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"http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "127#127" 127  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "128#128" 128  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "129#129" 129  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "130#130" 130  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "131#131" 131  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "132#132" 132  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "133#133" 133  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "134#134" 134  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "135#135" 135  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "136#136" 136  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "137#137" 137  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "138#138" 138  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "139#139" 139  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "140#140" 140  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "141#141" 141  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "142#142" 142  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "143#143" 143  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "144#144" 144  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "145#145" 145  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "146#146" 146  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "147#147" 147  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "148#148" 148  /* * Copyright (c) 2009 The Broad Institute * * Permission is hereby granted, free of charge, to any person * obtaining a copy of this software and associated documentation * files (the "Software"), to deal in the Software without * restriction, including without limitation the rights to use, * copy, modify, merge, publish, distribute, sublicense, and/or sell * copies of the Software, and to permit persons to whom the * Software is furnished to do so, subject to the following * conditions: * * The above copyright notice and this permission notice shall be * included in all copies or substantial portions of the Software. * * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, * EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES * OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND * NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT * HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, * WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING * FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR * OTHER DEALINGS IN THE SOFTWARE. */ package org.broad.tribble.util.popgen; /** * The Broad Institute * SOFTWARE COPYRIGHT NOTICE AGREEMENT * This software and its documentation are copyright 2004 by the * Broad Institute/Massachusetts Institute of Technology. All rights are reserved. * * This software is supplied without any warranty or guaranteed support whatsoever. Neither * the Broad Institute nor MIT can be responsible for its use, misuse, or functionality. */ /** * This class calculates a HardyWeinberg p-value given three values representing * the observed frequences of homozygous and heterozygous genotypes in the * test population. * * @author Bob Handsaker */ public final class HardyWeinbergCalculation { /** * This class is not instantiable. */ private HardyWeinbergCalculation() { } /** * Calculates exact two-sided hardy-weinberg p-value. Parameters * are number of genotypes, number of rare alleles observed and * number of heterozygotes observed. * * (c) 2003 Jan Wigginton, Goncalo Abecasis (goncalo@umich.edu) */ public static double hwCalculate(int obsAA, int obsAB, int obsBB) { int diplotypes = obsAA + obsAB + obsBB; int rare = (obsAA * 2) + obsAB; int hets = obsAB; //make sure "rare" allele is really the rare allele if (rare > diplotypes) { rare = (2 * diplotypes) - rare; } //make sure numbers aren't screwy if (hets > rare) { return -1; } double[] tailProbs = new double[rare + 1]; for (int z = 0; z < tailProbs.length; z++) { tailProbs[z] = 0; } //start at midpoint int mid = (rare * ((2 * diplotypes) - rare)) / (2 * diplotypes); //check to ensure that midpoint and rare alleles have same parity if (((rare & 1) ^ (mid & 1)) != 0) { mid++; } int het = mid; int hom_r = (rare - mid) / 2; int hom_c = diplotypes - het - hom_r; //Calculate probability for each possible observed heterozygote //count up to a scaling constant, to avoid underflow and overflow tailProbs[mid] = 1.0; double sum = tailProbs[mid]; for (het = mid; het > 1; het -= 2) { tailProbs[het - 2] = (tailProbs[het] * het * (het - 1.0)) / (4.0 * (hom_r + 1.0) * (hom_c + 1.0)); sum += tailProbs[het - 2]; //2 fewer hets for next iteration -> add one rare and one common homozygote hom_r++; hom_c++; } het = mid; hom_r = (rare - mid) / 2; hom_c = diplotypes - het - hom_r; for (het = mid; het <= (rare - 2); het += 2) { tailProbs[het + 2] = (tailProbs[het] * 4.0 * hom_r * hom_c) / ((het + 2.0) * (het + 1.0)); sum += tailProbs[het + 2]; //2 more hets for next iteration -> subtract one rare and one common homozygote hom_r--; hom_c--; } for (int z = 0; z < tailProbs.length; z++) { tailProbs[z] /= sum; } double top = tailProbs[hets]; for (int i = hets + 1; i <= rare; i++) { top += tailProbs[i]; } double otherSide = tailProbs[hets]; for (int i = hets - 1; i >= 0; i--) { otherSide += tailProbs[i]; } if ((top > 0.5) && (otherSide > 0.5)) { return 1.0; } if (top < otherSide) { return top * 2; } return otherSide * 2; } }  ( ) * + , - . 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