Setconstraints

AAStorage[source]

This script defines amino acids that can be stored by one or more organs

individualizedLabReport(model, IndividualParameters, InputData, optionCardiacOutput)[source]

Compute personalised physiological parameters and constraints for a whole-body metabolic model from provided individual laboratory input data

USAGE:

[modelPersonalized, IndividualParametersNew] = individualizedLabReport (model, IndividualParameters, InputData, optionCardiacOutput)

INPUTS:

  • model – whole-body metabolic model structure

  • IndividualParameters – structure of individual physiological parameters (for example generated by standardPhysiolDefaultParameters), read and updated with the fields:

    • .ID - subject identifier

    • .sex - biological sex (‘male’ or ‘female’)

    • .age - age in years

    • .bodyWeight - body weight in kg

    • .Height - height in cm

    • .Hematocrit - hematocrit as a fraction

    • .HeartRate - heart rate in beats per minute

    • .VO2 - oxygen consumption rate used for cardiac output estimation

    • .MConUrCreatinineMin - minimum urinary creatinine concentration (mg/dL)

    • .MConUrCreatinineMax - maximum urinary creatinine concentration (mg/dL)

    • .BloodVolume - estimated blood volume in ml (Nadler equation)

    • .StrokeVolume - stroke volume in ml/beat

    • .CardiacOutput - cardiac output in ml/min

    • .CardiacOutput_Note - text describing how the cardiac output was derived

    • .Feasible - cell array of feasibility messages after each personalisation step

    • .BloodMetabolites - personalised blood metabolite concentration bounds

    • .UrineMetabolites - personalised urine metabolite concentration bounds

    • .CerebrospinalFluid - personalised CSF metabolite concentration bounds

  • InputData – cell array with one row per measurement and columns {parameter/metabolite name, unit, value}; the metabolite compartment is indicated by a [bc], [u] or [csf] suffix on the name

OPTIONAL INPUT:

optionCardiacOutput – method used to estimate cardiac output (default 1):

  • 1 - CardiacOutput = HeartRate * StrokeVolume

  • 2 - cardiac output set equal to blood volume

  • 0 - polynomial estimate from body weight

  • 3 - Fick principle from VO2

  • 4 - Fick principle with VO2 from body surface area

  • -1 - skip adjustment of cardiac output

OUTPUTS:

  • modelPersonalized – whole-body metabolic model with personalised physiological and metabolomic constraints applied (its .osenseStr is set to ‘max’)

  • IndividualParametersNew – updated individual parameters, i.e. the input IndividualParameters after personalisation

physiologicalConstraintsHMDBbased(model, IndividualParameters, ExclList, Type, InputData, Biofluid, setDefault, ExclMet, ExclMetAbbr)[source]

Apply physiologically-derived concentration constraints to a whole-body metabolic model. Metabolite concentrations are given in uM and organ weights in g. Reaction-specific constraints derived from the literature are applied at the end of the function

USAGE:

modelConstraint = physiologicalConstraintsHMDBbased (model, IndividualParameters, ExclList, Type, InputData, Biofluid, setDefault, ExclMet, ExclMetAbbr)

INPUTS:

  • model – whole-body metabolic model structure with fields:

    • .rxns - n x 1 reaction identifiers

    • .mets - m x 1 metabolite identifiers

    • .S - m x n stoichiometric matrix

    • .lb - n x 1 lower bounds (updated)

    • .ub - n x 1 upper bounds (updated)

  • IndividualParameters – structure of physiological parameters (as generated by standardPhysiolDefaultParameters) with fields:

    • .sex - biological sex (‘male’ or ‘female’), selecting the blood-flow column

    • .CardiacOutput - cardiac output in ml/min

    • .Hematocrit - hematocrit as a fraction

    • .GlomerularFiltrationRate - glomerular filtration rate in ml/min

    • .CSFFlowRate - cerebrospinal fluid flow rate

    • .CSFBloodFlowRate - cerebrospinal fluid to blood flow rate

    • .UrFlowRate - urine flow rate

    • .bodyWeight - body weight in kg

    • .MConDefaultBc - default maximum metabolite concentration in blood (uM)

    • .MConDefaultCSF - default maximum metabolite concentration in CSF (uM)

    • .MConDefaultUrMax - default maximum metabolite concentration in urine (uM)

    • .MConDefaultUrMin - default minimum metabolite concentration in urine (uM)

    • .MConUrCreatinineMax - maximum urinary creatinine concentration (mg/dL)

    • .MConUrCreatinineMin - minimum urinary creatinine concentration (mg/dL)

    • .bloodFlowData - cell array of organ-specific blood-flow percentages

    • .bloodFlowPercCol - column indices in bloodFlowData for the male/female percentages

    • .bloodFlowOrganCol - column index in bloodFlowData holding the organ names

OPTIONAL INPUTS:

  • ExclList – list of reaction identifiers that should not receive an updated bound

  • Type – input type, either ‘HMDB’ (default, concentrations are read from the bundled HMDB text files) or ‘direct’ (concentrations are taken from InputData)

  • InputData – for Type ‘direct’, a cell array whose first column holds VMH metabolite identifiers, second column the minimum concentrations and third column the maximum concentrations

  • Biofluid – biofluid to constrain: ‘all’ (default for HMDB) or, for direct input, one of ‘bc’, ‘u’ or ‘csf’

  • setDefault – if true (default 1) apply default concentration ranges to metabolites without input data

  • ExclMet – if 1, exclude the metabolites listed in ExclMetAbbr from constraint application (default 0)

  • ExclMetAbbr – list of metabolite identifiers to exclude when ExclMet is 1

OUTPUT:

modelConstraint – whole-body metabolic model with the physiological uptake, secretion and excretion constraints applied (updated .lb and .ub)

physiologicalConstraintsHMDBbased_old(model, IndividualParameters, ExclList, Type, InputData, Biofluid, setDefault)[source]

Apply physiologically-derived concentration constraints to a whole-body metabolic model (legacy version). Metabolite concentrations are given in uM and organ weights in g

USAGE:

modelConstraint = physiologicalConstraintsHMDBbased (model, IndividualParameters, ExclList, Type, InputData, Biofluid, setDefault)

INPUTS:

  • model – whole-body metabolic model structure

  • IndividualParameters – structure of physiological parameters (as generated by standardPhysiolDefaultParameters) with fields:

    • .gender - subject gender

    • .sex - biological sex (‘male’ or ‘female’), selecting the blood-flow column

    • .CardiacOutput - cardiac output in ml/min

    • .Hematocrit - hematocrit as a fraction

    • .CSFFlowRate - cerebrospinal fluid flow rate

    • .CSFBloodFlowRate - cerebrospinal fluid to blood flow rate

    • .UrFlowRate - urine flow rate

    • .bodyWeight - body weight in kg

    • .MConDefaultBc - default maximum metabolite concentration in blood (uM)

    • .MConDefaultCSF - default maximum metabolite concentration in CSF (uM)

    • .MConDefaultUrMax - default maximum metabolite concentration in urine (uM)

    • .MConDefaultUrMin - default minimum metabolite concentration in urine (uM)

    • .MConUrCreatinineMax - maximum urinary creatinine concentration (mg/dL)

    • .MConUrCreatinineMin - minimum urinary creatinine concentration (mg/dL)

    • .bloodFlowData - cell array of organ-specific blood-flow percentages

    • .bloodFlowPercCol - column indices in bloodFlowData for the male/female percentages

    • .bloodFlowOrganCol - column index in bloodFlowData holding the organ names

OPTIONAL INPUTS:

  • ExclList – list of reaction identifiers to be excluded from receiving updated bounds

  • Type – input type, either ‘xlsx’ (default) or ‘direct’; if ‘direct’, InputData must be provided

  • InputData – for Type ‘direct’, a cell array whose first column holds VMH metabolite identifiers and further columns the associated concentration data points

  • Biofluid – biofluid to constrain: ‘all’ (default) or, for direct input, one of ‘bc’, ‘u’ or ‘csf’

  • setDefault – if true, apply default concentration ranges to metabolites without input data

OUTPUT:

modelConstraint – whole-body metabolic model with the physiological constraints applied to its reaction bounds

readInDietFromVMH(fileNameDiet)[source]

Read in a diet that has been created and downloaded from the VMH nutrition tool (https://www.vmh.life/#nutrition) and convert it into the format used by the whole-body metabolic model

USAGE:

[DietFormulation] = readInDietFromVMH (fileNameDiet)

INPUT:

fileNameDiet – cell whose first entry is the name of the diet spreadsheet to read; the Excel file fileNameDiet{1} provides the flux values (column 1) and the reaction names (column 6)

OUTPUT:

DietFormulation – d x 2 cell array defining the diet, with the diet exchange reaction identifiers (Diet_EX_…[d]) in the first column and their flux values in the second

setDietConstraints(model, Diet, factor)[source]

Set diet constraints on the bounds of the diet uptake reactions of a whole-body metabolic model. Uptake bounds are given in mmol/day/person

USAGE:

model = setDietConstraints (model, Diet, factor)

INPUT:

model – whole-body metabolic model structure with fields:

  • .rxns - n x 1 reaction identifiers, used to locate the Diet_EX_… uptake reactions

  • .lb - n x 1 lower bounds (updated with the diet uptake rates)

  • .ub - n x 1 upper bounds (updated with the diet uptake rates)

OPTIONAL INPUTS:

  • Diet – diet specification, either the name of a predefined diet (‘EUAverageDiet’ (default), ‘HighFiberDiet’, ‘HighProteinDiet’, ‘UnhealthyDiet’ or ‘VegetarianDiet’) or a diet cell array whose first column holds diet exchange reaction identifiers and whose second column holds the corresponding flux values

  • factor – scalar between 0 and 1 scaling the applied diet; default is 1 (i.e. 100% of the provided diet)

OUTPUT:

model – whole-body metabolic model with the diet uptake constraints applied, updating the fields:

  • .lb - lower bounds of the diet exchange reactions

  • .ub - upper bounds of the diet exchange reactions

  • .SetupInfo - structure recording the setup; the applied diet is stored in .SetupInfo.DietComposition

setFeedingFastingConstraints(model, feedingStatus, fastingValue, storageValue)[source]

Set feeding or fasting constraints on a whole-body metabolic model. Under feeding the organ storage (sink) reactions are enabled to store metabolites (lower bound 0, positive upper bound) and diet uptake is opened; under fasting the storage reactions are reversed to release stored metabolites (negative lower bound, upper bound 0) and diet uptake is closed

USAGE:

model = setFeedingFastingConstraints (model, feedingStatus, fastingValue, storageValue)

INPUT:

  • model – whole-body metabolic model structure with fields:

    • .rxns - n x 1 reaction identifiers, used to locate the sink, demand and diet exchange reactions

    • .lb - n x 1 lower bounds (updated)

    • .ub - n x 1 upper bounds (updated)

    • .Microbiota - optional flag vector marking microbial reactions, checked to leave microbe sinks untouched

    • .rxnGeneMat - optional reaction-gene mapping, removed if present

  • feedingStatus – ‘feeding’ to open diet uptake (using fastingValue) and turn organ storage on, or ‘fasting’ to close diet uptake and turn organ storage release on

OPTIONAL INPUTS:

  • fastingValue – lower bound applied to diet exchange and storage release reactions; default is -10

  • storageValue – upper bound applied to organ storage reactions during feeding; default is 10

OUTPUT:

model – whole-body metabolic model with the feeding/fasting constraints applied, updating the fields:

  • .lb - lower bounds of the affected reactions

  • .ub - upper bounds of the affected reactions

  • .SetupInfo - structure recording the setup; the feeding status is stored in .SetupInfo.FeedingStatus

standardPhysiolDefaultParameters[source]

This script creates the IndividualParameters structure which contains standard physiological default parameters for the reference man or woman.

Ines Thiele 2016-2019