annotate ensembl_variant_report.py @ 1:a67b4de184c2 draft

planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
author jjohnson
date Thu, 14 Jun 2018 18:08:15 -0400
parents 9f4ea174ce3d
children f87fe6bc48f4
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1 #!/usr/bin/env python
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2 """
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3 Report variants to Ensembl Transcripts
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4
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5 FrameShift report line
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6 # Gene Variant Position Reference Variation Prevalence Sequencing Depth Transcript AA Position AA change AA Length Stop Codon Stop Region AA Variation
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7 TIGD6 chr5:149374879 AAG AG 1.00 13 ENSG00000164296|ENST00000296736 345 Q344 522 A-TGA-T KRWTSSRPST*
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8
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9 MissSense report line
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10 # Gene Variant Position Reference Variation Prevalence Sequencing Depth Transcript AA Position AA change AA Length Stop Codon Stop Region AA Variation
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11 FN1 chr2:216235089 G A 1.00 7394 ENSG00000115414|ENST00000354785 2261 V2261I 2478 G-TAA TGLTRGATYN_I_IVEALKDQQR
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12 """
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13 import sys
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14 import os.path
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15 import re
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16 import time
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17 import optparse
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18 from ensemblref import EnsemblRef
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19 from Bio.Seq import reverse_complement, translate
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20
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21
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22 def __main__():
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23 #Parse Command Line
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24 parser = optparse.OptionParser()
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25 #I/O
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26 parser.add_option( '-i', '--input', dest='input', default=None, help='Tabular file with peptide_sequence column' )
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27 parser.add_option( '-s', '--format', dest='format', default='tabular', choices=['tabular','snpeff'], help='Tabular file with peptide_sequence column' )
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28 #Columns for tabular input
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29 parser.add_option( '-C', '--chrom_column', type='int', dest='chrom_column', default=1, help='column ordinal with Ensembl transctip ID' )
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30 parser.add_option( '-P', '--pos_column', type='int', dest='pos_column', default=2, help='column ordinal with Ensembl transctip ID' )
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31 parser.add_option( '-R', '--ref_column', type='int', dest='ref_column', default=3, help='column ordinal with Ensembl transctip ID' )
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32 parser.add_option( '-A', '--alt_column', type='int', dest='alt_column', default=4, help='column ordinal with Ensembl transctip ID' )
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33 parser.add_option( '-T', '--transcript_column', type='int', dest='transcript_column', default=1, help='column ordinal with Ensembl transctip ID' )
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34 parser.add_option( '-F', '--dpr_column', type='int', dest='dpr_column', default=1, help='column with VCF: DPR or AD' )
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35 parser.add_option( '-D', '--dp_column', type='int', dest='dp_column', default=1, help='column with VCF: DP' )
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36 parser.add_option( '-g', '--gene_model', dest='gene_model', default=None, help='GTF gene model file. Used to annotate NSJ peptide entries.')
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37 parser.add_option( '-2', '--twobit', dest='twobit', default=None, help='Reference genome in UCSC twobit format')
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38 #Output file
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39 parser.add_option( '-o', '--output', dest='output', default=None, help='The output report (else write to stdout)' )
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40 #filters
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41 parser.add_option( '-d', '--min_depth', type='int', dest='min_depth', default=None, help='Minimum read depth to report' )
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42 parser.add_option( '-f', '--min_freq', type='float', dest='min_freq', default=None, help='Minimum variant frequency to report' )
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43 #peptide options
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44 parser.add_option( '-l', '--leading_aa', type='int', dest='leading_aa', default=10, help='Number AAs before missense variant' )
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45 parser.add_option( '-t', '--trailing_aa', type='int', dest='trailing_aa', default=10, help='Number AAs after missense variant' )
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46 parser.add_option( '-r', '--readthrough', type='int', dest='readthrough', default=0, help='' )
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47 #
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48 parser.add_option('--debug', dest='debug', action='store_true', default=False, help='Print debugging messages')
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49 (options, args) = parser.parse_args()
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50
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51 ##INPUTS##
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52 if options.input != None:
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53 try:
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54 inputPath = os.path.abspath(options.input)
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55 inputFile = open(inputPath, 'r')
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56 except Exception, e:
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57 print >> sys.stderr, "failed: %s" % e
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58 exit(2)
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59 else:
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60 inputFile = sys.stdin
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61
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62 if options.output != None:
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63 try:
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64 outputPath = os.path.abspath(options.output)
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65 outputFile = open(outputPath, 'w')
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66 except Exception, e:
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67 print >> sys.stderr, "failed: %s" % e
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68 exit(3)
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69 else:
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70 outputFile = sys.stdout
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71
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72 def parse_tabular():
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73 ci = options.chrom_column - 1
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74 pi = options.pos_column - 1
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75 ri = options.ref_column - 1
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76 ai = options.alt_column - 1
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77 ti = options.transcript_column - 1
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78 di = options.dp_column - 1
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79 fi = options.dpr_column - 1
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80 for linenum,line in enumerate(inputFile):
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81 if options.debug:
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82 print >> sys.stderr, "%d: %s\n" % (linenum,line)
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
83 if line.startswith('#'):
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
84 continue
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
85 if line.strip() == '':
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
86 continue
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
87 fields = line.rstrip('\r\n').split('\t')
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
88 transcript = fields[ti]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
89 if not transcript:
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
90 print >> sys.stderr, "%d: %s\n" % (linenum,line)
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
91 continue
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
92 chrom = fields[ci]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
93 pos = int(fields[pi])
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
94 ref = fields[ri]
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jjohnson
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diff changeset
95 alts = fields[ai]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
96 dp = int(fields[di])
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jjohnson
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diff changeset
97 dpr = [int(x) for x in fields[fi].split(',')]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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98 for i,alt in enumerate(alts.split(',')):
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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99 freq = float(dpr[i+1])/float(sum(dpr)) if dpr else None
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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100 yield (transcript,pos,ref,alt,dp,freq)
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jjohnson
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101
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jjohnson
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102 def parse_snpeff_vcf():
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jjohnson
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103 for linenum,line in enumerate(inputFile):
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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104 if line.startswith('##'):
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jjohnson
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105 if line.find('SnpEffVersion=') > 0:
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jjohnson
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106 SnpEffVersion = re.search('SnpEffVersion="?(\d+\.\d+)',line).groups()[0]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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107 elif line.startswith('#CHROM'):
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jjohnson
parents:
diff changeset
108 pass
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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109 else:
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jjohnson
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110 fields = line.strip('\r\n').split('\t')
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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111 if options.debug: print >> sys.stderr, "\n%s" % (fields)
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
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112 (chrom, pos, id, ref, alts, qual, filter, info) = fields[0:8]
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
113 alt_list = alts.split(',')
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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114 pos = int(pos)
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jjohnson
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115 qual = float(qual)
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jjohnson
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116 dp = None
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jjohnson
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117 dpr = None
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jjohnson
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118 for info_item in info.split(';'):
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jjohnson
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119 if info_item.find('=') < 0: continue
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jjohnson
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120 (key, val) = info_item.split('=', 1)
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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121 if key == 'DP':
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jjohnson
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122 dp = int(val)
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jjohnson
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123 if key == 'DPR':
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jjohnson
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124 dpr = [int(x) for x in val.split(',')]
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jjohnson
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125 if key in ['EFF','ANN']:
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jjohnson
parents:
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126 for effect in val.split(','):
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jjohnson
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127 if options.debug: print >> sys.stderr, "\n%s" % (effect.split('|'))
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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128 if key == 'ANN':
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jjohnson
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129 (alt,eff,impact,gene_name,gene_id,feature_type,transcript,biotype,exon,c_hgvs,p_hgvs,cdna,cds,aa,distance,info) = effect.split('|')
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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130 elif key == 'EFF':
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jjohnson
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131 (eff, effs) = effect.rstrip(')').split('(')
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132 (impact, functional_class, codon_change, aa_change, aa_len, gene_name, biotype, coding, transcript, exon, alt) = effs.split('|')[0:11]
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jjohnson
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133 i = alt_list.index(alt) if alt in alt_list else 0
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jjohnson
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134 freq = float(dpr[i+1])/float(sum(dpr)) if dpr else None
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
135 yield (transcript,pos,ref,alt,dp,freq)
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jjohnson
parents:
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136
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jjohnson
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137
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jjohnson
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138 #Process gene model
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jjohnson
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139 ens_ref = None
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jjohnson
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140 if options.gene_model != None:
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jjohnson
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diff changeset
141 try:
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jjohnson
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142 geneModelFile = os.path.abspath(options.gene_model)
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jjohnson
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143 twoBitFile = os.path.abspath(options.twobit)
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jjohnson
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144 print >> sys.stderr, "Parsing ensembl ref: %s %s" % (options.gene_model,options.twobit)
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jjohnson
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145 time1 = time.time()
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jjohnson
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146 ens_ref = EnsemblRef(geneModelFile,twoBitFile)
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jjohnson
parents:
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147 time2 = time.time()
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jjohnson
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148 print >> sys.stderr, "Parsing ensembl ref: %d seconds" % (int(time2-time1))
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jjohnson
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diff changeset
149 except Exception, e:
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150 print >> sys.stderr, "Parsing gene model failed: %s" % e
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jjohnson
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diff changeset
151 exit(2)
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
152 try:
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jjohnson
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153 parse_input = parse_tabular if options.format == 'tabular' else parse_snpeff_vcf
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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154 for tid,pos1,ref,alt,dp,freq in parse_input():
1
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jjohnson
parents: 0
diff changeset
155 if options.debug: print >> sys.stderr, "%s\t%d\t%s\t%s\t%d\t%f" % (tid,pos1,ref,alt,dp,freq)
0
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jjohnson
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156 if not tid:
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
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diff changeset
157 continue
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jjohnson
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158 if options.min_depth and dp is not None and dp < options.min_depth:
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
159 continue
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jjohnson
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160 if options.min_freq and freq is not None and freq < options.min_freq:
9f4ea174ce3d planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
jjohnson
parents:
diff changeset
161 continue
1
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jjohnson
parents: 0
diff changeset
162 try:
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
parents: 0
diff changeset
163 ## transcript_id, pos, ref, alt, dp, dpr
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jjohnson
parents: 0
diff changeset
164 tx = ens_ref.get_gtf_transcript(tid)
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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diff changeset
165 if not tx and tid.find('.') > 0:
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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diff changeset
166 tid = tid.split('.')[0]
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jjohnson
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diff changeset
167 tx = ens_ref.get_gtf_transcript(tid)
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168 if not tx:
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169 continue
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170 if options.debug: print >> sys.stderr, "%s" % (tx)
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171 coding = ens_ref.transcript_is_coding(tid)
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172 if not coding:
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173 continue
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174 frame_shift = len(ref) != len(alt)
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175 cds = ens_ref.get_cds(tid)
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176 if options.debug or not cds: print >> sys.stderr, "cds:\n%s" % (cds)
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177 pos0 = pos1 - 1 # zero based position
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178 spos = pos0 if tx.gene.strand else pos0 + len(ref) - 1
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179 alt_seq = alt if tx.gene.strand else reverse_complement(alt)
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180 ref_seq = ref if tx.gene.strand else reverse_complement(ref)
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181 cds_pos = ens_ref.genome_to_cds_pos(tid, spos)
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182 if options.debug: print >> sys.stderr, "cds_pos: %s" % (str(cds_pos))
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183 alt_cds = cds[:cds_pos] + alt_seq + cds[cds_pos+len(ref):] if cds_pos+len(ref) < len(cds) else ''
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184 offset = 0
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185 if tx.gene.strand:
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186 for i in range(min(len(ref),len(alt))):
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187 if ref[i] == alt[i]:
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188 offset = i
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189 else:
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190 break
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191 else:
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192 for i in range(-1,-min(len(ref),len(alt)) -1,-1):
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193 if ref[i] == alt[i]:
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194 offset = i
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195 else:
0
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196 break
1
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197 refpep = translate(cds[:len(cds)/3*3])
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198 pep = translate(alt_cds[:len(alt_cds)/3*3])
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199 peplen = len(pep)
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200 aa_pos = (cds_pos + offset) / 3
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201 reported_stop_codon = ''
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202 if aa_pos >= len(pep):
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203 print >> sys.stderr, "aa_pos %d >= peptide length %d : %s %d %s %s" % (aa_pos,len(pep),tid,pos1,ref,alt)
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204 continue
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205 if frame_shift:
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206 #find stop_codons
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207 nstops = 0
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208 stop_codons = []
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209 for i in range(aa_pos,peplen):
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210 if refpep[i] != pep[i]:
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211 aa_pos = i
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212 break
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213 reported_peptide = pep[aa_pos:]
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214 for i in range(aa_pos,peplen):
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215 if pep[i] == '*':
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216 nstops += 1
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217 stop_codons.append("%s-%s%s" % (alt_cds[i*3-1],alt_cds[i*3:i*3+3],"-%s" % alt_cds[i*3+4] if len(alt_cds) > i*3 else ''))
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218 if nstops > options.readthrough:
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219 reported_peptide = pep[aa_pos:i+1]
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220 reported_stop_codon = ','.join(stop_codons)
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221 break
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222 else:
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223 reported_stop_codon = "%s-%s" % (alt_cds[peplen*3-4],alt_cds[peplen*3-3:peplen*3])
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224 reported_peptide = "%s_%s_%s" % (pep[max(aa_pos-options.leading_aa,0):aa_pos],
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225 pep[aa_pos],
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226 pep[aa_pos+1:min(aa_pos+1+options.trailing_aa,len(pep))])
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227 cs_pos = aa_pos * 3
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228 aa_pos = (cds_pos + offset) / 3
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229 ref_codon = cds[cs_pos:cs_pos+3]
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230 ref_aa = translate(ref_codon)
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231 alt_codon = alt_cds[cs_pos:cs_pos+3]
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232 alt_aa = translate(alt_codon)
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233 gene = tx.gene.names[0]
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234 report_fields = [tx.gene.names[0],
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235 '%s:%d %s' % (tx.gene.contig,pos1,'+' if tx.gene.strand else '-'),
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diff changeset
236 ref_seq,
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diff changeset
237 alt_seq,
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238 "%1.2f" % freq if freq is not None else '',
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diff changeset
239 str(dp),
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240 "%s|%s" % (tx.gene.gene_id,tx.cdna_id),
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241 "%d" % (aa_pos + 1),
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242 "%s%d%s" % (ref_aa,aa_pos + 1,alt_aa),
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243 "%d" % len(pep),
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diff changeset
244 reported_stop_codon,
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diff changeset
245 reported_peptide,
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diff changeset
246 tx.get_transcript_type_name()
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diff changeset
247 ]
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diff changeset
248 if options.debug:
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diff changeset
249 report_fields.append("%d %d %d %d %s %s" % (cds_pos, offset, cs_pos,aa_pos,ref_codon,alt_codon))
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diff changeset
250 outputFile.write('\t'.join(report_fields))
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251 if options.debug:
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252 print >> sys.stderr, "%s %s\n%s\n%s\n%s %s" % (
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
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253 cds[cs_pos-6:cs_pos], cds[cs_pos:cs_pos+15],
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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254 translate(cds[cs_pos-6:cs_pos+15]),
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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255 translate(alt_cds[cs_pos-6:cs_pos+15]),
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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256 alt_cds[cs_pos-6:cs_pos], alt_cds[cs_pos:cs_pos+15])
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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257 outputFile.write('\n')
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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258 except Exception, e:
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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259 print >> sys.stderr, "failed: %s" % e
a67b4de184c2 planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit b62e927469f96a857e880c77530c50c885ad92fc-dirty
jjohnson
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260 print >> sys.stderr, "%s\t%d\t%s\t%s\t%d\t%f\t%s" % (tid,pos1,ref,alt,dp,freq,e)
0
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jjohnson
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261 except Exception, e:
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jjohnson
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262 print >> sys.stderr, "failed: %s" % e
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jjohnson
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263 exit(1)
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jjohnson
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264
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jjohnson
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265
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266 if __name__ == "__main__" : __main__()
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267