def init(filename, __EXCLUDE_PSEUDOGENES=0):
global __geneDB, __symbols, __gene_symbol_parents, __gene_symbol_synonyms
__geneDB = pyCSV()
__geneDB.load(filename,"\t")
for row in xrange(1, __geneDB.rows+1):
if __EXCLUDE_PSEUDOGENES and __geneDB.get(row, 2).count("pseudogene")>0:
continue
symbol = geneUtils.formatGeneSymbol(__geneDB.get(row, 1))
__original_names[symbol] = __geneDB.get(row, 1)
__symbols.add(symbol)
__sym_rows[symbol] = row
if __isApproved(symbol):
__approved_symbols.add(symbol)
print "Loaded:", len(__approved_symbols), "approved gene symbols..."
for symbol in __approved_symbols:
past_symbols = getPastSymbols(symbol)
for child in past_symbols:
try:
__gene_symbol_parents[child].add(symbol)
except KeyError:
__gene_symbol_parents[child] = set([symbol])
for synSym in getSynonyms(symbol):
try:
__gene_symbol_synonyms[synSym].add(symbol)
except KeyError:
__gene_symbol_synonyms[synSym] = set([symbol])
for symbol in __gene_symbol_synonyms:
remove = []
for synGene in __gene_symbol_synonyms[symbol]:
if synGene not in __approved_symbols:
remove.append(synGene)
for r in remove:
__gene_symbol_synonyms[symbol].remove(r)
def mapTargetNames(targets_file,
__ENABLE_GENE_UPDATES=1,
__ENABLE_GENE_VERIFICATION=1):
global __targets_unnamed, __targets, __target_names, __geneSet
__targetCatalogue = pyCSV()
__targetCatalogue.load(targets_file)
rejectednames = 0
representedids = set([])
for r in xrange(1, __targetCatalogue.rows + 1):
targetId = int(__targetCatalogue.get(r, 0))
targetGene = geneUtils.formatGeneSymbol(__targetCatalogue.get(r, 2))
representedids.add(targetId)
if targetGene != None:
parentSym = geneDB.findUpdatedSymbol(targetGene)
if __ENABLE_GENE_UPDATES and parentSym != None:
if __DEBUG > 1:
print "Updated:", targetGene, "to:", parentSym
targetGene = parentSym
if __ENABLE_GENE_VERIFICATION and not geneDB.isApproved(
targetGene):
if __DEBUG > 1:
print "Rejected:", targetGene
rejectednames += 1
continue
__geneSet.add(targetGene)
__target_names[targetId] = targetGene
for targetId in __targets:
if targetId not in __target_names.keys():
__targets_unnamed += 1
if __DEBUG > 0:
print "Rejected: ", rejectednames
print "Unrepresented: ", len(set(__targets.keys()) - representedids)
__drugSet = set([])
for drugbankid in __drugs:
drug = __drugs[drugbankid]
for target in drug['targets']:
targetId = target['partner']
if targetId in __target_names:
targetGene = __target_names[targetId]
__drugSet.add(drugbankid)
try:
__drugDict[targetGene].add(drugbankid)
except KeyError:
__drugDict[targetGene] = set([drugbankid])
removable_drugs = set([])
for drugbankid in __drugs:
if drugbankid not in __drugSet:
removable_drugs.add(drugbankid)
for drugbankid in removable_drugs:
del __drugs[drugbankid]
lenbefore = len(__geneSet)
__geneSet = __geneSet & set(__drugDict.keys())
lenafter = len(__geneSet)
if __DEBUG > 0:
print "Removed", (lenafter - lenbefore), "untargeted gene names"
print "Total drugs with targets: ", len(__drugSet), len(__drugs)
print "Total geneset size: ", len(__geneSet)
def mapTargetNames(targets_file,__ENABLE_GENE_UPDATES=1,__ENABLE_GENE_VERIFICATION=1):
global __targets_unnamed, __targets, __target_names, __geneSet
__targetCatalogue = pyCSV()
__targetCatalogue.load(targets_file)
rejectednames = 0
representedids = set([])
for r in xrange(1, __targetCatalogue.rows+1):
targetId = int(__targetCatalogue.get(r,0))
targetGene = geneUtils.formatGeneSymbol(__targetCatalogue.get(r,2))
representedids.add(targetId)
if targetGene != None:
parentSym = geneDB.findUpdatedSymbol(targetGene)
if __ENABLE_GENE_UPDATES and parentSym != None:
if __DEBUG>1:
print "Updated:", targetGene, "to:", parentSym
targetGene = parentSym
if __ENABLE_GENE_VERIFICATION and not geneDB.isApproved(targetGene):
if __DEBUG>1:
print "Rejected:", targetGene
rejectednames+=1
continue
__geneSet.add(targetGene)
__target_names[targetId] = targetGene
for targetId in __targets:
if targetId not in __target_names.keys():
__targets_unnamed += 1
if __DEBUG>0:
print "Rejected: ", rejectednames
print "Unrepresented: ", len(set(__targets.keys()) - representedids)
__drugSet = set([])
for drugbankid in __drugs:
drug = __drugs[drugbankid]
for target in drug['targets']:
targetId = target['partner']
if targetId in __target_names:
targetGene = __target_names[targetId]
__drugSet.add(drugbankid)
try:
__drugDict[targetGene].add(drugbankid)
except KeyError:
__drugDict[targetGene] = set([drugbankid])
removable_drugs = set([])
for drugbankid in __drugs:
if drugbankid not in __drugSet:
removable_drugs.add(drugbankid)
for drugbankid in removable_drugs:
del __drugs[drugbankid]
lenbefore = len(__geneSet)
__geneSet = __geneSet & set(__drugDict.keys())
lenafter = len(__geneSet)
if __DEBUG>0:
print "Removed", (lenafter - lenbefore), "untargeted gene names"
print "Total drugs with targets: ", len(__drugSet), len(__drugs)
print "Total geneset size: ", len(__geneSet)
def loadEvolutionaryGenes(filename, __ENABLE_GENE_VERIFICATION=0,
__ENABLE_GENE_UPDATES=0, __CROSS_MATCH_LEVEL = 1, include_studies = [1,2,3,4,5]):
global __DEBUG
genesTSV = pyCSV()
genesTSV.load(filename, "\t")
bustamante = []
vamathevan_human = []
kosiol_human = []
if 1 in include_studies:
bustamante = [item.lower() for item in geneUtils.columnToList(genesTSV, 1, 2)]
if 2 in include_studies:
vamathevan_human = [item.lower() for item in geneUtils.columnToList(genesTSV, 3, 2)]
if 3 in include_studies:
kosiol_human = [item.lower() for item in geneUtils.columnToList(genesTSV, 8, 2)]
conflicts = []
bakewell = []
nielsen = []
if 4 in include_studies:
bakewell, c = geneUtils.mergeColumns(genesTSV, 12, 13, 2)
bakewell = [item.lower() for item in bakewell]
conflicts.extend(c)
if 5 in include_studies:
nielsen, c = geneUtils.mergeColumns(genesTSV, 17, 18, 2)
nielsen = [item.lower() for item in nielsen]
conflicts.extend(c)
# verify gene symbols
duplicates = 0
geneCounts = {}
geneUtils.geneFrequency(geneCounts, bustamante)
geneUtils.geneFrequency(geneCounts, vamathevan_human)
geneUtils.geneFrequency(geneCounts, kosiol_human)
geneUtils.geneFrequency(geneCounts, bakewell)
geneUtils.geneFrequency(geneCounts, nielsen)
#duplicates+=geneUtils.addAll(geneSet, bustamante)
#duplicates+=geneUtils.addAll(geneSet, vamathevan_human)
#duplicates+=geneUtils.addAll(geneSet, kosiol_human)
#duplicates+=geneUtils.addAll(geneSet, bakewell)
#duplicates+=geneUtils.addAll(geneSet, nielsen)
if __ENABLE_GENE_VERIFICATION:
for pair in conflicts:
g1 = pair[0].lower()
g2 = pair[1].lower()
if __ENABLE_GENE_UPDATES:
g1parent = geneDB.findUpdatedSymbol(g1)
g2parent = geneDB.findUpdatedSymbol(g2)
if g1parent != None:
g1 = g1parent
if g2parent != None:
g2 = g2parent
if geneDB.isApproved(g1):
if __DEBUG>1:
print "Gene", g2, "not approved, but",g1,"is fine"
try:
geneCounts[g1]+=1
except KeyError:
geneCounts[g1] = 1
elif geneDB.isApproved(g2):
if __DEBUG>1:
print "Gene", g1, "not approved, but",g2,"is fine"
try:
geneCounts[g2]+=1
except KeyError:
geneCounts[g2] = 1
else:
if __DEBUG>1:
print "Neither",g1,"nor",g2,"are valid"
else:
for pair in conflicts:
g1 = pair[0].lower()
g2 = pair[1].lower()
try:
geneCounts[g2]+=1
except KeyError:
geneCounts[g2] = 1
duplicates, geneSet = geneUtils.addFilterFrequency(geneCounts, __CROSS_MATCH_LEVEL)
ofile = open(os.sep.join(["results","log","geneSetDuplicateFrequency.txt"]),'w')
glist = []
for gene in geneCounts:
glist.append((gene, geneCounts[gene]))
for item in sorted(glist, key=lambda item: -item[1]):
ofile.write("%-20s%d\n" % item)
ofile.close()
geneSet = set([geneUtils.formatGeneSymbol(geneSym) for geneSym in geneSet])
if __ENABLE_GENE_UPDATES:
geneUtils.updateGeneSet(geneSet)
if __ENABLE_GENE_VERIFICATION:
geneUtils.removeInvalidGenes(geneSet)
if __DEBUG>0:
print "\n-----------------------------"
print "Total Duplicates: ", duplicates
print "Total Name Conflicts: ", len(conflicts)
print "Total Genes Remaining: ", len(geneSet)
print "-----------------------------\n"
log_file = open(os.sep.join(["results","log","loaded_genelist.txt"]),'w')
for gene in geneSet:
log_file.write(gene+"\n")
log_file.close()
return geneSet
def init(filename, __ENABLE_GENE_VERIFICATION = 0, __ENABLE_GENE_UPDATES = 0, __INCLUDE_MAPPED_GENES = 0, trait_exclude_file = 0, pfilter = 0.05):
global __DEBUG, __pValues, __gwasCatalogue, __studyByTrait, __geneSet, __traitDict, __studyByGene
exclude_traits = set([])
if trait_exclude_file != 0:
ifile = open(trait_exclude_file,'r')
for line in ifile:
exclude_traits.add(line.strip())
ifile.close()
__gwasCatalogue.load(filename, "\t")
invalidGeneSet = set([])
updatedGeneSet = set([])
for i in xrange(1, __gwasCatalogue.rows+1):
geneString = __gwasCatalogue.get(i, 13).strip()
geneTrait = __gwasCatalogue.get(i, 7).strip()
pvalueText = __gwasCatalogue.get(i, 27)
pvalue = 0
try:
pvalue = float(pvalueText)
except ValueError:
pvalue = -1
if pvalue > pfilter:
continue
if geneTrait in exclude_traits:
continue
if geneString==None:
continue
if geneString == "":
continue
__pValues[i] = pvalue
try:
__studyByTrait[geneTrait].add(i)
except KeyError:
__studyByTrait[geneTrait] = set([i])
geneItems = geneString.split(",")
for item in geneItems:
geneSymbols = item.split(" - ")
for geneSym in geneSymbols:
geneSym = geneUtils.formatGeneSymbol(geneSym.strip())
__addGene(i,geneSym, geneTrait, __ENABLE_GENE_VERIFICATION, __ENABLE_GENE_UPDATES, updatedGeneSet, invalidGeneSet)
if __INCLUDE_MAPPED_GENES:
mappedGenes = __gwasCatalogue.get(i, 14)
mappedItems = mappedGenes.split(";")
for item in mappedItems:
geneSymbols = item.split(" - ")
for geneSym in geneSymbols:
geneSym = geneUtils.formatGeneSymbol(geneSym)
__addGene(i,geneSym, geneTrait, __ENABLE_GENE_VERIFICATION, __ENABLE_GENE_UPDATES, updatedGeneSet, invalidGeneSet)
invalid_file = open(os.sep.join(["results","log","invalid_gwas.txt"]),'w')
for geneSym in invalidGeneSet:
invalid_file.write(geneSym+"\n")
invalid_file.close()
background_file = open(os.sep.join(["results", "log",
"gwas_background.txt"]), 'w')
for geneSym in __geneSet:
background_file.write(geneDB.__original_names[geneSym] + "\n")
background_file.close()
if __DEBUG > 0:
print "\n---------------------------------"
print "GWAS Invalid Gene Symbols: ", len(invalidGeneSet)
print "GWAS Updated Gene Symbols: ", len(updatedGeneSet)
print "GWAS Total Genes Remaining: ", len(__geneSet)
print "---------------------------------\n"
def getSynonyms(geneSym):
global __geneDB, __sym_rows, __synonyms
return [geneUtils.formatGeneSymbol(item) for item in __strToList(__geneDB.get(__sym_rows[geneSym.lower()], __synonyms))]
def initTargets(targets_file, protein_file,__ENABLE_GENE_VERIFICATION=0, __ENABLE_GENE_UPDATES=0):
global __DEBUG, __targetCatalogue, __geneSet, __geneNames, __drugDict
__targetCatalogue.load(targets_file)
rejectedSet = set([])
updatedSet = set([])
for r in xrange(1, __targetCatalogue.rows+1):
geneId = int(__targetCatalogue.get(r,0))
geneName = geneUtils.formatGeneSymbol(__targetCatalogue.get(r,2))
if geneName != None:
if __ENABLE_GENE_UPDATES:
parentSym = geneDB.findUpdatedSymbol(geneName)
if parentSym != None:
updatedSet.add(geneName)
geneName = parentSym
if __ENABLE_GENE_VERIFICATION and not geneDB.isApproved(geneName):
if __DEBUG>2 and geneName != "" or geneName == "papc":
print "Rejected:", geneName
rejectedSet.add(geneName)
continue
__geneNames[geneId] = geneName
__geneSet.add(geneName)
__drugDict[geneName] = set([])
invalid_file = open(os.sep.join(["results","log","invalid_drugbank.txt"]),'w')
for geneName in rejectedSet:
invalid_file.write(geneName+"\n")
invalid_file.close()
proteins = parseFASTA(protein_file)
__drugSet = set([])
empty_gene_drug_targets = 0
for fasta in proteins:
items = fasta[1].split()
geneId = int(items[0])
if geneId in __geneNames:
parenthetical = fasta[1][fasta[1].rfind("(")+1 : fasta[1].rfind(")")]
drugs = parenthetical.split(";")
for drug in drugs:
drugbankid = drug.strip()
__drugDict[__geneNames[geneId]].add(drugbankid)
__drugSet.add(drugbankid)
removable = set([])
for gene in __geneSet:
if gene not in __drugDict or len(__drugDict[gene]) == 0:
removable.add(gene)
empty_gene_drug_targets += 1
__geneSet -= removable
removable_drugs = set([])
for drugbankid in __drugs:
if drugbankid not in __drugSet:
removable_drugs.add(drugbankid)
for drugbankid in __drugSet:
if drugbankid not in __drugs:
__drugs[drugbankid] = {'name':drugbankid}
for drugbankid in removable_drugs:
del __drugs[drugbankid]
if __DEBUG>0:
print "\n------------------------------------------"
print "Invalid Drug Target Gene Symbols: ", len(rejectedSet)
print "Updated Drug Target Gene Symbols: ", len(updatedSet)
print "Remaining Drug Target Gene Symbols: ", len(__geneSet)
print "Drugs with targets: ", len(__drugSet), len(__drugs)
print "Removed:", empty_gene_drug_targets, "genes without targeting drugs"
print "------------------------------------------\n"
