--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/snpeff_to_peptides.py	Fri Feb 07 15:05:20 2014 -0500
@@ -0,0 +1,239 @@
+#!/usr/bin/env python
+"""
+#
+#------------------------------------------------------------------------------
+#                         University of Minnesota
+#         Copyright 2013, Regents of the University of Minnesota
+#------------------------------------------------------------------------------
+# Author:
+#
+#  James E Johnson
+#
+#------------------------------------------------------------------------------
+"""
+
+
+"""
+This tool takes a SnpEff VCF file and an Ensembl pep.all.fa file ( e.g. Homo_sapiens.GRCh37.73.pep.all.fa )
+It outputs a peptide fasta file with the variant peptide sequence that result from NON_SYNONYMOUS_CODING effects 
+
+"""
+
+import sys,re,os.path
+import tempfile
+import optparse
+from optparse import OptionParser
+import logging
+
+## dictionary for Amino Acid Abbreviations
+aa_abbrev_dict = dict()
+aa_abbrev_dict['Phe'] = 'F'
+aa_abbrev_dict['Leu'] = 'L'
+aa_abbrev_dict['Ser'] = 'S'
+aa_abbrev_dict['Tyr'] = 'Y'
+aa_abbrev_dict['Cys'] = 'C'
+aa_abbrev_dict['Trp'] = 'W'
+aa_abbrev_dict['Pro'] = 'P'
+aa_abbrev_dict['His'] = 'H'
+aa_abbrev_dict['Gln'] = 'Q'
+aa_abbrev_dict['Arg'] = 'R'
+aa_abbrev_dict['Ile'] = 'I'
+aa_abbrev_dict['Met'] = 'M'
+aa_abbrev_dict['Thr'] = 'T'
+aa_abbrev_dict['Asn'] = 'N'
+aa_abbrev_dict['Lys'] = 'K'
+aa_abbrev_dict['Val'] = 'V'
+aa_abbrev_dict['Ala'] = 'A'
+aa_abbrev_dict['Asp'] = 'D'
+aa_abbrev_dict['Glu'] = 'E'
+aa_abbrev_dict['Gly'] = 'G'
+
+##  Get the peptide ID and sequence a given ID 
+def get_sequence(id,seq_file):
+  fh = open(seq_file, 'r')
+  try:
+    for (ln,line) in enumerate(fh):
+      if line.find(id) >= 0:
+        fields = line.split('\t')
+        return ( ' '.join(fields[0:-1]),fields[-1].rstrip() if fields and len(fields) > 0 else None )
+  except Exception, e:
+    print >> sys.stderr, "failed: %s" % e
+  finally:
+    fh.close()
+
+def fasta_to_tabular(fasta_file,tabular_file):
+  inFile = open(fasta_file,'r')
+  outFile = open(tabular_file,'w') 
+  for i, line in enumerate( inFile ):
+    line = line.rstrip( '\r\n' )
+    if not line or line.startswith( '#' ):
+      continue
+    if line.startswith( '>' ):
+      #Don't want any existing tabs to trigger extra columns:
+      line = line.replace('\t', ' ')
+      if i > 0:
+        outFile.write('\n')
+      outFile.write(line[1:])
+      outFile.write('\t')
+    else:
+      outFile.write(line)
+  if i > 0:
+    outFile.write('\n')
+  if inFile:
+    inFile.close()
+  if outFile:
+    outFile.close()
+
+def __main__():
+  #Parse Command Line
+  parser = optparse.OptionParser()
+  parser.add_option( '-i', '--input', dest='input', help='The input snpeff vcf file with HGVS annotations (else read from stdin)' )
+  parser.add_option( '-o', '--output', dest='output', help='The output fasta (else write to stdout)' )
+  parser.add_option( '-p', '--protein_fasta', dest='protein_fasta', default=None, help='The Esembl protein fasta in tabular format' )
+  parser.add_option( '-l', '--leading_aa_num', dest='leading_aa_num', type='int', default=None, help='leading number of AAs to output' )
+  parser.add_option( '-t', '--trailing_aa_num', dest='trailing_aa_num', type='int', default=None, help='trailing number of AAs to output' )
+  parser.add_option( '-d', '--debug', dest='debug', action='store_true', default=False, help='Turn on wrapper debugging to stdout'  )
+  (options, args) = parser.parse_args()
+
+  # need protein_fasta file
+  fastaFile = options.protein_fasta
+  if options.protein_fasta == None:
+    print >> sys.stderr, "Ensembl protein_fasta tabular file required"
+    exit(4)
+  else:
+    # determine if fasta is already in tabular format
+    is_tabular = False
+    standard_aa = '^[AC-IK-WY]+$'
+    standard_na = '^[ACGTN]+$'
+    inFile = open(fastaFile,'r')
+    try:
+      nseq = 0
+      for i, line in enumerate( inFile ):
+        line = line.rstrip( '\r\n' )
+        if not line or line.startswith( '#' ):
+          continue
+        fields = line.split('\t')
+        if len(fields) < 2: 
+          is_tabular = False
+          if line[0] != '>':
+            print >> sys.stderr, "failed: %s does not appear to be a fasta file" % fastaFile
+            exit(4)
+          break
+        if re.match('^[A-Z]+$',fields[-1].upper()): 
+          is_tabular = True
+          nseq += 1
+        else:
+          if line[0] != '>':
+            print >> sys.stderr, "failed: %s does not appear to be a fasta file" % fastaFile
+            exit(4)
+        if nseq > 10:
+          break
+    finally:
+      if inFile:
+        inFile.close()
+    if not is_tabular:
+      fastaFile = tempfile.NamedTemporaryFile(prefix='pep_fasta_',suffix=".tab",dir=os.getcwd()).name
+      fasta_to_tabular(options.protein_fasta,fastaFile)
+  # vcf input 
+  if options.input != None:
+    try:
+      inputPath = os.path.abspath(options.input)
+      inputFile = open(inputPath, 'r')
+    except Exception, e:
+      print >> sys.stderr, "failed: %s" % e
+      exit(2)
+  else:
+    inputFile = sys.stdin
+  # output 
+  if options.output != None:
+    try:
+      outputPath = os.path.abspath(options.output)
+      outputFile = open(outputPath, 'w')
+    except Exception, e:
+      print >> sys.stderr, "failed: %s" % e
+      exit(3)
+  else:
+    outputFile = sys.stdout
+  ## Amino_Acid_Change notations
+  # G528R
+  # p.Gly528Arg/c.1582G>C
+  aa_change_regex = '([A-Z])(\d+)([A-Z])' # G528R
+  aa_hgvs_regex = 'p\.([A-Z][a-z][a-z])(\d+)([A-Z][a-z][a-z])(/c\.(\d+)([ACGTN])>([ACGTN]))' # p.Gly528Arg/c.1582G>C
+  # Save VCF file header, not currently used
+  vcf_header = [] 
+  reading_entries = False
+  try:
+    for linenum,line in enumerate(inputFile):
+      ## print >> sys.stderr, "%d: %s\n" % (linenum,line)
+      if line.startswith('##'):
+        vcf_header.append(line)
+        # May need to check SnpEff version in the header, the EFF info changed between versions 2 and 3
+        ##SnpEffVersion
+      elif line.startswith('#CHROM'):
+        reading_entries = True
+      else:
+        fields = line.split('\t')
+        # This is the current format of the EFF entry:
+        # EFF=missense(MODERATE|MISSENSE|Ggg/Cgg|G528R|802|SCNN1D|protein_coding|CODING|ENST00000379116|12|1);OICR=(ENST00000379116|1808) 
+        # If this becomes variable, will need to dynamically pattern this on the defintion in the vcf header:
+        ##INFO=<ID=EFF,Number=.,Type=String,Description="Predicted effects for this variant.Format: 'Effect ( Effect_Impact | Functional_Class | Codon_Change | Amino_Acid_Change| Amino_Acid_length | Gene_Name | Transcript_BioType | Gene_Coding | Transcript_ID | Exon_Rank | Genotype_Number [ | ERRORS | WARNINGS ] )' ">
+        (chrom,pos,id,ref,alts,qual,filter,info) = fields[0:8]
+        for info_item in info.split(';'):
+          try:
+            if info_item.find('=') < 0:
+              continue
+            (key,val) = info_item.split('=',1)
+            if key == 'EFF':
+              effects = val.split(',')
+              for effect in effects:
+                (eff,effs) = effect.rstrip(')').split('(')
+                if not eff == 'NON_SYNONYMOUS_CODING':
+                  continue
+                eff_fields = effs.split('|')
+                (impact,functional_class,codon_change,aa_change,aa_len,gene_name,biotype,coding,transcript,exon) = eff_fields[0:10]
+                if transcript:
+                  aa_pos = None # 1-based position
+                  alt_aa = '_' 
+                  # parse aa_change
+                  # get AA change position and alternate Animo Acid
+                  sap = aa_change
+                  m = re.match(aa_change_regex,aa_change)
+                  if m:
+                    aa_pos = int(m.groups()[1])
+                    alt_aa = m.groups()[2]
+                  else:
+                    m = re.match(aa_hgvs_regex,aa_change)
+                    if m:
+                      aa_pos = int(m.groups()[1])
+                      ref_aa = aa_abbrev_dict[m.groups()[0]]
+                      alt_aa = aa_abbrev_dict[m.groups()[2]]
+                      sap = "%s%d%s" % (ref_aa,aa_pos,alt_aa)
+                  if not aa_pos:
+                    continue
+                  # get AA sequence
+                  aa_offset = aa_pos - 1
+                  (pep_id,pep_seq) = get_sequence(transcript,fastaFile)
+                  if not pep_seq:
+                    continue
+                  start_pos = max(aa_offset - options.leading_aa_num, 0) if options.leading_aa_num else 0
+                  end_pos = min(aa_offset + options.trailing_aa_num + 1, len(pep_seq)) if options.trailing_aa_num else len(pep_seq)
+                  # transform sequence
+                  alt_seq = pep_seq[start_pos:aa_offset] + alt_aa + pep_seq[aa_offset+1:end_pos]
+                  # >ENSP00000363782 pep:known chromosome:GRCh37:1:22778472:22853855:1 gene:ENSG00000184677 transcript:ENST00000374651 gene_biotype:protein_coding transcript_biotype:protein_coding snp_location:1:22778472 codon_change:Gtg/Atg sap:V885M
+                  pep_id = re.sub('pep:[a-z]*','pep:sap',pep_id)
+                  hdr = ">%s snp_location:%s:%s codon_change:%s sap:%s\n" % (pep_id, chrom, pos, codon_change, sap)
+                  outputFile.write(hdr)
+                  if options.debug:
+                    trimmed_seq = pep_seq[start_pos:end_pos]
+                    outputFile.write(trimmed_seq)
+                    outputFile.write('\n')
+                  outputFile.write(alt_seq)
+                  outputFile.write('\n')
+          except Exception, e:
+            print >> sys.stderr, "failed: %s" % e
+  except Exception, e:
+    print >> sys.stderr, "failed: %s" % e
+    exit(1)
+
+if __name__ == "__main__" : __main__()
+