@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();
}
}
private static void addAnnotationToQTLOutput(
String in,
String inProxies,
String folderHighC,
String resolution,
String qualityCutOff,
String normMethod,
double minValue,
boolean alternativePermutation,
boolean permutationFile,
String probeMap,
String snpMap,
String out)
throws IOException {
HashMap<String, ArrayList<DesiredChrContact>> qtls =
readInQtlTransformBlocks(
in, inProxies, probeMap, snpMap, permutationFile, resolution, alternativePermutation);
ProgressBar pb =
new ProgressBar(
qtls.size(), "Checking for contacts for: " + qtls.size() + " Chromosome combinations");
TextFile outWriter = new TextFile(out, TextFile.W);
for (Entry<String, ArrayList<DesiredChrContact>> contactsToCheck : qtls.entrySet()) {
Collections.sort(contactsToCheck.getValue());
String[] chrs = contactsToCheck.getKey().split("-");
String ChrSmaller = chrs[0];
String ChrLarger = chrs[1];
String baseName;
String fileToReads;
boolean intra = false;
if (ChrSmaller.equals(ChrLarger)) {
baseName =
folderHighC
+ "\\GM12878_combined_intrachromosomal\\"
+ resolution
+ "_resolution_intrachromosomal\\chr"
+ ChrSmaller
+ "\\MAPQG"
+ qualityCutOff;
fileToReads = baseName + "\\chr" + ChrSmaller + "_" + resolution + ".RAWobserved";
intra = true;
// continue;
} else {
baseName =
folderHighC
+ "\\GM12878_combined_interchromosomal\\"
+ resolution
+ "_resolution_interchromosomal\\chr"
+ ChrSmaller
+ "_chr"
+ ChrLarger
+ "\\MAPQG"
+ qualityCutOff;
fileToReads =
baseName + "\\chr" + ChrSmaller + "_" + ChrLarger + "_" + resolution + ".RAWobserved";
}
// if (normMethod == null) {
processRawContactInformation(fileToReads, minValue, contactsToCheck.getValue(), intra);
// } else {
// if (intra) {
// processNormalizedIntraContactInformation(fileToReads, baseName,
// normMethod, ChrSmaller, contactsToCheck.getValue(), resolution, minValue, outWriter);
// } else {
// processNormalizedInterContactInformation(fileToReads, baseName,
// normMethod, ChrSmaller, ChrLarger, contactsToCheck.getValue(), resolution, minValue,
// outWriter);
// }
// }
printOutContacts(contactsToCheck.getValue(), outWriter);
pb.iterate();
}
pb.close();
outWriter.close();
}
