89422546b1bfadf27a115ae774571a5f57a916d8 chmalee Tue Jan 18 14:37:33 2022 -0800 Re-do the v2.1.1 (hg19) and v3.1.1 (hg38) versions of the gnomad tracks after a user found we were incorrectly pre-filtering intergenic variants from the whole genome data sets, refs #28666 diff --git src/hg/makeDb/gnomad/gnomadVcfBedToBigBed src/hg/makeDb/gnomad/gnomadVcfBedToBigBed index 21b8544..30026e5 100755 --- src/hg/makeDb/gnomad/gnomadVcfBedToBigBed +++ src/hg/makeDb/gnomad/gnomadVcfBedToBigBed @@ -1,542 +1,552 @@ #!/cluster/software/bin/python3 """ Helper script to do some gnomAD specific stuff to the vcfToBed output NOTE: This script is dependent on the format of the VEP INFO field in a particular VCF file. Use the -v option to pass the right version options to this script, and if necessary, add a new one. Example format for the v2.1.1 version of gnomAD: ##INFO=<ID=vep,Number=.,Type=String,Description="Consequence annotations from Ensembl VEP. \ Format: \ Allele|Consequence|IMPACT|SYMBOL|Gene|Feature_type|Feature|BIOTYPE|EXON|INTRON|HGVSc\ |HGVSp|cDNA _position|CDS_position|Protein_position|Amino_acids|Codons\ |Existing_variation|ALLELE_NUM|DISTANCE|STRAND|FLAGS|VARIANT_CLASS|MINIMISED\ |SYMBOL_SOURCE|HGNC_ID|CANONICAL|TSL|APPRIS|CCDS|ENSP|SWISSPROT|TREMBL|UNIPARC\ |GENE_PHENO|SIFT|PolyPhen|DOMAINS|HGVS_OFFSET|GMAF|AFR_MAF|AMR_MAF|EAS_MAF|EUR_MAF\ |SAS_MAF|AA_MAF|EA_MAF|ExAC_MAF|ExAC_Adj_MAF|ExAC_AFR_MAF|ExAC_AMR_MAF|ExAC_EAS_MAF\ |ExAC_FIN_MAF|ExAC_NFE_MAF|ExAC_OTH_MAF|ExAC_SAS_MAF|CLIN_SIG|SOMATIC|PHENO|PUBMED\ |MOTIF_NAME|MOTIF_POS|HIGH_INF_POS|MOTIF_SCORE_CHANGE|LoF|LoF_filter|LoF_flags|LoF_info"> """ import sys, argparse, hashlib,json from collections import defaultdict,namedtuple,OrderedDict # which version of gnomAD for parsing VEP string versions = ["v2.1.1", "v3.1", "v3.1_chrM", "v3.1.1"] # the number of fields in the VEP string (depends on version): # how to count: # bcftools view -h in.vcf.gz | grep "^##INFO=<ID=vep" | grep -o "Format:.*" \ # | tr '|' '\t' | tl0 | wc -l numVepFields = {"v2.1.1" : 68, "v3.1": 45, "v3.1_chrM": 45, "v3.1.1": 45} # the different pipe separated fields in the VEP struct # how to get: # bcftools view -h in.vcf.gz | grep "^##INFO=<ID=vep" | grep -o "Format: .*" \ # | cut -d' ' -f2- | cut -d'"' -f1 | sed -e 's/^/"/' -e 's/$/"/' -e 's/|/", "/g' versionVepFields = { "v3.1.1": [ "Allele", "Consequence", "IMPACT", "SYMBOL", "Gene", "Feature_type", "Feature", "BIOTYPE", "EXON", "INTRON", "HGVSc", "HGVSp", "cDNA_position", "CDS_position", "Protein_position", "Amino_acids", "Codons", "ALLELE_NUM", "DISTANCE", "STRAND", "VARIANT_CLASS", "MINIMISED", "SYMBOL_SOURCE", "HGNC_ID", "CANONICAL", "TSL", "APPRIS", "CCDS", "ENSP", "SWISSPROT", "TREMBL", "UNIPARC", "GENE_PHENO", "SIFT", "PolyPhen", "DOMAINS", "HGVS_OFFSET", "MOTIF_NAME", "MOTIF_POS", "HIGH_INF_POS", "MOTIF_SCORE_CHANGE", "LoF", "LoF_filter", "LoF_flags", "LoF_info" ], "v3.1_chrM": [ "Allele", "Consequence", "IMPACT", "SYMBOL", "Gene", "Feature_type", "Feature", "BIOTYPE", "EXON", "INTRON", "HGVSc", "HGVSp", "cDNA_position", "CDS_position", "Protein_position", "Amino_acids", "Codons", "ALLELE_NUM", "DISTANCE", "STRAND", "VARIANT_CLASS", "MINIMISED", "SYMBOL_SOURCE", "HGNC_ID", "CANONICAL", "TSL", "APPRIS", "CCDS", "ENSP", "SWISSPROT", "TREMBL", "UNIPARC", "GENE_PHENO", "SIFT", "PolyPhen", "DOMAINS", "HGVS_OFFSET", "MOTIF_NAME", "MOTIF_POS", "HIGH_INF_POS", "MOTIF_SCORE_CHANGE", "LoF", "LoF_filter", "LoF_flags", "LoF_info" ], "v3.1": [ "Allele", "Consequence", "IMPACT", "SYMBOL", "Gene", "Feature_type", "Feature", "BIOTYPE", "EXON", "INTRON", "HGVSc", "HGVSp", "cDNA_position", "CDS_position", "Protein_position", "Amino_acids", "Codons", "ALLELE_NUM", "DISTANCE", "STRAND", "VARIANT_CLASS", "MINIMISED", "SYMBOL_SOURCE", "HGNC_ID", "CANONICAL", "TSL", "APPRIS", "CCDS", "ENSP", "SWISSPROT", "TREMBL", "UNIPARC", "GENE_PHENO", "SIFT", "PolyPhen", "DOMAINS", "HGVS_OFFSET", "MOTIF_NAME", "MOTIF_POS", "HIGH_INF_POS", "MOTIF_SCORE_CHANGE", "LoF", "LoF_filter", "LoF_flags", "LoF_info" ], "v2.1.1": [ "Allele", "Consequence", "IMPACT", "SYMBOL", "Gene", "Feature_type", "Feature", "BIOTYPE", "EXON", "INTRON", "HGVSc", "HGVSp", "cDNA_position", "CDS_position", "Protein_position", "Amino_acids", "Codons", "Existing_variation", "ALLELE_NUM", "DISTANCE", "STRAND", "FLAGS", "VARIANT_CLASS", "MINIMISED", "SYMBOL_SOURCE", "HGNC_ID", "CANONICAL", "TSL", "APPRIS", "CCDS", "ENSP", "SWISSPROT", "TREMBL", "UNIPARC", "GENE_PHENO", "SIFT", "PolyPhen", "DOMAINS", "HGVS_OFFSET", "GMAF", "AFR_MAF", "AMR_MAF", "EAS_MAF", "EUR_MAF", "SAS_MAF", "AA_MAF", "EA_MAF", "ExAC_MAF", "ExAC_Adj_MAF", "ExAC_AFR_MAF", "ExAC_AMR_MAF", "ExAC_EAS_MAF", "ExAC_FIN_MAF", "ExAC_NFE_MAF", "ExAC_OTH_MAF", "ExAC_SAS_MAF", "CLIN_SIG", "SOMATIC", "PHENO", "PUBMED", "MOTIF_NAME", "MOTIF_POS", "HIGH_INF_POS", "MOTIF_SCORE_CHANGE", "LoF", "LoF_filter", "LoF_flags", "LoF_info" ] } versionPops = { "v3.1.1": ["afr", "ami", "amr", "asj", "eas", "fin", "mid", "nfe", "sas", "oth", "XX", "XY"], "v3.1_chrM": ['afr', 'ami', 'amr', 'asj', 'eas', 'fin', 'nfe', 'oth', 'sas', 'mid'], "v3.1": ["afr", "amr", "asj", "eas", "fin", "mid", "ami", "nfe", "sas", "oth", "XX", "XY"], "v2.1.1":["afr", "amr", "asj", "eas", "fin", "nfe", "sas", "oth"] } chrM_haplo_groups = [ 'A', 'B', 'C', 'D', 'E', 'F', 'G', 'H', 'HV', 'I', 'J', 'K', 'L0', 'L1', 'L2', 'L3', 'L4', 'L5', 'M', 'N', 'P', 'R', 'T', 'U', 'V', 'W', 'X', 'Y', 'Z' ] # the fields that MUST be in the bigBed (for filters, etc) versionAutoSql = { "v3.1.1": ["chrom", "chromStart", "chromEnd", "name", "score", "strand", "thickStart", "thickEnd", "itemRgb", "ref", "alt", "FILTER", "AC", "AN", "AF", "faf95", "nhomalt", "rsId", "genes", "annot", "variation_type", "_startPos", "displayName"], "v3.1_chrM": ["chrom", "chromStart", "chromEnd", "name", "score", "strand", "thickStart", "thickEnd", "itemRgb", "ref", "alt", "FILTER", "AC", "AN", "AF", "faf95", "nhomalt", "rsId", "genes", "annot", "variation_type", "_startPos", "displayName"], "v3.1": ["chrom", "chromStart", "chromEnd", "name", "score", "strand", "thickStart", "thickEnd", "itemRgb", "ref", "alt", "FILTER", "AC", "AN", "AF", "faf95", "nhomalt", "rsId", "genes", "annot", "variation_type", "_startPos", "displayName"], "v2.1.1": ["chrom", "chromStart", "chromEnd", "name", "score", "strand", "thickStart", "thickEnd", "itemRgb", "ref", "alt", "FILTER", "AC", "AN", "AF", "faf95", "nhomalt", "rsId", "genes", "annot", "variation_type", - "pLoF", "lofFlags", "lofCuration", "pLoFCurationFlags", "_startPos", "displayName"] + "_startPos", "displayName", "pLoF", "lofFlags", "lofCuration", "pLoFCurationFlags"] } # the fields in the extra tab file, specify order here so we have the same order # across different runs for different chromosomes versionExtraFields = { "v3.1.1": ["_key", "_jsonVep", "_jsonPopTable", "cadd_phred", "revel_score", "splice_ai_max_ds", "splice_ai_consequence", "primate_ai_score"], "v3.1_chrM": ["_key", "_jsonVep", "_jsonPopTable", "_jsonHapTable"], "v3.1": ["hgvsc", "hgvsp", "popmax", *[x + "_" + y for y in ["popmax", "afr", "ami", "amr", "asj", "eas", "fin", "mid", "nfe", "sas", "oth", "XX", "XY"] for x in ["AC", "AN", "AF", "nhomalt"]], "cadd_phred", "revel_score", "splice_ai_max_ds", "splice_ai_consequence", "primate_ai_score"], - "v2.1.1": ["hgvsc", "hgvsp", "popmax", *[x + "_" + y for y in ["popmax", "afr", "amr", - "asj", "eas", "fin", "nfe", "oth", "female", "male"] for x in ["AC", "AN", "AF", - "nhomalt"]]] + "v2.1.1": ["hgvsc", "hgvsp", "popmax", "AC_popmax", "AN_popmax", "AF_popmax", + *[x + "_" + y for y in ["afr", "amr", "asj", "eas", "fin", "nfe", "oth", + "female", "male"] for x in ["AC", "AN", "AF", "nhomalt"]]] } # determines the color of the variant in the browser plofTypes = ["frameshift", "stop gained", "splice donor", "splice acceptor"] missenseTypes = ["missense", "inframe deletion", "inframe insertion", "start lost", "stop list"] synTypes = ["synonymous"] # for printing the name of the popmax: popAbbr = {"afr": "African/African American", "amr": "Latino/Admixed American", "asj": "Ashkenazi Jewish", "eas": "East Asian", "fin": "Finnish", "mid": "Middle Eastern", "ami": "Amish", "nfe": "Non-Finnish European", "sas": "South Asian", "oth": "Other (population not assigned)"} lofDesc = {"HC": "High-confidence", "OS": "Other Splice (beta)", "LC": "Low-confidence"} header = None def parseCommandLine(): parser = argparse.ArgumentParser(formatter_class=argparse.RawDescriptionHelpFormatter, description="""Transform gnomAD VCF to bigBed. This looks something like: vcfToBed -fields="list,of,info,fields" in.vcf.gz firstOut.bed gnomadVcfBedToBigBed -v v2.1.1 -lof lofFile.txt firstOut.bed finalOut.bed""", ) parser.add_argument("infile", help="Input bed file with a vep field, use 'stdin' to read \ from stdin") parser.add_argument("-lof", "--lofFilePath", action="store", help="Path to tab separated \ loss-of-function curation file, where the first line is a header describing each \ of the fields") parser.add_argument("-v", "--version", action="store", help="Version of gnomAD. Each \ version of gnomAD tends to have slightly different VEP annotations or populations, \ so you can specify what you are working with here. Current supported versions: %s" % ", ".join(versions)) parser.add_argument("-e", "--extra-output-file", action="store", help="Output fields not necessary for display to this extra file instead") parser.add_argument("outfile", help="Output bed file name, use 'stdout' to write to stdout") args = parser.parse_args() if not args.version or args.version not in versions: sys.stderr.write("ERROR: missing version or wrong version. Please supply -v VERSION where VERSION is one of: [%s]\n" % ", ".join(versions)) sys.exit(255) if args.extra_output_file and args.extra_output_file == "stdout" and args.extra_output_file == args.infile: sys.stderr.write("ERROR: Only one of infile and --extra-output-file can be stdout.") sys.exit(255) return args def writeHeaders(version, outfh, extrafh): """Write out the field names""" outfh.write("#" + "\t".join(x for x in versionAutoSql[version])) if extrafh: if version == "v3.1.1" or version == "v3.1_chrM": extrafh.write("#" + "\t".join(versionExtraFields["v3.1.1"] + ["_jsonHapTable"])) else: extrafh.write("#" + "\t".join(versionExtraFields[version])) extrafh.write("\n") else: - outfh.write("\t" + "#" + "\t".join(versionExtraFields[version])) + outfh.write("\t" + "\t".join(versionExtraFields[version])) outfh.write("\n") def parseHeader(headerStr, infh, outfh, extraFh): """Parse the field names out of a header string""" global header headerStr = headerStr[1:] # chop off '#' fields = headerStr.strip('\n').split('\t') if not header: header = fields outfh.write("#%s\n" % ("\t".join(header[:17] + ["rsID","genes","annot","variation_type","_startPos"] + ["hgvsc", "hgvsp"]+ header[18:]))) elif fields != header: sys.stderr.write("Header differs from others: '%s'\n" % infh.name) sys.exit(1) def pickColor(consequenceList): """Assign a color to this item based on it's predicted consequences""" cleanedList = [x.replace("variant","").lower().replace("_", " ").strip() for x in consequenceList] if any(item in plofTypes for item in cleanedList): return "pLoF", "255,32,0" elif any(item in missenseTypes for item in cleanedList): return "missense", "247,189,0" elif any(item in synTypes for item in cleanedList): return "synonymous", "4,255,0" else: return "other", "95,95,95" def unshiftLeftPad(start, ref, alt): """When an indel has been left-padded in VCF, vcfToBed will shift the start position by one, which is correct for browser display, but is wrong for link-outs. Because VCF also uses 1-based coordinates, the correct link out will be the 0-based start for a shifted variant, and the 1-based start for everything else.""" if (ref != "-" and ref != alt and ref[0] == alt[0]): return start else: return start + 1 def flagsForVar(lofDict, x): """Returns the relevant flags for why a variant is loss-of-function or not""" flags = "" if x in lofDict: flags = ", ".join([flag.replace("Flag ", "") for flag in lofDict[x] if lofDict[x][flag] == "TRUE"]) return flags def getLofCurationKey(version, ucscChrom, unshiftedStart, ref, alt): """Form the key into lofDict for a given variant""" if version == "v2.1.1": chrom = ucscChrom.replace("chr","") return "-".join([chrom, unshiftedStart, ref, alt]) lofCurationStrs = { "likely_lof": "Curated as Likely LoF", "likely_not_lof": "Curated as Likely Not LoF", "lof": "Curated as LoF", "not_lof": "Curated as Not LoF", "uncertain": "Curated as Uncertain" } def getLofCuration(lofDict, version, ucscChrom, unshiftedStart, ref, alt): """Return the lof curation info for a variant, or an empty list""" key = getLofCurationKey(version, ucscChrom, unshiftedStart, ref, alt) curation = "" flags = "" if key in lofDict: curation = lofDict[key]["Verdict"] if curation != "lof": flags = flagsForVar(lofDict, key) curation = lofCurationStrs[curation] return [curation, flags] def buildMitoStructs(versionPopNames, extraFieldList): """Turn the chrM specific fields into the data structures we want to show""" hapDict = OrderedDict() popDict = OrderedDict() i = 0 hapDict["Haplogroup"] = ["Allele Number", "Homoplasmic AC", "Homoplasmic AF", "Heteroplasmic AC", "Heteroplasmic AF"] hap_an = extraFieldList[0].split("|") hap_ac_het = extraFieldList[1].split("|") hap_ac_hom = extraFieldList[2].split("|") hap_af_hom = extraFieldList[3].split("|") hap_af_het = extraFieldList[4].split("|") for ix, hapName in enumerate(chrM_haplo_groups): hapDict[hapName] = [hap_an[ix], hap_ac_hom[ix], hap_af_hom[ix], hap_ac_het[ix], hap_af_het[ix]] hap_an = sum([int(x) for x in hap_an]) total_hap_ac_hom = sum([int(x) for x in hap_ac_hom]) total_hap_ac_het = sum([int(x) for x in hap_ac_het]) hapDict["Total"] = [hap_an, total_hap_ac_hom, total_hap_ac_hom/hap_an, total_hap_ac_het, total_hap_ac_het/hap_an] pop_an = extraFieldList[9].split("|") pop_ac_het = extraFieldList[10].split("|") pop_ac_hom = extraFieldList[11].split("|") pop_af_hom = extraFieldList[12].split("|") pop_af_het = extraFieldList[13].split("|") popDict["Populations"] = ["Allele Number", "Homoplasmic AC", "Homoplasmic AF", "Heteroplasmic AC", "Heteroplasmic AF"] for ix, popName in enumerate(versionPopNames): popDict[popName] = [pop_an[ix], pop_ac_hom[ix], pop_af_hom[ix], pop_ac_het[ix], pop_af_het[ix]] hom_af, het_af = extraFieldList[16].split("/") hom_ac, het_ac = extraFieldList[14].split("/") popDict["Total"] = [extraFieldList[15], hom_ac, hom_af, het_ac, het_af] other = hapDict return popDict, other def convertExtraFields(extraFieldList, version): """Split the population data from the other extra fields and return the population data as a json blob and the other fields as a list""" versionPopNames = [] for x in versionPops[version]: if x in popAbbr: versionPopNames.append(popAbbr[x]) else: versionPopNames.append(x) if version == "v3.1.1": versionPopNames.append("Total") popData = extraFieldList[4:-9] + extraFieldList[-4:] popDict = OrderedDict() # for keeping the header line first and total line last # in the final bigBed popDict["Populations"] = ["Allele Count", "Allele Number", "Allele Frequency", "Number of Homozygotes"] i = 0 for popName in versionPopNames: val = popData[i:i+4] key = popAbbr[popName] if popName in popAbbr else popName popDict[key] = val i += 4 # Add an extra field for the chrM only haplogroup table other = extraFieldList[-9:-4] + [""] else: popDict, other = buildMitoStructs(versionPopNames, extraFieldList) return popDict,other def splitVepField(vep, version): """Split the VEP string into a list of strings for each annotation. Because commas both delimit the multiple annotations of a single variant, and can be part of the pipe separated strings that make up a single annotation, we can't just split on ',' like normal""" ret = [] # at the versionSpecific index '|', go back until we find a comma or | and split there ix = 1 copy = vep.split('|') try: numFields = numVepFields[version] except ValueError: sys.stderr.write("ERROR: version '%s' not a supported version. Currently \ supported versions: [%s]\n" % ", ".join(versions)) sys.exit(255) for i in range(round(len(copy) / numFields)): start = 0 # I think there is a bug in the version of VEP used to annotate chrM where # the comma separating annotations is stripped, leaving the indexing off by one if version == "v3.1_chrM": start = i*numFields else: start = (i*numFields) - (i*1) end = numFields + (numFields*i) - i #print("start = %d, end = %d" % (start,end)) thisElem = copy[start:end] if thisElem: # fix up the first element which may contain part of the previous annotation #print("1. thisElem[0]: %s, thisElem[-1]: %s" % (thisElem[0], thisElem[-1])) if i != 0 and ',' in thisElem[0]: thisElem[0] = thisElem[0].split(',')[-1] #print("2. thisElem[0]: %s, thisElem[-1]: %s" % (thisElem[0], thisElem[-1])) # NON-chrM: the last element will always contain part of the next annotation # if the last elem was empty then it is just the start of the next annotation if thisElem[-1]: thisElem[-1] = ",".join(thisElem[-1].split(',')[:-1]) #print("3. thisElem[0]: %s, thisElem[-1]: %s" % (thisElem[0], thisElem[-1])) #assert(len(thisElem) == numFields) ret.append("|".join(thisElem)) return ret def parseVep(vep, version): """Return a more compacted version of the VEP annotations for a variant, organized by the affected genes""" genes = defaultdict(dict) annotList = splitVepField(vep, version) for annot in annotList: group = annot.split('|') if "&" in group[1]: consList = group[1].split('&') else: consList = [group[1]] - if "regulatory_region_variant" in consList \ - or "downstream_gene_variant" in consList \ - or "upstream_gene_variant" in consList \ - or "TF_binding_site_variant" in consList \ - or "intergenic_variant" in consList: - continue + #if "regulatory_region_variant" in consList \ + # or "downstream_gene_variant" in consList \ + # or "upstream_gene_variant" in consList \ + # or "TF_binding_site_variant" in consList \ + # or "intergenic_variant" in consList: + # continue vepFields = dict(zip(versionVepFields[version],group)) - gene = vepFields["SYMBOL"] + gene = vepFields["SYMBOL"] if vepFields["SYMBOL"] != "" else "N/A" hgvsc = [vepFields["HGVSc"]] if vepFields["HGVSc"] != "" else None hgvsp = [vepFields["HGVSp"]] if vepFields["HGVSp"] != "" else None lof = [vepFields["LoF"]] if vepFields["LoF"] != "" else None lofFlags = [vepFields["LoF_flags"]] if vepFields["LoF_flags"] != "" else None lofFilter = [vepFields["LoF_filter"]] if vepFields["LoF_filter"] != "" else None if lof: try: for i,x in enumerate(lof): if x == "LC": lof[i] = "Low Confidence (%s)" % lofFilter[i] else: lof[i] = lofDesc[x] except KeyError: sys.stderr.write("ERROR parsing lof information:\n") sys.stderr.write("lof: %s\n" % lof) sys.stderr.write("lofFlags: %s\n" % lof) sys.stderr.write("lofFilter: %s\n" % lof) sys.exit(255) if gene in genes: genes[gene]["cons"].update(list(consList)) if hgvsc: genes[gene]["hgvsc"].update(hgvsc) if hgvsp: genes[gene]["hgvsp"].update(hgvsp) if lof: genes[gene]["pLoF"] = set(lof) if lofFlags: genes[gene]["Flag"] = set(lofFlags) else: genes[gene]["cons"] = set(consList) genes[gene]["hgvsc"] = set(hgvsc) if hgvsc else set() genes[gene]["hgvsp"] = set(hgvsp) if hgvsp else set() genes[gene]["pLoF"] = set(lof) if lof else set() genes[gene]["Flag"] = set(lof) if lofFlags else set() for gene in genes: genes[gene]["cons"] = list(genes[gene]["cons"]) genes[gene]["hgvsc"] = list(genes[gene]["hgvsc"]) genes[gene]["hgvsp"] = list(genes[gene]["hgvsp"]) genes[gene]["pLoF"] = list(genes[gene]["pLoF"]) genes[gene]["Flag"] = list(genes[gene]["Flag"]) return genes def gnomadVcfBedToBigBed(infh, outfh, extraFh, version, lofDict): """Read from already opened infh, convert to more compact bed format, then write to already opened outfh, optionally use extraFh for non-necessary bed fields.""" writeHeaders(version, outfh, extraFh) for line in infh: genes = defaultdict(dict) extraInfo = [] if line.startswith("#"): continue #parseHeader(line, infh, outfh, extraFh) #continue fixedLine = line.strip('\n').split('\t') chrom, chromStart, chromEnd, bedName, score, strand, thickStart, thickEnd = fixedLine[:8] color = fixedLine[8] # defaults to black ref, alt, filterTag = fixedLine[9:12] filterTag = filterTag.replace(";",",") # replace so trackDb filterValues works if "chrM" not in version: vep = fixedLine[17] ac, an, af, faf95, nhomalt = fixedLine[12:17] maybeExtraFields = [x if x else "N/A" for x in fixedLine[18:]] else: vep = fixedLine[12] # ac and af are really AC_hom/AC_het and AF_hom/AF_het ac = fixedLine[14] + "/" + fixedLine[15] af = fixedLine[18] + "/" + fixedLine[19] an = fixedLine[13] faf95 = "" nhomalt = "" maybeExtraFields = fixedLine[16:18] + fixedLine[20:] if vep != "": genes = parseVep(vep, version) # Now that we've parsed all the incoming fields from vcfToBed, write # output to final bed, and maybe to extra tab file: - if genes: + #if genes: consList = [] for gene in genes: consList += list(genes[gene]["cons"]) annot,color = pickColor(consList) rsId = "" if bedName.startswith("rs"): rsId = bedName unshiftedStart = unshiftLeftPad(int(chromStart), ref, alt) displayName = chrom + "-" + str(unshiftedStart) + "-" displayName += ref[:10]+"..." if len(ref) > 13 else ref displayName += "-" displayName += alt[:10]+"..." if len(alt) > 13 else alt name = hashlib.md5(str.encode(chrom+chromStart+chromEnd+ref+alt)).hexdigest() if version == "v3.1.1" or version == "v3.1_chrM": outfh.write("\t".join([chrom, chromStart, chromEnd, name, score, strand, thickStart, thickEnd, color, ref, alt, filterTag, ac, an, af, faf95, nhomalt, rsId, ", ".join(genes.keys()), annot, ",".join(consList), str(unshiftedStart), displayName])) popTable, otherFields = convertExtraFields(maybeExtraFields + [ac, an, af, nhomalt], version) if version == "v3.1_chrM": # otherFields is the haplotype table plus empties for the v3.1.1 fields: otherFields = ["" for i in range(5)] + [json.dumps(otherFields)] if extraFh: extraFh.write("\t".join([name, json.dumps(genes), json.dumps(popTable)] + otherFields)) extraFh.write("\n") else: outfh.write("\t" + "\t".join([name] + [json.dumps(genes), json.dumps(popTable)] + otherFields)) outfh.write("\n") elif version == "v3.1": hgvscList = [", ".join(list(genes[gene]["hgvsc"]))] hgvspList = [", ".join(list(genes[gene]["hgvsp"]))] pLoFList = [", ".join(list(genes[gene]["pLoF"]))] pLoFFlags = [", ".join(list(genes[gene]["Flag"]))] outfh.write("\t".join([chrom, chromStart, chromEnd, name, score, strand, thickStart, thickEnd, color, ref, alt, filterTag, ac, an, af, faf95, nhomalt, rsId, gene, annot, *consList, str(unshiftedStart), displayName])) if extraFh: extraFh.write("\t".join([name] + hgvscList + hgvspList + maybeExtraFields)) extraFh.write("\n") else: outfh.write("\t" + "\t".join([name] + hgvscList + hgvspList + maybeExtraFields)) outfh.write("\n") else: - pLoFCuration = getLofCuration(lofDict, version, bed8Fields[0], + pLoFCuration = getLofCuration(lofDict, version, chrom, str(unshiftedStart), ref, alt) + hgvscList = [x for x in genes[gene]["hgvsc"] for gene in genes] + hgvspList = [x for x in genes[gene]["hgvsp"] for gene in genes] + pLoFList = [x for x in genes[gene]["pLoF"] for gene in genes] + pLoFFlags = [x for x in genes[gene]["Flag"] for gene in genes] outfh.write("\t".join([chrom, chromStart, chromEnd, name, score, strand, thickStart, thickEnd, color, ref, alt, filterTag, ac, an, af, faf95, nhomalt, - rsId, gene, annot, *consList, displayName])) - outfh.write("\t" + "\t".join(pLoFCuration, [str(unshiftedStart)])) + rsId, ", ".join(genes.keys()), annot, ", ".join(consList)])) + outfh.write("\t" + str(unshiftedStart)) + outfh.write("\t" + displayName) + outfh.write("\t" + ", ".join(pLoFList)) + outfh.write("\t" + ", ".join(pLoFFlags)) + outfh.write("\t" + "\t".join(pLoFCuration)) if extraFh: - extraFh.write("\t".join(name + hgvscList + hgvspList + maybeExtraFields)) + extraFh.write(", ".join(hgvscList) + "\t" + ", ".join(hgvspList) + "\t" + "\t".join(maybeExtraFields)) extraFh.write("\n") else: - outfh.write("\t" + "\t".join([name] + hgvscList + hgvspList + maybeExtraFields)) + outfh.write("\t" + ", ".join(hgvscList)) + outfh.write("\t" + ", ".join(hgvspList)) + outfh.write("\t" + "\t".join(maybeExtraFields)) outfh.write("\n") def parseLofFile(fpath): """Make a struct of the different loss of function flags for a curated variant.""" gotHeader = False lofHeader = [] ret = {} with open(fpath) as fh: for line in fh: if not gotHeader: lofHeader = line.strip().split("\t") gotHeader = True else: lofDetails = line.strip().split("\t") ret[lofDetails[0]] = {lofHeader[x]: lofDetails[x] for x in range(len(lofHeader))} return ret def main(): args = parseCommandLine() lofDict = {} lofFile = args.lofFilePath extraFh = None if lofFile: lofDict = parseLofFile(lofFile) if args.infile == "stdin": infh = sys.stdin else: infh = open(args.infile) if args.outfile == "stdout": outfh = sys.stdout else: outfh = open(args.outfile, "w") if args.extra_output_file: if args.extra_output_file == "stdout": extraFh = sys.stdout else: extraFh = open(args.extra_output_file, "w") gnomadVcfBedToBigBed(infh, outfh, extraFh, args.version, lofDict) infh.close() outfh.close() if __name__ == "__main__": main()