pi0*PYZ0 + (1-pi0)*PYZ1)))
        logLik_t <- sum( log( pi0*PYZ0 + (1-pi0)*PYZ1 ) )
        if ( is.na(logLik_t) | is.nan(logLik_t) ) {
            b <- b_iter[(iter-1)]
            c <- c_iter[(iter-1)]
            logLik_t <- logLik[(iter-1)]
            break
        }
        logLik <- c( logLik, logLik_t )
        b_iter <- c(b_iter, b)
        c_iter <- c(c_iter, c)

        iter <- iter + 1
    }
    

    #return(list(M_u = MOSAiCS_Z0$M_u, GC_u = MOSAiCS_Z0$GC_u, a_u = MOSAiCS_Z0$a_u, b_u = MOSAiCS_Z0$b_u, mean0_u = MOSAiCS_Z0$mean0_u, var0_u = MOSAiCS_Z0$var0_u, u0_u = MOSAiCS_Z0$u0_u, u1_u = MOSAiCS_Z0$u1_u, u2_u = MOSAiCS_Z0$u2_u, n_u = MOSAiCS_Z0$n_u, ty_u = MOSAiCS_Z0$ty_u, Y_val = MOSAiCS_Z0$Y_val, Y_freq = MOSAiCS_Z0$Y_freq, pi0 = MOSAiCS_Z0$pi0, a = MOSAiCS_Z0$a, beta0_strata = MOSAiCS_Z0$beta0_strata, betaM_strata = MOSAiCS_Z0$betaM_strata, betaM2_strata = MOSAiCS_Z0$betaM2_strata, betaGC_strata = MOSAiCS_Z0$betaGC_strata, b = b, c = c, b_init = b_init, c_init = c_init, logLik = logLik, b_iter = b_iter, c_iter = c_iter))
    
    #return( list( 
    #    M_u = MOSAiCS_Z0$M_u, GC_u = MOSAiCS_Z0$GC_u, a_u = MOSAiCS_Z0$a_u, b_u = MOSAiCS_Z0$b_u,
    #    mean0_u = MOSAiCS_Z0$mean0_u, var0_u = MOSAiCS_Z0$var0_u, n_u = MOSAiCS_Z0$n_u, ty_u = MOSAiCS_Z0$ty_u,
    #    Y_val = MOSAiCS_Z0$Y_val, Y_freq = MOSAiCS_Z0$Y_freq,
    #    pi0 = MOSAiCS_Z0$pi0, a = MOSAiCS_Z0$a, b = b, c = c,
    #    mu_est = mu_est ) )
    
    return( list( 
        pi0 = MOSAiCS_Z0$pi0, a = MOSAiCS_Z0$a, muEst = MOSAiCS_Z0$muEst,
        b = b, c = c ) )
}

#.margDistZ1_1S <- function( Yori, pNfit, b, c )
.margDistZ1_1S <- function( Y, Ymax, pNfit, b, c )
{     
    k <- pNfit$k
    pN <- pNfit$pN
    mu_round <- pNfit$mu_round
    mu_round_U <- pNfit$mu_round_U
    
    # process Y
    
    #Y <- Yori - k        # use only Y >= k
    #if(length(which(Y<0))>0 ) Y[which(Y<0)] <- -1 
    #Ymax <- max(Y)
    #ind_ge_k <- which(Y>=0)
    
    # prob of S    
    
    pS <- dnbinom( 0:Ymax, b, c/(c+1) )   
    #MDZ1 <- rep( 0, length(Y) )            
    #MDZ1[ ind_ge_k ] <- conv_1S( y=Y[ind_ge_k], mu_round=mu_round[ind_ge_k],
    #    mu_round_U=mu_round_U, pN=pN, pS=pS )
    MDZ1 <- conv_1S( y=Y, mu_round=mu_round,
        mu_round_U=mu_round_U, pN=pN, pS=pS )
    
    return(MDZ1)   
}