def query(release, user, pword, host, port):
import getIntactDict
import queryPDB
import coordMap
import parseUniChem
## Create the pdbDict which stores all the relevant information. The moldict
## is a look-up molDict[molregno] = cmpdId. Coordmap is a dictionary with the
## coordinate mappings between pdbe and uniprot.
uniDict = parseUniChem.parse('data/unichemMappings.txt')
coordMap = coordMap.coordMap('data/pdb_chain_uniprot.csv')
intactDict = getIntactDict.getIntacts(uniDict, release, user, pword, host,
port)
pdbDict = queryPDB.queryPDB(uniDict, intactDict, coordMap, release)
return pdbDict
def query(release, user, pword, host, port):
import getIntactDict
import queryPDB
import coordMap
import parseUniChem
## Create the pdbDict which stores all the relevant information. The moldict
## is a look-up molDict[molregno] = cmpdId. Coordmap is a dictionary with the
## coordinate mappings between pdbe and uniprot.
uniDict = parseUniChem.parse('data/unichemMappings.txt')
coordMap = coordMap.coordMap()
intactDict = getIntactDict.getIntacts(uniDict, release, user, pword, host, port)
pdbDict = queryPDB.queryPDB(uniDict, intactDict, coordMap, release)
return pdbDict
def analysis(th, release, user, pword, host, port):
####
#### Load data.
####
## Set threshold for all calculations.
import numpy as np
threshold = -np.log10(th*10**(-6))
## Get all ChEMBL targets with a Uniprot accession.
import getUniprotTargets
chemblTargets = getUniprotTargets.getUniprotTargets(release, user, pword, host, port)
## Read all human protein coding genes
import parse
humProtCod = parse.parse2col('data/proteinCoding.tab', True, 1, 0)
#humanTargets = humanProtCodUniq.keys()
print "We are dealing with %s human proteins" %len(humProtCod.keys())
## Get a list of all human (!) ChEMBL targets
humChembl = {}
for target in chemblTargets:
if target in humProtCod.keys():
humChembl[target] = 0
## Load the pfamDict.
import pickle
inFile = open('data/protCodPfamDict_%s.pkl' %release, 'r')
pfamDict = pickle.load(inFile)
inFile.close()
## Load the pdbDict.
import pickle
infile = open('data/pdbDict_chembl%s.pkl' %release, 'r')
pdbDict = pickle.load(infile)
infile.close()
## Load the uniprotDict.
import pickle
infile = open('data/bsDictUniprot_chembl%s.pkl'%release, 'r')
uniprotDict = pickle.load(infile)
infile.close()
print 'number of targets with binding site information', len(uniprotDict.keys())
## Load the uniDict.
import parseUniChem
uniDict = parseUniChem.parse('data/unichemMappings.txt')
## Load the propDict.
import pickle
infile = open('data/propDict_%s.pkl'% release, 'r')
propDict = pickle.load(infile)
infile.close()
####
#### Generate Plots.
####
## For each target in PfamDict, calculate the ratio of domain over non-domain regions.
import getRatioUnstruct
import writeTable
import os
pfamDict = getRatioUnstruct.getRatio(pfamDict, humProtCod, release, user, pword, host, port)
writeTable.writePfam(pfamDict, humProtCod,humChembl, chemblTargets, release)
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s plotPfamStat.R' %release)
## Assess small molecule binding within Pfam domains for PDBe entries.
import matchData
import evaluatePred
pdbDict = matchData.pdbe(pdbDict,pfamDict, release)
evaluatePred.pdbe(pdbDict, 'within', release)
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R' % ('within', "PDB" , release))
## Assess small molecule binding within Pfam domains for Uniprot entries.
import matchData
import evaluatePred
uniprotDict = matchData.uniprot(uniprotDict,pfamDict, release)
evaluatePred.uniprot(uniprotDict, 'within', release)
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R' % ('within', "Uni" , release))
## Print a summary of the number of targets and domains covered by the mapping.
import groupSize
import os
allDomains = groupSize.uniqueDomains(pfamDict)
singleDomains = groupSize.singles(chemblTargets, pfamDict)
groupsAll = groupSize.groupSize(chemblTargets, pfamDict, singles)
print "all possible groups (single, none, multi, conflict):",groupsAll
(single, multi, conflict) = groupSize.groupSizeMap(chemblTargets, release, user , pword, host, port)
print "all covered targets (single, multi, conflict): ", len(single), len(multi), len(conflict)
(single, multi, conflict) = groupSize.actSizeMap(chemblTargets, release, user , pword, host, port)
print "all covered targets (single, multi, conflict): ", len(single), len(multi),len(conflict)
## Plot the evaluation of the mappings.
import queryDevice
import matchData
import evaluatePred
import os
intacts = queryDevice.queryDevice("SELECT mpf.protein_accession,mpf.domain,mpf.molregno, pfd.start, pfd.end, mpf.maptype, md.chembl_id FROM map_pfam mpf JOIN pfam_domains pfd ON pfd.protein_accession = mpf.protein_accession JOIN molecule_dictionary md ON md.molregno = mpf.molregno WHERE mpf.domain = pfd.domain", release, user, pword, host, port)
# ...against PDBe
pdbDict = matchData.pdbePredicted(pdbDict, intacts, uniDict)
evaluatePred.pdbePredicted(pdbDict, 'prediction', release)
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R' % ('prediction', 'PDB' , release))
# ...against uniprot
uniprotDict = matchData.uniprotPredicted(uniprotDict, intacts)
evaluatePred.uniprotPredicted(uniprotDict, 'prediction', release)
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R' % ('prediction', "Uni" , release))
## Map the overlap
#import overlap
#tholds = [50,10,5,1,0.5,0.1,0.05,0.01,0.005,0.001, 0.0005,0.0001, 0.00005,0.000001]
#overlap.overlap(propDict, tholds, release)
## Power Law Distribution of domain occurences
## Prepare the data for the power law plot.
## 1. Count the targets and compounds per domain using the propDict
## 2. Count a human genes per domain using the Pfam dictionary
## 3. Plot the power law distributions for all domains and overlay 25 most
## frequent domains
import countFreqs
import plplot
import plplotRaw
import parse
countFreqs.countLigs(humProtCod.keys(), chemblTargets, release ,user, pword, host, port)
countFreqs.countDoms(humProtCod.keys(), pfamDict)
filenames = ['genFreq.tab', 'domLigs.tab', 'targLigs.tab']
for filename in filenames:
os.system('/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s statPowerLaw.R' %filename)
al, minx = parse.rdstatLogs('data/powerLawLog%s' % filename)
freqs = parse.col2intlist('data/%s'%filename, 1, True)
print len(freqs), minx, al, filename, type(freqs), type(freqs[1])
plplot.plplot(freqs, minx, al, filename)
plplotRaw.plplotRaw(freqs, filename)
## Plot the ligand properties.
import export
import os
selected = ['Pkinase','Pkinase_Tyr','p450','SNF','Trypsin', 'RVP']
export.exportProps(selected,propDict, threshold, release, user, pword, host, port)
filename = 'data/cmpdProps_pKi%s_chembl%s.tab'%(int(threshold), release)
os.system("/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s pca.R"%filename)
def analysis(release):
####
#### Load parameters.
####
import yaml
# Read config file.
paramFile = open('mpf.yaml')
params = yaml.safe_load(paramFile)
user = params['user']
pword = params['pword']
host = params['host']
port = params['port']
th = params['threshold']
####
#### Load data.
####
## Set threshold for all calculations.
import numpy as np
threshold = -np.log10(th * 10**(-6))
## Get all ChEMBL targets with a Uniprot accession.
import getUniprotTargets
chemblTargets = getUniprotTargets.getUniprotTargets(
release, user, pword, host, port)
## Get a list of all human (!) ChEMBL targets
humChembl = {}
for target in chemblTargets.keys():
if chemblTargets[target] == 'H**o sapiens':
humChembl[target] = 0
## Read all human protein coding genes
import parse
humProtCod = parse.parse2col('data/proteinCoding.tab', True, 1, 0)
#humanTargets = humanProtCodUniq.keys()
print "We are dealing with %s human proteins" % len(humProtCod.keys())
## Load the pfamDict.
import pickle
inFile = open('data/protCodPfamDict_%s.pkl' % release, 'r')
pfamDict = pickle.load(inFile)
inFile.close()
## Load the pdbDict.
import pickle
infile = open('data/pdbDict_%s.pkl' % release, 'r')
pdbDict = pickle.load(infile)
infile.close()
## Load the uniprotDict.
import pickle
infile = open('data/bsDictUniprot_%s.pkl' % release, 'r')
uniprotDict = pickle.load(infile)
infile.close()
print 'number of targets with binding site information', len(
uniprotDict.keys())
## Load the uniDict.
import parseUniChem
uniDict = parseUniChem.parse('data/unichemMappings.txt')
## Load the propDict.
import pickle
infile = open('data/propDict_%s.pkl' % release, 'r')
propDict = pickle.load(infile)
infile.close()
####
#### Generate Plots.
####
## For each target in PfamDict, calculate the ratio of domain over non-domain regions.
import getRatioUnstruct
import writeTable
import os
pfamDict = getRatioUnstruct.getRatio(pfamDict, humProtCod, release, user,
pword, host, port)
writeTable.writePfam(pfamDict, humProtCod, humChembl, chemblTargets,
release)
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s plotPfamStat.R'
% release)
## Assess small molecule binding within Pfam domains for PDBe entries.
import matchData
import evaluatePred
pdbDict = matchData.pdbe(pdbDict, pfamDict, release)
evaluatePred.pdbe(pdbDict, 'within', release)
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R'
% ('within', "PDB", release))
## Assess small molecule binding within Pfam domains for Uniprot entries.
import matchData
import evaluatePred
uniprotDict = matchData.uniprot(uniprotDict, pfamDict, release)
evaluatePred.uniprot(uniprotDict, 'within', release)
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R'
% ('within', "Uni", release))
## Print a summary of the number of targets and domains covered by the mapping.
import groupSize
import os
allDomains = groupSize.uniqueDomains(pfamDict)
singleDomains = groupSize.singles(chemblTargets, pfamDict)
groupsAll = groupSize.groupSize(chemblTargets, pfamDict, singles)
print "all possible groups (single, none, multi, conflict):", groupsAll
(single, multi, conflict) = groupSize.groupSizeMap(chemblTargets, release,
user, pword, host, port)
print "all covered targets (single, multi, conflict): ", len(single), len(
multi), len(conflict)
(single, multi, conflict) = groupSize.actSizeMap(chemblTargets, release,
user, pword, host, port)
print "all covered targets (single, multi, conflict): ", len(single), len(
multi), len(conflict)
## Plot the evaluation of the mappings.
import queryDevice
import matchData
import evaluatePred
import os
intacts = queryDevice.queryDevice(
"""SELECT mpf.protein_accession,
mpf.domain,mpf.molregno, pfd.start, pfd.end, mpf.maptype,
md.chembl_id FROM map_pfam mpf
JOIN pfam_domains pfd
ON pfd.protein_accession = mpf.protein_accession
JOIN molecule_dictionary md
ON md.molregno = mpf.molregno
WHERE mpf.domain = pfd.domain""", release, user, pword, host, port)
# ...against PDBe
pdbDict = matchData.pdbePredicted(pdbDict, intacts, uniDict)
evaluatePred.pdbePredicted(pdbDict, 'prediction', release)
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R'
% ('prediction', 'PDB', release))
# ...against uniprot
uniprotDict = matchData.uniprotPredicted(uniprotDict, intacts)
evaluatePred.uniprotPredicted(uniprotDict, 'prediction', release)
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s -%s -%s ecdf.R'
% ('prediction', "Uni", release))
## Map the overlap
#import overlap
#tholds = [50,10,5,1,0.5,0.1,0.05,0.01,0.005,0.001, 0.0005,0.0001, 0.00005,0.000001]
#overlap.overlap(propDict, tholds, release)
## Power Law Distribution of domain occurences
## Prepare the data for the power law plot.
## 1. Count the targets and compounds per domain using the propDict
## 2. Count a human genes per domain using the Pfam dictionary
## 3. Plot the power law distributions for all domains and overlay 25 most
## frequent domains
import countFreqs
import plplot
import plplotRaw
import parse
countFreqs.countLigs(humProtCod.keys(), chemblTargets, release, user,
pword, host, port)
countFreqs.countDoms(humProtCod.keys(), pfamDict)
filenames = ['genFreq.tab', 'domLigs.tab', 'targLigs.tab']
for filename in filenames:
os.system(
'/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s statPowerLaw.R'
% filename)
al, minx = parse.rdstatLogs('data/powerLawLog%s' % filename)
freqs = parse.col2intlist('data/%s' % filename, 1, True)
print len(freqs), minx, al, filename, type(freqs), type(freqs[1])
plplot.plplot(freqs, minx, al, filename)
plplotRaw.plplotRaw(freqs, filename)
## Plot the ligand properties.
import export
import os
selected = ['Pkinase', 'Pkinase_Tyr', 'p450', 'SNF', 'Trypsin', 'RVP']
export.exportProps(selected, propDict, threshold, release, user, pword,
host, port)
filename = 'data/cmpdProps_pKi%s_chembl%s.tab' % (int(threshold), release)
os.system(
"/ebi/research/software/Linux_x86_64/bin/R-2.11.0 CMD BATCH --vanilla -%s pca.R"
% filename)
