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comparison ensembl_variant_report.py @ 0:9f4ea174ce3d draft

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planemo upload for repository https://github.com/jj-umn/galaxytools/tree/master/ensembl_variant_report commit e6aa05bbbee3cc7d98f16354fc41c674f439ff1b-dirty
author jjohnson
date Thu, 14 Jun 2018 17:51:39 -0400
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children a67b4de184c2
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-1:000000000000 0:9f4ea174ce3d
1 #!/usr/bin/env python
2 """
3 Report variants to Ensembl Transcripts
4
5 FrameShift report line
6 # Gene Variant Position Reference Variation Prevalence Sequencing Depth Transcript AA Position AA change AA Length Stop Codon Stop Region AA Variation
7 TIGD6 chr5:149374879 AAG AG 1.00 13 ENSG00000164296|ENST00000296736 345 Q344 522 A-TGA-T KRWTSSRPST*
8
9 MissSense report line
10 # Gene Variant Position Reference Variation Prevalence Sequencing Depth Transcript AA Position AA change AA Length Stop Codon Stop Region AA Variation
11 FN1 chr2:216235089 G A 1.00 7394 ENSG00000115414|ENST00000354785 2261 V2261I 2478 G-TAA TGLTRGATYN_I_IVEALKDQQR
12 """
13 import sys
14 import os.path
15 import re
16 import time
17 import optparse
18 from ensemblref import EnsemblRef
19 from Bio.Seq import reverse_complement, translate
20
21
22 def __main__():
23 #Parse Command Line
24 parser = optparse.OptionParser()
25 #I/O
26 parser.add_option( '-i', '--input', dest='input', default=None, help='Tabular file with peptide_sequence column' )
27 parser.add_option( '-s', '--format', dest='format', default='tabular', choices=['tabular','snpeff'], help='Tabular file with peptide_sequence column' )
28 #Columns for tabular input
29 parser.add_option( '-C', '--chrom_column', type='int', dest='chrom_column', default=1, help='column ordinal with Ensembl transctip ID' )
30 parser.add_option( '-P', '--pos_column', type='int', dest='pos_column', default=2, help='column ordinal with Ensembl transctip ID' )
31 parser.add_option( '-R', '--ref_column', type='int', dest='ref_column', default=3, help='column ordinal with Ensembl transctip ID' )
32 parser.add_option( '-A', '--alt_column', type='int', dest='alt_column', default=4, help='column ordinal with Ensembl transctip ID' )
33 parser.add_option( '-T', '--transcript_column', type='int', dest='transcript_column', default=1, help='column ordinal with Ensembl transctip ID' )
34 parser.add_option( '-F', '--dpr_column', type='int', dest='dpr_column', default=1, help='column with VCF: DPR or AD' )
35 parser.add_option( '-D', '--dp_column', type='int', dest='dp_column', default=1, help='column with VCF: DP' )
36 parser.add_option( '-g', '--gene_model', dest='gene_model', default=None, help='GTF gene model file. Used to annotate NSJ peptide entries.')
37 parser.add_option( '-2', '--twobit', dest='twobit', default=None, help='Reference genome in UCSC twobit format')
38 #Output file
39 parser.add_option( '-o', '--output', dest='output', default=None, help='The output report (else write to stdout)' )
40 #filters
41 parser.add_option( '-d', '--min_depth', type='int', dest='min_depth', default=None, help='Minimum read depth to report' )
42 parser.add_option( '-f', '--min_freq', type='float', dest='min_freq', default=None, help='Minimum variant frequency to report' )
43 #peptide options
44 parser.add_option( '-l', '--leading_aa', type='int', dest='leading_aa', default=10, help='Number AAs before missense variant' )
45 parser.add_option( '-t', '--trailing_aa', type='int', dest='trailing_aa', default=10, help='Number AAs after missense variant' )
46 parser.add_option( '-r', '--readthrough', type='int', dest='readthrough', default=0, help='' )
47 #
48 parser.add_option('--debug', dest='debug', action='store_true', default=False, help='Print debugging messages')
49 (options, args) = parser.parse_args()
50
51 ##INPUTS##
52 if options.input != None:
53 try:
54 inputPath = os.path.abspath(options.input)
55 inputFile = open(inputPath, 'r')
56 except Exception, e:
57 print >> sys.stderr, "failed: %s" % e
58 exit(2)
59 else:
60 inputFile = sys.stdin
61
62 if options.output != None:
63 try:
64 outputPath = os.path.abspath(options.output)
65 outputFile = open(outputPath, 'w')
66 except Exception, e:
67 print >> sys.stderr, "failed: %s" % e
68 exit(3)
69 else:
70 outputFile = sys.stdout
71
72 def parse_tabular():
73 ci = options.chrom_column - 1
74 pi = options.pos_column - 1
75 ri = options.ref_column - 1
76 ai = options.alt_column - 1
77 ti = options.transcript_column - 1
78 di = options.dp_column - 1
79 fi = options.dpr_column - 1
80 for linenum,line in enumerate(inputFile):
81 if options.debug:
82 print >> sys.stderr, "%d: %s\n" % (linenum,line)
83 if line.startswith('#'):
84 continue
85 if line.strip() == '':
86 continue
87 fields = line.rstrip('\r\n').split('\t')
88 transcript = fields[ti]
89 if not transcript:
90 print >> sys.stderr, "%d: %s\n" % (linenum,line)
91 continue
92 chrom = fields[ci]
93 pos = int(fields[pi])
94 ref = fields[ri]
95 alts = fields[ai]
96 dp = int(fields[di])
97 dpr = [int(x) for x in fields[fi].split(',')]
98 for i,alt in enumerate(alts.split(',')):
99 freq = float(dpr[i+1])/float(sum(dpr)) if dpr else None
100 yield (transcript,pos,ref,alt,dp,freq)
101
102 def parse_snpeff_vcf():
103 for linenum,line in enumerate(inputFile):
104 if line.startswith('##'):
105 if line.find('SnpEffVersion=') > 0:
106 SnpEffVersion = re.search('SnpEffVersion="?(\d+\.\d+)',line).groups()[0]
107 elif line.startswith('#CHROM'):
108 pass
109 else:
110 fields = line.strip('\r\n').split('\t')
111 if options.debug: print >> sys.stderr, "\n%s" % (fields)
112 (chrom, pos, id, ref, alts, qual, filter, info) = fields[0:8]
113 alt_list = alts.split(',')
114 pos = int(pos)
115 qual = float(qual)
116 dp = None
117 dpr = None
118 for info_item in info.split(';'):
119 if info_item.find('=') < 0: continue
120 (key, val) = info_item.split('=', 1)
121 if key == 'DP':
122 dp = int(val)
123 if key == 'DPR':
124 dpr = [int(x) for x in val.split(',')]
125 if key in ['EFF','ANN']:
126 for effect in val.split(','):
127 if options.debug: print >> sys.stderr, "\n%s" % (effect.split('|'))
128 if key == 'ANN':
129 (alt,eff,impact,gene_name,gene_id,feature_type,transcript,biotype,exon,c_hgvs,p_hgvs,cdna,cds,aa,distance,info) = effect.split('|')
130 elif key == 'EFF':
131 (eff, effs) = effect.rstrip(')').split('(')
132 (impact, functional_class, codon_change, aa_change, aa_len, gene_name, biotype, coding, transcript, exon, alt) = effs.split('|')[0:11]
133 i = alt_list.index(alt) if alt in alt_list else 0
134 freq = float(dpr[i+1])/float(sum(dpr)) if dpr else None
135 yield (transcript,pos,ref,alt,dp,freq)
136
137
138 #Process gene model
139 ens_ref = None
140 if options.gene_model != None:
141 try:
142 geneModelFile = os.path.abspath(options.gene_model)
143 twoBitFile = os.path.abspath(options.twobit)
144 print >> sys.stderr, "Parsing ensembl ref: %s %s" % (options.gene_model,options.twobit)
145 time1 = time.time()
146 ens_ref = EnsemblRef(geneModelFile,twoBitFile)
147 time2 = time.time()
148 print >> sys.stderr, "Parsing ensembl ref: %d seconds" % (int(time2-time1))
149 except Exception, e:
150 print >> sys.stderr, "Parsing gene model failed: %s" % e
151 exit(2)
152 try:
153 parse_input = parse_tabular if options.format == 'tabular' else parse_snpeff_vcf
154 for tid,pos1,ref,alt,dp,freq in parse_input():
155 if not tid:
156 continue
157 if options.min_depth and dp is not None and dp < options.min_depth:
158 continue
159 if options.min_freq and freq is not None and freq < options.min_freq:
160 continue
161 ## transcript_id, pos, ref, alt, dp, dpr
162 tx = ens_ref.get_gtf_transcript(tid)
163 if not tx:
164 continue
165 coding = ens_ref.transcript_is_coding(tid)
166 if not coding:
167 continue
168 frame_shift = len(ref) != len(alt)
169 cds = ens_ref.get_cds(tid)
170 pos0 = pos1 - 1 # zero based position
171 spos = pos0 if tx.gene.strand else pos0 + len(ref) - 1
172 alt_seq = alt if tx.gene.strand else reverse_complement(alt)
173 ref_seq = ref if tx.gene.strand else reverse_complement(ref)
174 cds_pos = ens_ref.genome_to_cds_pos(tid, spos)
175 alt_cds = cds[:cds_pos] + alt_seq + cds[cds_pos+len(ref):] if cds_pos+len(ref) < len(cds) else ''
176 offset = 0
177 if tx.gene.strand:
178 for i in range(min(len(ref),len(alt))):
179 if ref[i] == alt[i]:
180 offset = i
181 else:
182 break
183 else:
184 for i in range(-1,-min(len(ref),len(alt)) -1,-1):
185 if ref[i] == alt[i]:
186 offset = i
187 else:
188 break
189 refpep = translate(cds[:len(cds)/3*3])
190 pep = translate(alt_cds[:len(alt_cds)/3*3])
191 peplen = len(pep)
192 aa_pos = (cds_pos + offset) / 3
193 if aa_pos >= len(pep):
194 print >> sys.stderr, "aa_pos %d >= peptide length %d : %s %d %s %s\n" % (aa_pos,len(pep),tid,pos1,ref,alt)
195 continue
196 if frame_shift:
197 #find stop_codons
198 nstops = 0
199 stop_codons = []
200 for i in range(aa_pos,peplen):
201 if refpep[i] != pep[i]:
202 aa_pos = i
203 break
204 for i in range(aa_pos,peplen):
205 if pep[i] == '*':
206 nstops += 1
207 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 ''))
208 if nstops > options.readthrough:
209 reported_peptide = pep[aa_pos:i+1]
210 reported_stop_codon = ','.join(stop_codons)
211 break
212 else:
213 reported_stop_codon = "%s-%s" % (alt_cds[peplen*3-4],alt_cds[peplen*3-3:peplen*3])
214 reported_peptide = "%s_%s_%s" % (pep[max(aa_pos-options.leading_aa,0):aa_pos],
215 pep[aa_pos],
216 pep[aa_pos+1:min(aa_pos+1+options.trailing_aa,len(pep))])
217 cs_pos = aa_pos * 3
218 aa_pos = (cds_pos + offset) / 3
219 ref_codon = cds[cs_pos:cs_pos+3]
220 ref_aa = translate(ref_codon)
221 alt_codon = alt_cds[cs_pos:cs_pos+3]
222 alt_aa = translate(alt_codon)
223 gene = tx.gene.names[0]
224 report_fields = [tx.gene.names[0],
225 '%s:%d %s' % (tx.gene.contig,pos1,'+' if tx.gene.strand else '-'),
226 ref_seq,
227 alt_seq,
228 "%1.2f" % freq if freq is not None else '',
229 str(dp),
230 "%s|%s" % (tx.gene.gene_id,tx.cdna_id),
231 "%d" % (aa_pos + 1),
232 "%s%d%s" % (ref_aa,aa_pos + 1,alt_aa),
233 "%d" % len(pep),
234 reported_stop_codon,
235 reported_peptide
236 ]
237 if options.debug:
238 report_fields.append("%d %d %d %d %s %s" % (cds_pos, offset, cs_pos,aa_pos,ref_codon,alt_codon))
239 outputFile.write('\t'.join(report_fields))
240 if options.debug:
241 print >> sys.stderr, "%s %s\n%s\n%s\n%s %s" % (
242 cds[cs_pos-6:cs_pos], cds[cs_pos:cs_pos+15],
243 translate(cds[cs_pos-6:cs_pos+15]),
244 translate(alt_cds[cs_pos-6:cs_pos+15]),
245 alt_cds[cs_pos-6:cs_pos], alt_cds[cs_pos:cs_pos+15])
246 outputFile.write('\n')
247 except Exception, e:
248 print >> sys.stderr, "failed: %s" % e
249 exit(1)
250
251
252 if __name__ == "__main__" : __main__()
253