test_that("Check genotype generation.", { withr::local_seed(101) # Minor allele count is always positive. g <- GenGenoMat(n = 100, snps = 1e3) mac <- apply(g, 2, sum) expect_gte(min(mac), 1) # Number of alternate alleles never exceeds 2. g <- GenGenoMat(n = 100, snps = 1e3, maf_range = c(0.5, 1.0)) max_g <- max(g) expect_lte(max_g, 2) # Minor allele frequency is near the expected range. # MAF is not expected to fall exactly within the rage due to stochasticity. n <- 1e3 g <- GenGenoMat(n = n, snps = 1e2, maf_range = c(0.001, 0.005)) maf <- apply(g, 2, mean) / 2 expect_gte(min(maf), 1 / (2 * n)) expect_lte(max(maf), 2 * 0.005) }) # ------------------------------------------------------------------------------ test_that("Check annotation generation.", { withr::local_seed(101) anno <- GenAnno(1000) expect_true(all(anno %in% c(1, 2, 3))) anno <- GenAnno(1000, prop_anno = c(1, 1, 1, 1)) expect_true(all(anno %in% c(1, 2, 3, 4))) }) # ------------------------------------------------------------------------------ test_that("Check phenotype generation.", { # Test cases without aggregation. anno <- c(1, 2, 3) geno <- rbind( c(0, 0, 0), c(2, 0, 0), c(0, 2, 0), c(0, 0, 2) ) covar <- c(rep(1, 4)) beta <- c(1, 2, 4) reg_param <- list(coef = as.matrix(0)) weights <- c(1, 1, 1) # Counts. obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, weights = weights ) exp <- c(0, 2 * 1, 2 * 2, 2 * 4) expect_true(all(obs == exp)) # Indicators. obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = TRUE, weights = weights ) exp <- c(0, 1 * 1, 1 * 2, 1 * 4) expect_true(all(obs == exp)) # Random signs. withr::local_seed(101) obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, random_signs = TRUE, weights = weights ) exp <- c(0, 2 * -1, 2 * -2, 2 * 4) expect_true(all(obs == exp)) # Binary phenotype. withr::local_seed(101) obs <- GenPheno( anno = anno, beta = beta, binary = TRUE, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, random_signs = TRUE, weights = weights ) exp <- 1 * (c(0, 2 * -1, 2 * -2, 2 * 4) >= 0) expect_true(all(obs == exp)) # Test cases with aggregation. # Genotypes for aggregation methods. anno <- c(1, 2, 3) geno <- rbind( c(0, 0, 0), c(1, 1, 1), c(0, 2, 0), c(1, 0, 2) ) weights <- c(0, 1, 2) # Sum aggregation. beta <- 1.0 obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, method = "sum", weights = weights ) exp <- c(0, 1 * 1 + 1 * 2, 2 * 1, 2 * 2) expect_equal(obs, exp) # Max aggregation. beta <- 1.0 obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, method = "max", weights = weights ) exp <- c(0, 2, 2, 4) expect_equal(obs, exp) # Check case of more than 3 annotation categories. anno <- c(1, 2, 3, 4) geno <- rbind( c(0, 0, 0, 0), c(2, 0, 0, 0), c(0, 2, 0, 0), c(0, 0, 2, 0), c(0, 0, 0, 2) ) covar <- c(rep(1, 5)) beta <- c(1, 2, 4, 8) reg_param <- list(coef = as.matrix(0)) weights <- c(1, 1, 1, 1) # Counts. obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, weights = weights ) exp <- c(0, 2 * 1, 2 * 2, 2 * 4, 2 * 8) expect_true(all(obs == exp)) # Indicators. obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = TRUE, weights = weights ) exp <- c(0, 1 * 1, 1 * 2, 1 * 4, 1 * 8) expect_true(all(obs == exp)) # Genotypes for aggregation. geno <- rbind( c(0, 0, 0, 0), c(1, 0, 0, 0), c(0, 1, 0, 0), c(1, 0, 1, 0), c(0, 1, 0, 1) ) weights <- c(1, 2, 3, 4) # Sum aggregation. beta <- 1.0 obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, method = "sum", weights = weights ) exp <- c(0, 1, 2, 1 + 3, 2 + 4) expect_equal(obs, exp) # Max aggregation. obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, indicator = FALSE, method = "max", weights = weights ) exp <- c(0, 1, 2, 3, 4) expect_equal(obs, exp) # Check incompatible settings. # Random signs cannot be used with aggregated genotypes. expect_error( obs <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, random_signs = TRUE, method = "max" ) ) }) # ------------------------------------------------------------------------------ test_that("Check data generation with manual phenotypes.", { # Annotations and genotypes both provided. anno <- c(1, 2, 3) geno <- rbind( c(0, 0, 0), c(1, 1, 1), c(0, 2, 0), c(1, 0, 2) ) data <- DGP(anno = anno, geno = geno) expect_true(all(data$anno == anno)) expect_true(all(data$geno == geno)) # Only annotations provided. data <- DGP(anno = anno, n = 10, snps = 10) expect_true(all(data$anno == anno)) expect_true(ncol(data$geno) == length(anno)) # snps replaced by length(anno). # Only genotypes provided. data <- DGP(geno = geno, n = 10, snps = 10) expect_true(all(data$geno == geno)) expect_true(length(data$pheno) == nrow(geno)) # n replaced by nrow(geno). expect_true(length(data$anno) == ncol(geno)) # snps replaced by ncol(geno). }) # ------------------------------------------------------------------------------ test_that("Check ability to vary the proportion of causal variants.", { anno <- c(1, 2, 3) geno <- rbind( c(0, 0, 0), c(1, 1, 1), c(0, 2, 0), c(1, 0, 2) ) covar <- c(rep(1, 4)) beta <- c(1, 2, 3) reg_param <- list(coef = as.matrix(0)) weights <- c(1, 1, 1) # Setting the causal proportion to zero results in no genetic component. null_pheno <- GenPheno( anno = anno, beta = beta, geno = geno, covar = covar, reg_param = reg_param, include_residual = FALSE, prop_causal = 0.0 ) expect_true(all(null_pheno == 0)) # Generate phenotypes 2 ways: # 1. Filtering genotypes externally. # 2. Filtering genotypes internally. withr::local_seed(1010) filtered_geno <- FilterGenos(anno = anno, geno = geno, prop_causal = 1/3) external_pheno <- GenPheno( anno = filtered_geno$anno, beta = beta, geno = filtered_geno$geno, covar = covar, reg_param = reg_param, include_residual = FALSE, prop_causal = 1.0 ) withr::local_seed(1010) internal_pheno <- GenPheno( anno = anno, beta = beta, geno = geno, covar = covar, reg_param = reg_param, include_residual = FALSE, prop_causal = 1/3 ) expect_equal(external_pheno, internal_pheno) }) # ------------------------------------------------------------------------------ test_that( "Checking ability to generate phenotypes with random genetic effects.", { anno <- c(1, 2, 3) geno <- rbind( c(0, 0, 0), c(1, 1, 1), c(0, 2, 0), c(1, 0, 2) ) covar <- c(rep(1, 4)) beta <- c(1, 2, 3) reg_param <- list(coef = as.matrix(0)) weights <- c(1, 1, 1) withr::local_seed(123) y_nonrandom <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, random_signs = TRUE, random_var = 0.0 ) withr::local_seed(123) y_random <- GenPheno( anno = anno, beta = beta, covar = covar, geno = geno, reg_param = reg_param, include_residual = FALSE, random_signs = TRUE, random_var = 1.0 ) expect_gt(stats::var(y_random), stats::var(y_nonrandom)) }) # ------------------------------------------------------------------------------ test_that("Check sumstats generation.", { withr::local_seed(123) anno <- c(1, 2, 3) n <- 100 geno <- replicate(3, stats::rbinom(n = n, size = 2, prob = 0.25)) pheno <- stats::rnorm(n = n) covar <- rep(1, n) # Calculate sumstats manually. ld <- cor(geno) sumstats <- lapply(seq_len(3), function(i) { fit <- stats::lm(pheno ~ geno[, i]) results <- summary(fit) beta <- as.numeric(results$coefficients[, "Estimate"][2]) se <- as.numeric(results$coefficients[, "Std. Error"][2]) return(data.frame(beta = beta, se = se)) }) sumstats <- do.call(rbind, sumstats) # Check function outputs. data <- list( anno = anno, geno = geno, pheno = pheno, covar = covar, type = "quantitative" ) obs <- CalcSumstats(data = data) expect_equal(ld, obs$ld, tolerance = 1e-4) expect_equal(sumstats$beta, obs$sumstats$beta, tolerance = 1e-4) expect_equal(sumstats$se, obs$sumstats$se, tolerance = 1e-4) }) # ------------------------------------------------------------------------------ test_that("Test sumstat generation when covariates are omitted.", { withr::local_seed(123) data <- DGP() # Method 1: No covariates provided. sumstats1 <- CalcSumstats( anno = data$anno, geno = data$geno, pheno = data$pheno ) # Method 2: Provide intercept for covariates. sumstats2 <- CalcSumstats( anno = data$anno, covar = rep(1, length(data$pheno)), geno = data$geno, pheno = data$pheno ) expect_equal(sumstats1$sumstats, sumstats2$sumstats) }) # ------------------------------------------------------------------------------ test_that( "Expect error when the number of annotation categories is inconsistent.", { # Fewer weights than annotation categories. expect_error( data <- DGP( prop_anno = c(1, 1, 1, 1), weights = c(1, 2, 3) ) ) # Fewer betas than annotation categories. expect_error( data <- DGP( beta = c(1, 2, 3), prop_anno = c(1, 1, 1, 1), weights = c(1, 2, 3, 4) ) ) # Expect no error because parameters are consistent. expect_error( data <- DGP( beta = c(1, 2, 3, 4), prop_anno = c(1, 1, 1, 1), weights = c(1, 2, 3, 4) ), NA) # Expect no error because aggregation is applied. expect_error( data <- DGP( beta = 1, prop_anno = c(1, 1, 1, 1), method = "sum", weights = c(1, 2, 3, 4) ), NA) })