def reactionBounds(self,model,reactionName,objDir = -1.0):
solver = LPSolver()
posObjective = {reactionName:objDir}
negObjective = {reactionName:1.0*objDir}
posPrediction = solver.run(model,posObjective)
posValue = posPrediction[reactionName]
negPrediction = solver.run(model,negObjective)
negValue = negPrediction[reactionName]
return (negValue,posValue)
def findBoundaryProduction(originalModel, bounds, combiLimits, objectiveName, productionName):
model = LinearModel()
model.extend(originalModel)
if combiLimits != None:
for (targetValues,limit) in combiLimits:
model = addCombinationLimit(model, targetValues,limit)
#objectiveMap = {objectiveName:-1.0}
objectiveMap = {productionName:1.0}
model.addColumnLimits(bounds)
lp = LPSolver()
fluxMap = lp.run(model,objectiveMap)
objectiveValue = fluxMap[objectiveName]
productionValue = fluxMap[productionName]
return (fluxMap,objectiveValue,productionValue)
def exportMetabolite(self,model,metaboliteName,max=1e3):
solver= LPSolver()
exportTag = "EX_test_export"
reaction = {metaboliteName:-1.0}
objective = {exportTag:-1.0}
model.addColumn(exportTag,reaction)
model.addColumnLimit(exportTag,(0.0,max))
prediction = solver.run(model,objective)
exportValue = prediction[exportTag]
model.removeColumn(exportTag)
return exportValue
def simpleTestOpt(con,originalModel,controlTargets,naturalObjectiveName,syntheticObjectiveName,verbose = False,naturalCoefficient=-0.05):
'''
Optimiztaion Tester for depdenency anlaysis
Construciton object contains union of all libraries which are used by target sets.
'''
gRMap = con.getGeneTargetMap()
regulationLibrary = con.regulationLibrary
objective = {}
for (lib,prefix,target) in controlTargets:
if gRMap != None:
if target in gRMap.keys():
targets = gRMap[target]
else:
print "target %s not found in gene map" % (target)
targets = [target]
else:
targets = [target]
for target in targets:
if lib in regulationLibrary.keys():
if target in con.regulationLibrary[lib].keys():
controlValue = con.regulationLibrary[lib][target]
objective[target] = -1.0 * controlValue
iObjective = dict(objective)
objective[naturalObjectiveName] = naturalCoefficient
lp = LPSolver()
prediction = lp.run(originalModel, objective= objective)
rObjective = iObjective
if verbose: print "Current objective[%s]: %s" % (str(len(iObjective)),iObjective)
(iGeneObjective,iOtherObjective) = (None,None)
if originalModel.controlMap != None:
(iGeneObjective,iOtherObjective) = originalModel.printGeneObjective(iObjective)
if verbose: print "Current Genetic objective[%s]: %s" % (str(len(iGeneObjective)),iGeneObjective)
if verbose: print "Current Other objective: %s" % (iOtherObjective)
rObjective = iGeneObjective
lp.clear()
del lp
return (prediction,rObjective)
def checkSolverScip(self,modelMatrix,predVal,delta=1e-3):
lp = LPSolver()
lp.setModel(modelMatrix)
lp.runIntOpt()
scipPredVal = lp.getMipPredictionMap()
(testRows,badRows) = self.checkValues(modelMatrix.data,scipPredVal,modelMatrix.getRowLimits())
if self.verbose: print "--Debug: number of failed rows %s" % (len(badRows))
lp.clear()
solverDiff = self.debugCompareFluxes(predVal,scipPredVal)
if self.verbose: print "--Debug: difference in glpk / scip %s" % (len(solverDiff))
return (testRows,badRows,solverDiff)
def main_function():
parser = OptionParser()
parser.add_option("-v", "--verbose", action="store_true", dest="verbose", default=False, help="set verbose mode")
parser.add_option(
"--config",
type="string",
metavar="FILE",
dest="config",
default="redirector.config",
help="Master configuration file that provides most setting for the Flux Balanace Analysis. Extra variable settings will be ingnored. Hence the same config can be used for multiple analysis functions",
)
parser.add_option(
"-c",
"--modelConfig",
type="string",
metavar="FILE",
dest="configFileName",
default="model_config.txt",
help="Configuration file which sets model files",
)
parser.add_option(
"-n",
"--configNames",
type="string",
metavar="String",
dest="configNames",
default="Default",
help="A comma separated list of the names of configurations to use, as set out in the configuration file",
)
parser.add_option(
"-m",
"--modelname",
type="string",
metavar="String",
dest="modelName",
default="",
help="Name of model(s) from the modelconfiguration file",
)
parser.add_option(
"-b",
"--bioObjective",
type="string",
dest="bioObj",
default="Biomass",
help="Name / ID of biological objective reaction",
metavar="String",
)
parser.add_option(
"-o",
"--outputfile",
dest="outputFileName",
default=None,
help="Name of report file to be generated",
metavar="FILE",
)
parser.add_option(
"-r",
"--result_directory",
type="string",
metavar="directory",
dest="resultDirectory",
default="../../results/",
help="Directory where results are stored",
)
parser.add_option(
"--targets",
type="string",
metavar="String",
dest="targets",
default="",
help="List of valid reaction target, if left blank will be automatically filled in from metabolic network file",
)
parser.add_option(
"--report",
action="store_true",
dest="isReport",
default=False,
help="When this tag is used a report will be generated when the analysis is finished",
metavar="boolean",
)
parser.add_option("--debug", action="store_true", dest="debug", default=False, help="turn on debug mode")
parser.add_option("--gm", "--GeneMap", action="store_true", dest="useGeneMap", default=False, help="Use Gene Map")
parser.add_option(
"--section",
type="string",
metavar="String",
dest="subSections",
default="",
help="Comma separated list of sections of the model files to use",
)
# -------------------------------
# Parse options
# -------------------------------
(options, args) = parser.parse_args()
config = ReflectionConfig()
config.readfp(open("Redirector.config"))
# ---------------------------
# configure preset analysis
# ---------------------------
configNames = options.configNames.split(",")
configNames.insert(0, "Redirector Model")
for name in configNames:
config.merge(name, "Redirector", append=True)
# ----------------------------------------
# reflect options from configuration
# ----------------------------------------
config.reflect("Redirector", options)
config.load("Redirector", options.__dict__, override=False)
# -----------------------------------------
# Check and Build Storage Directories
# -----------------------------------------
dataDirectory = config.getValue("Redirector", "dataDirectory", classType="".__class__)
resultsDirectory = config.getValue("Redirector", "resultDirectory", classType="".__class__)
analysisDirectory = config.getValue("Redirector", "analysisDirectory", classType="".__class__)
if not os.path.exists(dataDirectory):
raise IOError("unable to find required data directory" % dataDirectory)
if not os.path.exists(resultsDirectory):
os.makedirs(resultsDirectory)
if not os.path.exists(analysisDirectory):
os.makedirs(analysisDirectory)
# ----------------------------
# Parse Inputs
# ----------------------------
verbose = options.verbose
modelName = options.modelName
objectiveName = options.bioObj
outputFileName = options.outputFileName
"""
#----------------------------------------------------
# Initialize and set values for tools and factories
#----------------------------------------------------
"""
naturalObjective = {objectiveName: -1.0}
if verbose:
print "Flux Balanace Analysis Version 1.6"
if verbose:
print "Model names: [%s]" % (modelName)
if verbose:
print "Parsing data files for [%s]" % (modelName)
"""
I. Parse data files and configuration settings
"""
if verbose:
print "----------------Loading Metabolic Models---------------"
modelNames = modelName.split(",")
modelFactory = ModelFactory()
config.reflect("Redirector", modelFactory)
(fluxModel, modelMatrix, reducer, geneReduction) = modelFactory.loadModel(modelNames)
model = modelMatrix
if verbose:
print "removing objectives from target set"
targets = modelMatrix.targets
if verbose:
print "Targets List Size [%s]" % len(targets)
lps = LPSolver()
predictions = lps.run(model, naturalObjective)
objectiveValue = predictions[objectiveName]
lps.clear()
if verbose:
print "Optimized Objective [%s] Value [%s]" % (objectiveName, objectiveValue)
report = fluxModel.getReport()
report.addColumnHash("Flux", predictions)
if outputFileName == None or outputFileName == "":
outputFileName = resultsDirectory + "FBA_%s_%s.txt" % (modelName, strftime("%Y%m%dT%H%M%S"))
writer = ReportWriter()
writer.setFile(outputFileName)
writer.write(report)
writer.closeFile()
if verbose:
print "Report Written [%s]" % (outputFileName)
def productionLevels(originalModel,options,minBio=0.20,verbose=False):
naturalObjectiveName = options.bioObj
syntheticObjectiveName = options.synthObj
cellularObjective = {naturalObjectiveName:-1.0}
syntheticObjective = {syntheticObjectiveName:-1.0}
lo = LPSolver()
lo.setModel(originalModel)
oPredVal = lo.run(objective = cellularObjective)
oBioVal = oPredVal[naturalObjectiveName]
oSynthVal = oPredVal[syntheticObjectiveName]
if verbose: print "Max cellular: Biological [%s] Synthetic: [%s]" % (oBioVal, oSynthVal)
#---------------------------------------
# Values for Max Synthetic Objective
#---------------------------------------
sPredVal = lo.run(objective = syntheticObjective)
sBioVal = sPredVal[naturalObjectiveName]
sSynthVal = sPredVal[syntheticObjectiveName]
lo.clear()
if verbose: print "Max synthetic: Biological [%s] Synthetic: [%s]" % (sBioVal, sSynthVal)
#-----------------------------------
# Values for minimum Natural objective
#-----------------------------------
minObjVal = oBioVal*0.20
originalModel.addColumnLimit(naturalObjectiveName,(minObjVal,None))
lo = LPSolver()
s2PredVal = lo.run(model=originalModel,objective = syntheticObjective)
s2BioVal = s2PredVal[naturalObjectiveName]
s2SynthVal = s2PredVal[syntheticObjectiveName]
lo.clear()
return (oPredVal,sPredVal,s2PredVal)
def findControlDependencies(con,originalModel,controls,exclusion,options,searchSize=0,targetPrecent = 0.40,verbose = False,usePersist=False):
name = "".join(originalModel.modelName)
naturalObjectiveName = options.bioObj
syntheticObjectiveName = options.synthObj
controlTag = options.control
persistTag = "Dependency_persist_%s_%s_%s_%s_%s_%s" % (controlTag,name,naturalObjectiveName,syntheticObjectiveName,str(searchSize),str(targetPercent))
delta = 1e-4
iter = 0
iterSave = 100
completed = set()
controlSet = set()
controlMap = []
report = Report()
persistValue = None
if usePersist:
persistValue = loadPersist(persistTag)
if persistValue != None:
print "loading persisted dependency search"
(completed,controlMap,controlSet,report) = persistValue
controlSubSets = combinations(controls,searchSize)
xcontrolSubSets = set(controlSubSets)
xcontrolSubSets = xcontrolSubSets.difference(completed)
print "Control dependency depth [%s] search sets [%s]" % (searchSize,len(xcontrolSubSets))
lo = LPSolver()
sObjective = {syntheticObjectiveName:-1.0}
iPred = lo.run(model= originalModel, objective = sObjective)
synthVal = iPred[syntheticObjectiveName]
targetSVal = synthVal * targetPrecent
#print "Synthetic Target [%s] = %s * %s" % (targetSVal,synthVal,targetPercent)
controlMin = con.controlMin
controlMax = con.controlMax
con.controlMin = 0
con.controlMax = 0
targets = []
gRMap = con.getGeneTargetMap()
for (lib,prefix,target) in controls:
if gRMap != None:
if target in gRMap.keys():
rTargets = gRMap[target]
targets.extend(rTargets)
else:
targets.append(target)
#-----------------------------
# Run optimization
#-----------------------------
iter = 0
for controlSub in xcontrolSubSets:
iter += 1
completed.add(controlSub)
#Analysis of control
(prediction,objective) = simpleTestOpt(con, originalModel, controlSub, naturalObjectiveName,syntheticObjectiveName,verbose=False,naturalCoefficient=-0.5)
#Save results
syntheticFlux = prediction[syntheticObjectiveName]
#if verbose: print "Objective [%s]" % (objective)
#if verbose: print "Flux [%s]" % (prediction)
if syntheticFlux > targetSVal:
controlThresholds = controlThreshold([controlSub], exclusion)
if controlSub in controlThresholds.keys():
if syntheticFlux <= controlThresholds[controlSub] + delta:
#if verbose: print "no improvement"
continue
if verbose: print "Synthetic Production [%s]" % (syntheticFlux)
controlResultMap = originalModel.annotateGenes(objective,annotationName = "bnumber", regex="[a-zA-Z0-9\(\)]+")
controlTag = str(controlResultMap.keys())
controlSV = (controlSub,syntheticFlux)
controlSet.add(controlSV)
controlSV = (controlResultMap,syntheticFlux)
controlMap.append(controlSV)
#if verbose: print "Control Set [%s]" % (controlSub)
if verbose: print "Control Map [%s]" % (controlResultMap)
report.add(controlTag, "control values", controlResultMap)
report.add(controlTag, "production", syntheticFlux)
if iter % iterSave == 0:
print "persisting iteration %s" % (iter)
persistValue = (completed, controlSet,controlMap, report)
persist(persistTag, persistValue)
con.controlMin = controlMin
con.controlMax = controlMax
#Persist dependency search
if usePersist:
persistValue = (completed, controlSet,controlMap, report)
persist(persistTag, persistValue)
return (controlMap,controlSet,report)
def LinearModelVariableBoundarys(originalModel, objectiveName, targets=None, pickleFileName=None, strict=False, minObjectivePercent=None,searchSize=1):
'''
Find min and max boundaries for the dependent variables of a linear model.
Uses limitMap as constraints on model.
Add cumulative boundary persistence as pickle file function.
@param linearModel: linear model to be analyzed
@type linearModel: LinearModel
@param limitMap: map of variable names and lower and upper limits
@type limitMap: {variableName, (float, float)
@param targets: list of variables to perform analysis on
@type targets: list
@return: dictionary of lower and upper limits for each variable
@rtype: {variableName: (lowerlimit, upperlimit)}
'''
linearModel = LinearModel()
linearModel.extend(originalModel)
if pickleFileName != None:
if os.path.isfile(pickleFileName):
print "loading saved flux boundaries"
pFile = open(pickleFileName)
result = pickle.load(pFile)
pFile.close()
return result
originalLimits = linearModel.getColumnLimits()
originalObjectiveLimit = originalLimits[objectiveName]
objectiveVector = {objectiveName:-1.0}
solver = LPSolver()
originalValues = solver.run(model=linearModel, objective=objectiveVector)
originalObjectiveValue = originalValues[objectiveName]
if minObjectivePercent != None:
minObjectiveValue = originalObjectiveValue * minObjectivePercent
linearModel.addColumnLimit(objectiveName,(minObjectiveValue,None))
if targets == None:
targets = linearModel.getColumnNames()
targets.add(objectiveName)
print "Searching flux boundaries for %s > %s" % (objectiveName, minObjectiveValue)
result = {}
targetValues = targetValueCombinations(targets, [-1.0,1.0])
controlSubSets = combinations(targetValues,searchSize)
xcontrolSubSets = set(controlSubSets)
for name in targets:
nameTag = name
# if name not in linearModel.getColumnNames():
# print "target %s not found in model"
# print "boundary discovery not possible"
# continue
#for iTargetValues in xcontrolSubSets:
# name = "testControlValue"
# nameTag = iTargetValues
# linearModel = combinationLimitBuilder(linearModel, iTargetValues, name)
result[name] = (None,None)
negObjective = {name:1.0}
posObjective = {name:-1.0}
solver.clearObjective()
negValues = solver.run(linearModel, objective=negObjective)
negValue = negValues[name]
solver.clearObjective()
posValues = solver.run(linearModel, objective=posObjective)
posValue = posValues[name]
delta = 1e-4
if posValue != 0 or negValue !=0:
pass
if False:
originalValue = originalValues[name]
originalLimit = originalLimits[name]
if not (negValue - delta <= originalValue <= posValue + delta):
print "original value not in boundary"
print "objective value [%s] (%s) %s <= %s <= %s (%s)" % (name, originalLimit[0], negValue, originalValue, posValue, originalLimit[1])
#print "value neg code %s pos code %s" % (nscode, pscode)
(negValue,posValue) = (originalLimit[0],originalLimit[1])
else:
#print "objective value [%s] (%s) %s <= %s <= %s (%s)" % (name, originalLimit[0], negValue, originalValue, posValue, originalLimit[1])
pass
if negValue == None or negValue == float("-inf"):
continue
if posValue == None or posValue == float("-inf"):
continue
result[nameTag] = (negValue,posValue)
print "%s < [%s] < %s " % (negValue,nameTag,posValue)
if pickleFileName != None:
pFile = open(pickleFileName,'w')
pickle.dump(result, pFile)
pFile.close()
solver.clear()
del solver
linearModel.addColumnLimit(objectiveName,originalObjectiveLimit)
#targets.remove(objectiveName)
return result