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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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10 parser.add_argument("--includefr1", help="Should the mutation/nucleotides in the FR1 region be included?")
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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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17 print "includefr1 =", args.includefr1
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18 include_fr1 = True if args.includefr1 == "yes" else False
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19 outfile = args.output
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20
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21 genedic = dict()
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22
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23 mutationdic = dict()
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24 mutationMatcher = re.compile("^(.)(\d+).(.),?(.)?(\d+)?.?(.)?(.?.?.?.?.?)?")
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25 NAMatchResult = (None, None, None, None, None, None, '')
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26 linecount = 0
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27
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28 IDIndex = 0
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29 best_matchIndex = 0
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30 fr1Index = 0
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31 cdr1Index = 0
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32 fr2Index = 0
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33 cdr2Index = 0
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34 fr3Index = 0
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35 first = True
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36 IDlist = []
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37 mutationList = []
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38 mutationListByID = {}
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39 cdr1LengthDic = {}
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40 cdr2LengthDic = {}
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41
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42 with open(infile, 'r') as i:
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43 for line in i:
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44 if first:
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45 linesplt = line.split("\t")
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46 IDIndex = linesplt.index("Sequence.ID")
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47 best_matchIndex = linesplt.index("best_match")
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48 fr1Index = linesplt.index("FR1.IMGT")
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49 cdr1Index = linesplt.index("CDR1.IMGT")
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50 fr2Index = linesplt.index("FR2.IMGT")
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51 cdr2Index = linesplt.index("CDR2.IMGT")
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52 fr3Index = linesplt.index("FR3.IMGT")
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53 cdr1LengthIndex = linesplt.index("CDR1.IMGT.length")
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54 cdr2LengthIndex = linesplt.index("CDR2.IMGT.length")
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55 first = False
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56 continue
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57 linecount += 1
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58 linesplt = line.split("\t")
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59 ID = linesplt[IDIndex]
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60 genedic[ID] = linesplt[best_matchIndex]
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61 try:
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62 if linesplt[fr1Index] != "NA":
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63 mutationdic[ID + "_FR1"] = [mutationMatcher.match(x).groups() for x in linesplt[fr1Index].split("|") if x] if include_fr1 else []
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64 else:
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65 mutationdic[ID + "_FR1"] = []
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66 mutationdic[ID + "_CDR1"] = [mutationMatcher.match(x).groups() for x in linesplt[cdr1Index].split("|") if x] if linesplt[cdr1Index] != "NA" else []
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67 mutationdic[ID + "_FR2"] = [mutationMatcher.match(x).groups() for x in linesplt[fr2Index].split("|") if x] if linesplt[fr2Index] != "NA" else []
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68 mutationdic[ID + "_CDR2"] = [mutationMatcher.match(x).groups() for x in linesplt[cdr2Index].split("|") if x] if linesplt[cdr2Index] != "NA" else []
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69 mutationdic[ID + "_FR2-CDR2"] = mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"]
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70 mutationdic[ID + "_FR3"] = [mutationMatcher.match(x).groups() for x in linesplt[fr3Index].split("|") if x] if linesplt[fr3Index] != "NA" else []
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71 except e:
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72 print linesplt
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73 print linecount
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74 print e
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75 mutationList += mutationdic[ID + "_FR1"] + mutationdic[ID + "_CDR1"] + mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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76 mutationListByID[ID] = mutationdic[ID + "_FR1"] + mutationdic[ID + "_CDR1"] + mutationdic[ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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77
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78 cdr1Length = linesplt[cdr1LengthIndex]
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79 cdr2Length = linesplt[cdr2LengthIndex]
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80
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81 cdr1LengthDic[ID] = int(cdr1Length) if cdr1Length != "X" else 0
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82 cdr2LengthDic[ID] = int(cdr2Length) if cdr2Length != "X" else 0
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83
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84 IDlist += [ID]
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85
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86 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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87 if AALength < 60:
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88 AALength = 64
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89
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90 AA_mutation = [0] * AALength
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91 AA_mutation_dic = {"IGA": AA_mutation[:], "IGG": AA_mutation[:], "IGM": AA_mutation[:], "unm": AA_mutation[:]}
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92 AA_mutation_empty = AA_mutation[:]
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93
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94 aa_mutations_by_id_file = outfile[:outfile.rindex("/")] + "/aa_id_mutations.txt"
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95 with open(aa_mutations_by_id_file, 'w') as o:
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96 o.write("ID\tbest_match\t" + "\t".join([str(x) for x in range(1,AALength)]) + "\n")
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97 for ID in mutationListByID.keys():
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98 AA_mutation_for_ID = AA_mutation_empty[:]
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99 for mutation in mutationListByID[ID]:
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100 if mutation[4]:
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101 AA_mutation_position = int(mutation[4])
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102 AA_mutation[AA_mutation_position] += 1
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103 AA_mutation_for_ID[AA_mutation_position] += 1
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104 clss = genedic[ID][:3]
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105 AA_mutation_dic[clss][AA_mutation_position] += 1
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106 o.write(ID + "\t" + genedic[ID] + "\t" + "\t".join([str(x) for x in AA_mutation_for_ID[1:]]) + "\n")
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107
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108
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109
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110 #absent AA stuff
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111 absentAACDR1Dic = defaultdict(list)
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112 absentAACDR1Dic[5] = range(29,36)
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113 absentAACDR1Dic[6] = range(29,35)
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114 absentAACDR1Dic[7] = range(30,35)
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115 absentAACDR1Dic[8] = range(30,34)
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116 absentAACDR1Dic[9] = range(31,34)
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117 absentAACDR1Dic[10] = range(31,33)
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118 absentAACDR1Dic[11] = [32]
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119
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120 absentAACDR2Dic = defaultdict(list)
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121 absentAACDR2Dic[0] = range(55,65)
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122 absentAACDR2Dic[1] = range(56,65)
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123 absentAACDR2Dic[2] = range(56,64)
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124 absentAACDR2Dic[3] = range(57,64)
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125 absentAACDR2Dic[4] = range(57,63)
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126 absentAACDR2Dic[5] = range(58,63)
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127 absentAACDR2Dic[6] = range(58,62)
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128 absentAACDR2Dic[7] = range(59,62)
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129 absentAACDR2Dic[8] = range(59,61)
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130 absentAACDR2Dic[9] = [60]
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131
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132 absentAA = [len(IDlist)] * (AALength-1)
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133 for k, cdr1Length in cdr1LengthDic.iteritems():
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134 for c in absentAACDR1Dic[cdr1Length]:
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135 absentAA[c] -= 1
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136
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137 for k, cdr2Length in cdr2LengthDic.iteritems():
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138 for c in absentAACDR2Dic[cdr2Length]:
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139 absentAA[c] -= 1
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140
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141
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142 aa_mutations_by_id_file = outfile[:outfile.rindex("/")] + "/absent_aa_id.txt"
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143 with open(aa_mutations_by_id_file, 'w') as o:
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144 o.write("ID\tcdr1length\tcdr2length\tbest_match\t" + "\t".join([str(x) for x in range(1,AALength)]) + "\n")
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145 for ID in IDlist:
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146 absentAAbyID = [1] * (AALength-1)
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147 cdr1Length = cdr1LengthDic[ID]
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148 for c in absentAACDR1Dic[cdr1Length]:
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149 absentAAbyID[c] -= 1
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150
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151 cdr2Length = cdr2LengthDic[ID]
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152 for c in absentAACDR2Dic[cdr2Length]:
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153 absentAAbyID[c] -= 1
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154 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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155
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156 if linecount == 0:
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157 print "No data, exiting"
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158 with open(outfile, 'w') as o:
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159 o.write("RGYW (%)," + ("0,0,0\n" * len(genes)))
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160 o.write("WRCY (%)," + ("0,0,0\n" * len(genes)))
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161 o.write("WA (%)," + ("0,0,0\n" * len(genes)))
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162 o.write("TW (%)," + ("0,0,0\n" * len(genes)))
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163 import sys
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164
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165 sys.exit()
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166
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167 hotspotMatcher = re.compile("[actg]+,(\d+)-(\d+)\((.*)\)")
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168 RGYWCount = {}
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169 WRCYCount = {}
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170 WACount = {}
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171 TWCount = {}
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172
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173 #IDIndex = 0
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174 ataIndex = 0
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175 tatIndex = 0
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176 aggctatIndex = 0
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177 atagcctIndex = 0
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178 first = True
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179 with open(infile, 'r') as i:
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180 for line in i:
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181 if first:
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182 linesplt = line.split("\t")
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183 ataIndex = linesplt.index("X.a.t.a")
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184 tatIndex = linesplt.index("t.a.t.")
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185 aggctatIndex = linesplt.index("X.a.g.g.c.t..a.t.")
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186 atagcctIndex = linesplt.index("X.a.t..a.g.c.c.t.")
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187 first = False
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188 continue
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189 linesplt = line.split("\t")
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190 gene = linesplt[best_matchIndex]
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191 ID = linesplt[IDIndex]
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192 if ID == "ca2":
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193 print linesplt
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194 RGYW = [(int(x), int(y), z) for (x, y, z) in
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195 [hotspotMatcher.match(x).groups() for x in linesplt[aggctatIndex].split("|") if x]]
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196 WRCY = [(int(x), int(y), z) for (x, y, z) in
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197 [hotspotMatcher.match(x).groups() for x in linesplt[atagcctIndex].split("|") if x]]
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198 WA = [(int(x), int(y), z) for (x, y, z) in
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199 [hotspotMatcher.match(x).groups() for x in linesplt[ataIndex].split("|") if x]]
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200 TW = [(int(x), int(y), z) for (x, y, z) in
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201 [hotspotMatcher.match(x).groups() for x in linesplt[tatIndex].split("|") if x]]
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202 RGYWCount[ID], WRCYCount[ID], WACount[ID], TWCount[ID] = 0, 0, 0, 0
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203
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204 mutationList = (mutationdic[ID + "_FR1"] if include_fr1 else []) + mutationdic[ID + "_CDR1"] + mutationdic[
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205 ID + "_FR2"] + mutationdic[ID + "_CDR2"] + mutationdic[ID + "_FR3"]
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206 for mutation in mutationList:
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207 frm, where, to, AAfrm, AAwhere, AAto, junk = mutation
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208 mutation_in_RGYW = any([(start <= int(where) <= end) for (start, end, region) in RGYW])
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209 mutation_in_WRCY = any([(start <= int(where) <= end) for (start, end, region) in WRCY])
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210 mutation_in_WA = any([(start <= int(where) <= end) for (start, end, region) in WA])
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211 mutation_in_TW = any([(start <= int(where) <= end) for (start, end, region) in TW])
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212
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213 in_how_many_motifs = sum([mutation_in_RGYW, mutation_in_WRCY, mutation_in_WA, mutation_in_TW])
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214
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215 if in_how_many_motifs > 0:
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216 RGYWCount[ID] += (1.0 * int(mutation_in_RGYW)) / in_how_many_motifs
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217 WRCYCount[ID] += (1.0 * int(mutation_in_WRCY)) / in_how_many_motifs
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218 WACount[ID] += (1.0 * int(mutation_in_WA)) / in_how_many_motifs
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219 TWCount[ID] += (1.0 * int(mutation_in_TW)) / in_how_many_motifs
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220
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221
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222 def mean(lst):
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223 return (float(sum(lst)) / len(lst)) if len(lst) > 0 else 0.0
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224
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225
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226 def median(lst):
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227 lst = sorted(lst)
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228 l = len(lst)
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229 if l == 0:
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230 return 0
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231 if l == 1:
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232 return lst[0]
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233
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234 l = int(l / 2)
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235
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236 if len(lst) % 2 == 0:
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237 return float(lst[l] + lst[(l - 1)]) / 2.0
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238 else:
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239 return lst[l]
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240
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241 funcs = {"mean": mean, "median": median, "sum": sum}
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242
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243 directory = outfile[:outfile.rfind("/") + 1]
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244 value = 0
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245 valuedic = dict()
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246
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247 for fname in funcs.keys():
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248 for gene in genes:
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249 with open(directory + gene + "_" + fname + "_value.txt", 'r') as v:
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250 valuedic[gene + "_" + fname] = float(v.readlines()[0].rstrip())
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251 with open(directory + "all_" + fname + "_value.txt", 'r') as v:
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252 valuedic["total_" + fname] = float(v.readlines()[0].rstrip())
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253
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254
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255 def get_xyz(lst, gene, f, fname):
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256 x = int(round(f(lst)))
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257 y = valuedic[gene + "_" + fname]
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258 z = str(round(x / float(y) * 100, 1)) if y != 0 else "0"
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259 return (str(x), str(y), z)
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260
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261 dic = {"RGYW": RGYWCount, "WRCY": WRCYCount, "WA": WACount, "TW": TWCount}
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262 arr = ["RGYW", "WRCY", "WA", "TW"]
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263
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264 geneMatchers = {gene: re.compile("^" + gene + ".*") for gene in genes}
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265
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266 for fname in funcs.keys():
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267 func = funcs[fname]
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268 foutfile = outfile[:outfile.rindex("/")] + "/hotspot_analysis_" + fname + ".txt"
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269 with open(foutfile, 'w') as o:
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270 for typ in arr:
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271 o.write(typ + " (%)")
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272 curr = dic[typ]
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273 for gene in genes:
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274 geneMatcher = geneMatchers[gene] #re.compile("^" + gene + ".*") #recompile every loop....
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275 if valuedic[gene + "_" + fname] is 0:
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276 o.write(",0,0,0")
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277 else:
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278 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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279 o.write("," + x + "," + y + "," + z)
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280
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281 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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282 o.write("," + x + "," + y + "," + z + "\n")
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283
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284
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285 # for testing
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286 seq_motif_file = outfile[:outfile.rindex("/")] + "/motif_per_seq.txt"
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287 with open(seq_motif_file, 'w') as o:
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288 o.write("ID\tRGYWC\tWRCY\tWA\tTW\n")
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289 for ID in IDlist:
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290 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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