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"http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "124#124" 124  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "125#125" 125  HYPERLINK "http://code.google.com/p/tribble/source/browse/trunk/src/org/broad/tribble/util/popgen/HardyWeinbergCalculation.java?r=3" \l "126#126" 126  HYPERLINK "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;� � �}� }�  �������( ) * + , - . � � � � � � � R S T U V W X � � � � � � � | } ~  � � �        � � � � � � � ; < = > ��̵�����ൢ����ൢ����ൢ����ൢ����ൢ����ൢ����ൢ����ൢ���$hr�hr�CJKHOJQJ^JaJ-jhr�hr�CJKHOJQJU^JaJ'hr�hr�<�CJKHOJQJ^JaJhr�hr�CJKHaJ$hr�hr�CJKHOJQJ^JaJ@��, ����M�5kdj$IfK$L$�h���6��������4�a�($ �2�(� P�x �4 �#\'�*�.2�5@9$1$Ifa$gdr�Ekd$IfK$L$�� �� ������6��������4�a�p� ����$$1$Ifa$gdr�K$�s�, - � � V W � ����N�5kdK$IfK$L$�h���6��������4�a�5kd$IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd�$IfK$L$�h���6��������4�a�� � � �   � ����N�5kd,$IfK$L$�h���6��������4�a�5kd�$IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd�$IfK$L$�h���6��������4�a�� � ? 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@ A � � � � � � � j!k!m!�������������������������������������������������������������������������������hr�hr�CJKHaJ$hr�hr�CJKHOJQJ^JaJ-jhr�hr�CJKHOJQJU^JaJO��������N�5kd $IfK$L$�h���6��������4�a�5kd� $IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd $IfK$L$�h���6��������4�a���GH��w����N�5kd� $IfK$L$�h���6��������4�a�5kd� $IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd` $IfK$L$�h���6��������4�a�wx��? ����N�5kd� $IfK$L$�h���6��������4�a�5kd� $IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kdA $IfK$L$�h���6��������4�a�? @ � � o!p!"����N�5kd� $IfK$L$�h���6��������4�a�5kdm $IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd" $IfK$L$�h���6��������4�a�m!n!o!p!q!"""""" "�"�"�"�"�"�"�"2#3#5#6#7#8#9#�#�#�#�#�#�#�#b$c$e$f$g$h$i$�$�$�$�$�$%%�%�%�%�%�%�%�%*&+&-&.&/&0&1&�&�&�&�&�&�&�&Z'[']'^'_'`'a'�'�'�'�'�'�������������������������������������������������������������������������������hr�hr�CJKHaJ$hr�hr�CJKHOJQJ^JaJ-jhr�hr�CJKHOJQJU^JaJO""�"�"7#8#�#����N�5kd� $IfK$L$�h���6��������4�a�5kdN $IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd $IfK$L$�h���6��������4�a��#�#g$h$�$%�%����N�5kdz$IfK$L$�h���6��������4�a�5kd/$IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd� $IfK$L$�h���6��������4�a��%�%/&0&�&�&_'����N�5kd[$IfK$L$�h���6��������4�a�5kd$IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd�$IfK$L$�h���6��������4�a�_'`'�'�'�(�(')����N�5kd<$IfK$L$�h���6��������4�a�5kd�$IfK$L$�h���6��������4�a�$$1$Ifa$gdr�K$5kd�$IfK$L$�h���6��������4�a��'�'�'�(�(�(�(�(�(�(")#)%)&)')()))�)�)�)�)�)�)�)R*S*U*V*W*X*Y*�*�*�*�*�*�*�*�+�+�+�+�+�+�+,,,,, 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