@Override public void run() throws IOException { for (int d = 0; d < m_gg.length; d++) { // now test all triples SNPLoader snpLoader = m_gg[d].getGenotypeData().createSNPLoader(); int[] indWGA = m_gg[d].getExpressionToGenotypeIdArray(); for (int perm = 0; perm < m_settings.nrPermutationsFDR + 1; perm++) { String outfile = null; if (perm == 0) { outfile = outDir + m_gg[d].getSettings().name + "_IVAnalysis-RealData.txt"; } else { outfile = outDir + m_gg[d].getSettings().name + "_IVAnalysis-PermutationRound-" + perm + ".txt"; m_gg[d].permuteSampleLables(); } TextFile out = new TextFile(outfile, TextFile.W); Iterator<Triple<String, String, String>> it = snpProbeCombos.iterator(); Triple<String, String, String> next = it.next(); ProgressBar pb = new ProgressBar( snpProbeCombos.size(), "Running Mediation Analysis - Permutation " + perm); out.writeln( "SNP\tSNP Chr\tSNP ChrPos\t" + "Alleles\tDirectionAllele\t" + "N\t" + "CisArrayAddress\tCisProbe Chr\tCisProbe ChrPos\t" + "CisGeneName\t" + "TransArrayAddress\tTransProbe Chr\tTransProbe ChrPos\t" + "TransGeneName\t" + "CisTrans-Correlation\t" + "Cis-eQTL-Beta\t" + "Cis-eQTL-SE\t" + "CisTrans-Beta\t" + "CisTrans-SE\t" + "Trans-eQTL-Beta\t" + "Trans-eQTL-SE\t" + "CisTrans-Residual-Correlation\t" + "CisTrans-Residual-Beta\t" + "CisTrans-Residual-SE\t" + "Trans-eQTL-Residual-Beta\t" + "Trans-eQTL-Residual-SE\t" + "Beta-Ratio"); while (next != null) { String snp = next.getLeft(); String cisprobe = next.getMiddle(); String transprobe = next.getRight(); Integer snpId = m_gg[d].getGenotypeData().getSnpToSNPId().get(snp); Integer cisProbeId = m_gg[d].getExpressionData().getProbeToId().get(cisprobe); Integer transProbeId = m_gg[d].getExpressionData().getProbeToId().get(transprobe); if (snpId == -9 || cisProbeId == null || transProbeId == null) { // out.writeln(snp + "\t" + snpId + "\t" + cisprobe + "\t" + // cisProbeId + "\t" + null + "\t" + transprobe + "\t" + transProbeId + "\t" + null + // "\t" + null + "\t" + null + "\t" + null + "\t" + null + // "\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA"); } else { SNP snpObj = m_gg[d].getGenotypeData().getSNPObject(snpId); snpLoader.loadGenotypes(snpObj); if (snpLoader.hasDosageInformation()) { snpLoader.loadDosage(snpObj); } double[] origCisVals = m_gg[d].getExpressionData().getMatrix()[cisProbeId]; double[] origTransVals = m_gg[d].getExpressionData().getMatrix()[transProbeId]; int calledGenotypes = 0; for (int i = 0; i < m_gg[d].getExpressionData().getIndividuals().length; i++) { int genotypeId = indWGA[i]; short gt = snpObj.getGenotypes()[genotypeId]; if (genotypeId > -1 && gt > -1) { calledGenotypes++; } } double[] genotypes = new double[calledGenotypes]; double[] cisvals = new double[calledGenotypes]; double[] transvals = new double[calledGenotypes]; calledGenotypes = 0; for (int i = 0; i < m_gg[d].getExpressionData().getIndividuals().length; i++) { int genotypeId = indWGA[i]; short gt = snpObj.getGenotypes()[genotypeId]; if (genotypeId > -1 && gt > -1) { genotypes[calledGenotypes] = snpObj.getDosageValues()[genotypeId]; cisvals[calledGenotypes] = origCisVals[i]; transvals[calledGenotypes] = origTransVals[i]; calledGenotypes++; } } // normalize genotype and cis + trans to get beta's equal to the correlation coefficient genotypes = normalize(genotypes); cisvals = normalize(cisvals); transvals = normalize(transvals); double corrCisTrans = JSci.maths.ArrayMath.correlation(cisvals, transvals); // for code validation double[] cisTransRCs = Regression.getLinearRegressionCoefficients( cisvals, transvals); // returns beta, alpha, se, t double[] snpCisRCs = Regression.getLinearRegressionCoefficients( genotypes, cisvals); // returns beta, alpha, se, t double[] snpTransRCs = Regression.getLinearRegressionCoefficients(genotypes, transvals); // remove correlation between cis and trans probe // double[] resCis = new double[cisvals.length]; double[] resTransVals = new double[cisvals.length]; for (int i = 0; i < resTransVals.length; i++) { // resCis[i] = cisvals[i] - snpCisRCs[0] * genotypes[i]; resTransVals[i] = transvals[i] - cisTransRCs[0] * cisvals[i]; } resTransVals = normalize(resTransVals); double[] cisResTransRCs = Regression.getLinearRegressionCoefficients( cisvals, resTransVals); // returns beta, alpha, se, t double[] snpResTransRCs = Regression.getLinearRegressionCoefficients(genotypes, resTransVals); double rescorr = JSci.maths.ArrayMath.correlation(cisvals, resTransVals); // for code validation out.writeln( snp + "\t" + snpObj.getChr() + "\t" + snpObj.getChrPos() + "\t" + BaseAnnot.toString(snpObj.getAlleles()[0]) + "/" + BaseAnnot.toString(snpObj.getAlleles()[1]) + "\t" + BaseAnnot.toString(snpObj.getAlleles()[0]) + "\t" + transvals.length + "\t" + cisprobe + "\t" + m_gg[d].getExpressionData().getChr()[cisProbeId] + "\t" + m_gg[d].getExpressionData().getChrStart()[cisProbeId] + ":" + m_gg[d].getExpressionData().getChrStop()[cisProbeId] + "\t" + m_gg[d].getExpressionData().getAnnotation()[cisProbeId] + "\t" + transprobe + "\t" + m_gg[d].getExpressionData().getChr()[transProbeId] + "\t" + m_gg[d].getExpressionData().getChrStart()[transProbeId] + ":" + m_gg[d].getExpressionData().getChrStop()[transProbeId] + "\t" + m_gg[d].getExpressionData().getAnnotation()[transProbeId] + "\t" + corrCisTrans + "\t" + snpCisRCs[0] + "\t" + snpCisRCs[2] + "\t" + cisTransRCs[0] + "\t" + cisTransRCs[2] + "\t" + snpTransRCs[0] + "\t" + snpTransRCs[2] + "\t" + rescorr + "\t" + cisResTransRCs[0] + "\t" + cisResTransRCs[2] + "\t" + snpResTransRCs[0] + "\t" + snpResTransRCs[2] + "\t" + (snpResTransRCs[0] / snpTransRCs[0])); snpObj.clearGenotypes(); } if (it.hasNext()) { next = it.next(); } else { next = null; } pb.iterate(); } pb.close(); out.close(); } snpLoader.close(); } }