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1 from __future__ import division
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2 from collections import defaultdict
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3 import re
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4 import argparse
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5
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6 parser = argparse.ArgumentParser()
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7 parser.add_argument("--input",
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8 help="The '7_V-REGION-mutation-and-AA-change-table' and '10_V-REGION-mutation-hotspots' merged together, with an added 'best_match' annotation")
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9 parser.add_argument("--genes", help="The genes available in the 'best_match' column")
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1
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10 parser.add_argument("--empty_region_filter", help="Where does the sequence start?", choices=['leader', 'FR1', 'CDR1', 'FR2'])
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0
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11 parser.add_argument("--output", help="Output file")
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12
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13 args = parser.parse_args()
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14
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15 infile = args.input
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16 genes = str(args.genes).split(",")
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1
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17 empty_region_filter = args.empty_region_filter
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18 outfile = args.output
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19
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20 genedic = dict()
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21
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22 mutationdic = dict()
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23 mutationMatcher = re.compile("^(.)(\d+).(.),?(.)?(\d+)?.?(.)?(.?.?.?.?.?)?")
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24 NAMatchResult = (None, None, None, None, None, None, '')
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25 linecount = 0
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26
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27 IDIndex = 0
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28 best_matchIndex = 0
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29 fr1Index = 0
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30 cdr1Index = 0
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31 fr2Index = 0
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32 cdr2Index = 0
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33 fr3Index = 0
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34 first = True
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35 IDlist = []
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36 mutationList = []
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37 mutationListByID = {}
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38 cdr1LengthDic = {}
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39 cdr2LengthDic = {}
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40
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41 with open(infile, 'r') as i:
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42 for line in i:
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43 if first:
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44 linesplt = line.split("\t")
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45 IDIndex = linesplt.index("Sequence.ID")
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46 best_matchIndex = linesplt.index("best_match")
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47 fr1Index = linesplt.index("FR1.IMGT")
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48 cdr1Index = linesplt.index("CDR1.IMGT")
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49 fr2Index = linesplt.index("FR2.IMGT")
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50 cdr2Index = linesplt.index("CDR2.IMGT")
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51 fr3Index = linesplt.index("FR3.IMGT")
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52 cdr1LengthIndex = linesplt.index("CDR1.IMGT.length")
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53 cdr2LengthIndex = linesplt.index("CDR2.IMGT.length")
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54 first = False
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55 continue
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56 linecount += 1
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57 linesplt = line.split("\t")
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58 ID = linesplt[IDIndex]
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59 genedic[ID] = linesplt[best_matchIndex]
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60 try:
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1
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61 mutationdic[ID + "_FR1"] = [mutationMatcher.match(x).groups() for x in linesplt[fr1Index].split("|") if x] if (linesplt[fr1Index] != "NA" and empty_region_filter == "leader") else []
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62 mutationdic[ID + "_CDR1"] = [mutationMatcher.match(x).groups() for x in linesplt[cdr1Index].split("|") if x] if (linesplt[cdr1Index] != "NA" and empty_region_filter in ["leader", "FR1"]) else []
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63 mutationdic[ID + "_FR2"] = [mutationMatcher.match(x).groups() for x in linesplt[fr2Index].split("|") if x] if (linesplt[fr2Index] != "NA" and empty_region_filter in ["leader", "FR1", "CDR1"]) else []
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64 mutationdic[ID + "_CDR2"] = [mutationMatcher.match(x).groups() for x in linesplt[cdr2Index].split("|") if x] if (linesplt[cdr2Index] != "NA") else []
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0
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65 mutationdic[ID + "_FR2-CDR2"] = mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"]
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66 mutationdic[ID + "_FR3"] = [mutationMatcher.match(x).groups() for x in linesplt[fr3Index].split("|") if x] if linesplt[fr3Index] != "NA" else []
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1
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67 except Exception as e:
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68 print "Something went wrong while processing this line:"
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69 print linesplt
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70 print linecount
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71 print e
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72 mutationList += mutationdic[ID + "_FR1"] + mutationdic[ID + "_CDR1"] + mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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73 mutationListByID[ID] = mutationdic[ID + "_FR1"] + mutationdic[ID + "_CDR1"] + mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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74
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75 cdr1Length = linesplt[cdr1LengthIndex]
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76 cdr2Length = linesplt[cdr2LengthIndex]
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77
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78 cdr1LengthDic[ID] = int(cdr1Length) if cdr1Length != "X" else 0
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79 cdr2LengthDic[ID] = int(cdr2Length) if cdr2Length != "X" else 0
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80
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81 IDlist += [ID]
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82
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83 AALength = (int(max(mutationList, key=lambda i: int(i[4]) if i[4] else 0)[4]) + 1) # [4] is the position of the AA mutation, None if silent
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84 if AALength < 60:
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85 AALength = 64
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86
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87 AA_mutation = [0] * AALength
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3
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88 AA_mutation_dic = {"IGA": AA_mutation[:], "IGG": AA_mutation[:], "IGM": AA_mutation[:], "unm": AA_mutation[:], "all": AA_mutation[:]}
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0
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89 AA_mutation_empty = AA_mutation[:]
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90
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91 aa_mutations_by_id_file = outfile[:outfile.rindex("/")] + "/aa_id_mutations.txt"
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92 with open(aa_mutations_by_id_file, 'w') as o:
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93 o.write("ID\tbest_match\t" + "\t".join([str(x) for x in range(1,AALength)]) + "\n")
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94 for ID in mutationListByID.keys():
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95 AA_mutation_for_ID = AA_mutation_empty[:]
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96 for mutation in mutationListByID[ID]:
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97 if mutation[4]:
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98 AA_mutation_position = int(mutation[4])
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99 AA_mutation[AA_mutation_position] += 1
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100 AA_mutation_for_ID[AA_mutation_position] += 1
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101 clss = genedic[ID][:3]
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102 AA_mutation_dic[clss][AA_mutation_position] += 1
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103 o.write(ID + "\t" + genedic[ID] + "\t" + "\t".join([str(x) for x in AA_mutation_for_ID[1:]]) + "\n")
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104
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105
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106
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107 #absent AA stuff
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108 absentAACDR1Dic = defaultdict(list)
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109 absentAACDR1Dic[5] = range(29,36)
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110 absentAACDR1Dic[6] = range(29,35)
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111 absentAACDR1Dic[7] = range(30,35)
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112 absentAACDR1Dic[8] = range(30,34)
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113 absentAACDR1Dic[9] = range(31,34)
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114 absentAACDR1Dic[10] = range(31,33)
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115 absentAACDR1Dic[11] = [32]
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116
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117 absentAACDR2Dic = defaultdict(list)
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118 absentAACDR2Dic[0] = range(55,65)
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119 absentAACDR2Dic[1] = range(56,65)
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120 absentAACDR2Dic[2] = range(56,64)
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121 absentAACDR2Dic[3] = range(57,64)
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122 absentAACDR2Dic[4] = range(57,63)
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123 absentAACDR2Dic[5] = range(58,63)
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124 absentAACDR2Dic[6] = range(58,62)
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125 absentAACDR2Dic[7] = range(59,62)
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126 absentAACDR2Dic[8] = range(59,61)
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127 absentAACDR2Dic[9] = [60]
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128
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129 absentAA = [len(IDlist)] * (AALength-1)
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130 for k, cdr1Length in cdr1LengthDic.iteritems():
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131 for c in absentAACDR1Dic[cdr1Length]:
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132 absentAA[c] -= 1
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133
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134 for k, cdr2Length in cdr2LengthDic.iteritems():
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135 for c in absentAACDR2Dic[cdr2Length]:
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136 absentAA[c] -= 1
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137
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138
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139 aa_mutations_by_id_file = outfile[:outfile.rindex("/")] + "/absent_aa_id.txt"
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140 with open(aa_mutations_by_id_file, 'w') as o:
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141 o.write("ID\tcdr1length\tcdr2length\tbest_match\t" + "\t".join([str(x) for x in range(1,AALength)]) + "\n")
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142 for ID in IDlist:
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143 absentAAbyID = [1] * (AALength-1)
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144 cdr1Length = cdr1LengthDic[ID]
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145 for c in absentAACDR1Dic[cdr1Length]:
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146 absentAAbyID[c] -= 1
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147
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148 cdr2Length = cdr2LengthDic[ID]
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149 for c in absentAACDR2Dic[cdr2Length]:
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150 absentAAbyID[c] -= 1
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151 o.write(ID + "\t" + str(cdr1Length) + "\t" + str(cdr2Length) + "\t" + genedic[ID] + "\t" + "\t".join([str(x) for x in absentAAbyID]) + "\n")
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152
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153 if linecount == 0:
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154 print "No data, exiting"
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155 with open(outfile, 'w') as o:
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156 o.write("RGYW (%)," + ("0,0,0\n" * len(genes)))
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157 o.write("WRCY (%)," + ("0,0,0\n" * len(genes)))
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158 o.write("WA (%)," + ("0,0,0\n" * len(genes)))
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159 o.write("TW (%)," + ("0,0,0\n" * len(genes)))
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160 import sys
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161
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162 sys.exit()
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163
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164 hotspotMatcher = re.compile("[actg]+,(\d+)-(\d+)\((.*)\)")
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165 RGYWCount = {}
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166 WRCYCount = {}
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167 WACount = {}
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168 TWCount = {}
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169
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170 #IDIndex = 0
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171 ataIndex = 0
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172 tatIndex = 0
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173 aggctatIndex = 0
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174 atagcctIndex = 0
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175 first = True
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176 with open(infile, 'r') as i:
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177 for line in i:
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178 if first:
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179 linesplt = line.split("\t")
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180 ataIndex = linesplt.index("X.a.t.a")
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181 tatIndex = linesplt.index("t.a.t.")
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182 aggctatIndex = linesplt.index("X.a.g.g.c.t..a.t.")
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183 atagcctIndex = linesplt.index("X.a.t..a.g.c.c.t.")
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184 first = False
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185 continue
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186 linesplt = line.split("\t")
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187 gene = linesplt[best_matchIndex]
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188 ID = linesplt[IDIndex]
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189 RGYW = [(int(x), int(y), z) for (x, y, z) in
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190 [hotspotMatcher.match(x).groups() for x in linesplt[aggctatIndex].split("|") if x]]
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191 WRCY = [(int(x), int(y), z) for (x, y, z) in
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192 [hotspotMatcher.match(x).groups() for x in linesplt[atagcctIndex].split("|") if x]]
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193 WA = [(int(x), int(y), z) for (x, y, z) in
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194 [hotspotMatcher.match(x).groups() for x in linesplt[ataIndex].split("|") if x]]
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195 TW = [(int(x), int(y), z) for (x, y, z) in
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196 [hotspotMatcher.match(x).groups() for x in linesplt[tatIndex].split("|") if x]]
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197 RGYWCount[ID], WRCYCount[ID], WACount[ID], TWCount[ID] = 0, 0, 0, 0
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198
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1
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199 mutationList = mutationdic[ID + "_FR1"] + mutationdic[ID + "_CDR1"] + mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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200 for mutation in mutationList:
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201 frm, where, to, AAfrm, AAwhere, AAto, junk = mutation
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202 mutation_in_RGYW = any([(start <= int(where) <= end) for (start, end, region) in RGYW])
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203 mutation_in_WRCY = any([(start <= int(where) <= end) for (start, end, region) in WRCY])
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204 mutation_in_WA = any([(start <= int(where) <= end) for (start, end, region) in WA])
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205 mutation_in_TW = any([(start <= int(where) <= end) for (start, end, region) in TW])
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206
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207 in_how_many_motifs = sum([mutation_in_RGYW, mutation_in_WRCY, mutation_in_WA, mutation_in_TW])
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208
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209 if in_how_many_motifs > 0:
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210 RGYWCount[ID] += (1.0 * int(mutation_in_RGYW)) / in_how_many_motifs
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211 WRCYCount[ID] += (1.0 * int(mutation_in_WRCY)) / in_how_many_motifs
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212 WACount[ID] += (1.0 * int(mutation_in_WA)) / in_how_many_motifs
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213 TWCount[ID] += (1.0 * int(mutation_in_TW)) / in_how_many_motifs
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214
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215
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216 def mean(lst):
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217 return (float(sum(lst)) / len(lst)) if len(lst) > 0 else 0.0
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218
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219
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220 def median(lst):
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221 lst = sorted(lst)
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222 l = len(lst)
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223 if l == 0:
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224 return 0
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225 if l == 1:
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226 return lst[0]
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227
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228 l = int(l / 2)
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229
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230 if len(lst) % 2 == 0:
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231 return float(lst[l] + lst[(l - 1)]) / 2.0
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232 else:
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233 return lst[l]
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234
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235 funcs = {"mean": mean, "median": median, "sum": sum}
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236
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237 directory = outfile[:outfile.rfind("/") + 1]
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238 value = 0
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239 valuedic = dict()
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240
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241 for fname in funcs.keys():
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242 for gene in genes:
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243 with open(directory + gene + "_" + fname + "_value.txt", 'r') as v:
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244 valuedic[gene + "_" + fname] = float(v.readlines()[0].rstrip())
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245 with open(directory + "all_" + fname + "_value.txt", 'r') as v:
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246 valuedic["total_" + fname] = float(v.readlines()[0].rstrip())
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247
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248
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249 def get_xyz(lst, gene, f, fname):
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250 x = int(round(f(lst)))
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251 y = valuedic[gene + "_" + fname]
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252 z = str(round(x / float(y) * 100, 1)) if y != 0 else "0"
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253 return (str(x), str(y), z)
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254
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255 dic = {"RGYW": RGYWCount, "WRCY": WRCYCount, "WA": WACount, "TW": TWCount}
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256 arr = ["RGYW", "WRCY", "WA", "TW"]
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257
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258 geneMatchers = {gene: re.compile("^" + gene + ".*") for gene in genes}
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259
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260 for fname in funcs.keys():
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261 func = funcs[fname]
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262 foutfile = outfile[:outfile.rindex("/")] + "/hotspot_analysis_" + fname + ".txt"
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263 with open(foutfile, 'w') as o:
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264 for typ in arr:
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265 o.write(typ + " (%)")
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266 curr = dic[typ]
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267 for gene in genes:
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1
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268 geneMatcher = geneMatchers[gene]
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0
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269 if valuedic[gene + "_" + fname] is 0:
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270 o.write(",0,0,0")
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271 else:
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272 x, y, z = get_xyz([curr[x] for x in [y for y, z in genedic.iteritems() if geneMatcher.match(z)]], gene, func, fname)
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273 o.write("," + x + "," + y + "," + z)
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274
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275 x, y, z = get_xyz([y for x, y in curr.iteritems() if not genedic[x].startswith("unmatched")], "total", func, fname)
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276 o.write("," + x + "," + y + "," + z + "\n")
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277
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278
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279 # for testing
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280 seq_motif_file = outfile[:outfile.rindex("/")] + "/motif_per_seq.txt"
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281 with open(seq_motif_file, 'w') as o:
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282 o.write("ID\tRGYWC\tWRCY\tWA\tTW\n")
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283 for ID in IDlist:
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284 o.write(ID + "\t" + str(round(RGYWCount[ID], 2)) + "\t" + str(round(WRCYCount[ID], 2)) + "\t" + str(round(WACount[ID], 2)) + "\t" + str(round(TWCount[ID], 2)) + "\n")
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