1 | #!/usr/bin/python2.6 |
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2 | |
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3 | import sys |
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4 | |
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5 | import bx.align.maf |
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6 | import bx.bitset |
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7 | from bx.bitset_builders import * |
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8 | from itertools import * |
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9 | from optparse import OptionParser |
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10 | from rpy import * |
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11 | |
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12 | def main(): |
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13 | |
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14 | # Parse the command line |
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15 | parser = OptionParser(usage = "usage: %prog [options] maf_file snp_file neutral_file window_size step_size") |
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16 | |
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17 | parser.add_option("-o", "--outfile", help = "Specify file for output") |
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18 | |
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19 | parser.add_option("-s", "--species", type = "string", default = "panTro2") |
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20 | |
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21 | parser.add_option("-b", "--build", type = "string", default = "hg18") |
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22 | |
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23 | (options, args) = parser.parse_args() |
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24 | |
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25 | if len(args) != 5: |
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26 | parser.error("Incorrect number of arguments") |
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27 | else: |
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28 | maf_filename = args[0] |
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29 | snp_filename = args[1] |
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30 | neutral_filename = args[2] |
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31 | window_size = int(args[3]) |
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32 | step_size = int(args[4]) |
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33 | |
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34 | if options.outfile != None: |
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35 | out_file = open(options.outfile, 'w') |
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36 | |
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37 | #Generate snp and neutral bitsets |
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38 | AR_snp_bitsets = binned_bitsets_from_file(open(snp_filename)) |
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39 | neutral_bitsets = binned_bitsets_from_file(open(neutral_filename)) |
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40 | |
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41 | # Generate divergence bitset from maf file |
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42 | AR_div_bitsets = dict() |
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43 | chr_lens = dict() |
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44 | reader = bx.align.maf.Reader( open (maf_filename) ) |
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45 | |
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46 | for block in reader: |
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47 | comp1 = block.get_component_by_src_start( options.build ) |
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48 | comp2 = block.get_component_by_src_start( options.species ) |
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49 | |
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50 | if comp1 is None or comp2 is None: |
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51 | continue |
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52 | |
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53 | # Chromosome, start, and stop of reference species alignment |
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54 | chr = comp1.src.split( '.' )[1] |
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55 | start = comp1.start |
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56 | end = comp1.end |
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57 | |
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58 | # Get or create bitset for this chromosome |
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59 | if chr in AR_div_bitsets: |
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60 | bitset = AR_div_bitsets[chr] |
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61 | else: |
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62 | bitset = AR_div_bitsets[chr] = bx.bitset.BinnedBitSet() |
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63 | chr_lens[chr] = comp1.get_src_size() |
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64 | |
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65 | # Iterate over text and set diverged bit |
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66 | pos = start |
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67 | for ch1, ch2 in izip( comp1.text.upper(), comp2.text.upper() ): |
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68 | if ch1 == '-': continue |
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69 | if ch2 == '-': |
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70 | pos += 1 |
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71 | continue |
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72 | |
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73 | if ch1 != ch2 and not AR_snp_bitsets[chr][pos]: |
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74 | bitset.set( pos ) |
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75 | pos += 1 |
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76 | |
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77 | # Debugging Code |
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78 | # for chr in AR_div_bitsets: |
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79 | # for pos in range(0, AR_div_bitsets[chr].size): |
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80 | # if AR_div_bitsets[pos]: |
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81 | # print >> sys.stderr, chr, pos, pos+1 |
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82 | |
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83 | # Copy div and snp bitsets |
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84 | nonAR_snp_bitsets = dict() |
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85 | for chr in AR_snp_bitsets: |
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86 | nonAR_snp_bitsets[chr] = bx.bitset.BinnedBitSet() |
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87 | nonAR_snp_bitsets[chr].ior(AR_snp_bitsets[chr]) |
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88 | |
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89 | nonAR_div_bitsets = dict() |
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90 | for chr in AR_div_bitsets: |
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91 | nonAR_div_bitsets[chr] = bx.bitset.BinnedBitSet() |
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92 | nonAR_div_bitsets[chr].ior(AR_div_bitsets[chr]) |
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93 | |
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94 | # Generates AR snps by intersecting with neutral intervals |
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95 | for chr in AR_snp_bitsets: |
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96 | AR_snp_bitsets[chr].iand(neutral_bitsets[chr]) |
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97 | |
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98 | # Generates AR divs by intersecting with neutral intervals |
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99 | for chr in AR_div_bitsets: |
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100 | AR_div_bitsets[chr].iand(neutral_bitsets[chr]) |
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101 | |
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102 | # Inverts the neutral intervals so now represents nonAR |
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103 | for chr in neutral_bitsets: |
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104 | neutral_bitsets[chr].invert() |
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105 | |
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106 | # Generates nonAR snps by intersecting with masked neutral intervals |
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107 | for chr in nonAR_snp_bitsets: |
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108 | nonAR_snp_bitsets[chr].iand(neutral_bitsets[chr]) |
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109 | # Generates nonAR divs by intersecting with masked neutral intervals |
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110 | for chr in nonAR_div_bitsets: |
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111 | nonAR_div_bitsets[chr].iand(neutral_bitsets[chr]) |
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112 | |
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113 | for chr in AR_div_bitsets: |
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114 | for window in range(0, chr_lens[chr] - window_size, step_size): |
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115 | # neutral_size = neutral_bitsets[chr].count_range(window, window_size) |
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116 | # if neutral_size < 9200: continue |
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117 | AR_snp = AR_snp_bitsets[chr].count_range(window, window_size) |
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118 | AR_div = AR_div_bitsets[chr].count_range(window, window_size) |
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119 | nonAR_snp = nonAR_snp_bitsets[chr].count_range(window, window_size) |
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120 | nonAR_div = nonAR_div_bitsets[chr].count_range(window, window_size) |
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121 | |
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122 | if nonAR_snp >= 6 and nonAR_div >= 6 and AR_snp >= 6 and AR_div >= 6: |
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123 | MK_pval = MK_chi_pvalue(nonAR_snp, nonAR_div, AR_snp, AR_div) |
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124 | else: |
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125 | MK_pval = MK_fisher_pvalue(nonAR_snp, nonAR_div, AR_snp, AR_div) |
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126 | |
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127 | if options.outfile != None: |
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128 | out_file.write("%s\t%d\t%d\t%d\t%d\t%d\t%d\t%1.15f\n" % (chr, window, window+window_size, nonAR_snp, nonAR_div, AR_snp, AR_div, MK_pval)) |
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129 | else: |
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130 | print "%s\t%d\t%d\t%d\t%d\t%d\t%d\t%1.15f" % (chr, window, window+window_size, nonAR_snp, nonAR_div, AR_snp, AR_div, MK_pval) |
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131 | |
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132 | if options.outfile != None: |
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133 | out_file.close() |
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134 | |
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135 | def MK_fisher_pvalue(win_snp, win_div, AR_snp, AR_div): |
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136 | |
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137 | if win_snp == 0 and win_div == 0 and AR_snp == 0 and AR_div == 0: |
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138 | return 1.0 |
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139 | |
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140 | fisher_result = r.fisher_test(r.matrix(r.c([win_snp, win_div, AR_snp, AR_div]), nr = 2)) |
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141 | |
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142 | return fisher_result['p.value'] |
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143 | |
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144 | def MK_chi_pvalue(win_snp, win_div, AR_snp, AR_div): |
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145 | |
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146 | chi_result = r.chisq_test(r.matrix(r.c([win_snp, win_div, AR_snp, AR_div]), nr = 2)) |
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147 | |
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148 | return chi_result['p.value'] |
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149 | |
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150 | main() |
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