Package: insilicolynxdqi
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------README file for insilicolynxdqi=============================================================================================================================================================================================---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Change log=============================================================================================================================================================================================17th November 2017: First release written by Mark Wenlock.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Copyright=============================================================================================================================================================================================Copyright 2017 InSilicoLynx LimitedAll Rights Reserved.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Licence=============================================================================================================================================================================================The insilicolynxdqi software is covered by a BSD 3-clause license that is included in the LICENSE.txt file distributed with this software.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Description=============================================================================================================================================================================================Medicinal Chemistry tool for calculating drug suitability parameters of compounds.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Platform and version=============================================================================================================================================================================================The software named insilicolynxdqi has been tested for compatibility on the following systems:Ubuntu 14.04 LTS system running Python 2.7.6Ubuntu 14.04 LTS system running Python 3.4.3Ubuntu 16.04 LTS system running Python 2.7.12Ubuntu 16.04 LTS system running Python 3.5.2Windows 7 system running Python 3.6.0The software named insilicolynxdqi should be compatible with Python 2.7(.z) and Python 3(.y.z) running on a Linux platform or a Win32 platform (where y and z are the version numbers of thedistribution).---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------To install on a local computer=============================================================================================================================================================================================(1) Save the compressed source distribution file on to a local computer.(2) Installation from the compressed source distribution file using pip:Within a new terminal (Linux) or a new Command Prompt (Win32), change the working directory to the directory containing the compressed source distribution file and type:>>> sudo pip install insilicolynxdqi-x.y.z.tar.gz (Linux)or>>> pip install insilicolynxdqi-x.y.z.zip (Win32)where x, y and z are the version numbers of the distribution.Note, to uninstall:>>> sudo pip uninstall insilicolynxdqi (Linux)or>>> pip uninstall insilicolynxdqi (Win32)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Using insilicolynxdqi within a Python script - generate in-vivo scenarios functionality=============================================================================================================================================================================================The following code is needed for accessing the generate in-vivo scenarios functionality of insilicolynxdqi:from insilicolynxdqi.run.generate_in_vivo_scenarios import GenerateInVivoScenariosgenerateInVivoScenarios = GenerateInVivoScenarios()generateInVivoScenarios.run( args )The possible arguments (i.e., args) for the generateInVivoScenarios.run() function include:dataFile (df):REQUIRED - full file name of the tab-delimited file containing the data set.  The following data column headers are required (note, the "species" text refers to dog, human or rat):namemol_wtcl_in_vivo_plasma_(species)cl_in_vivo_plasma_(species)_unitsv_steady_state_(species)v_steady_state_(species)_unitsFor calculation of free levels the additional data columns are also required:ppb_(species)ppb_(species)_unitsFor calculation based on oral dosing the additional data columns are also required:charge_typepka_a1 (dependent on charge_type)pka_a2 (dependent on charge_type)pka_b1 (dependent on charge_type)pka_b2 (dependent on charge_type)caco2_6p5_humancaco2_6p5_human_unitssolubility_7p4solubility_7p4_unitsspeciesName (sn):Species: d = dog, h = human, r = rat (default = h).method (m):Method: 1 (po 1c total), 2 (po 1c free), 3 (po 2c total), 4 (po 2c free), 5 (iv 2c total), 6 (iv 2c free) (default = 1).errorScenarios (es):Number of error scenarios to consider (default = 0, can not equal 1).errorParameters (ep):Enter the parameter abbreviation for error consideration (in vivo clearance (cl), volume of distribution at steady state (v), Caco2 Papp A to B at pH 6.5 (caco2), aqueoussolubility at pH 7.4 (solubility) and plasma protein binding (ppb)) e.g., cl v caco2 solubility ppb.  (Note, do not add speech marks.)mappingsFile (mf):Full file path of the file containing the column header mappings for the input data set.rmsepFile (rf):Full file path of the file containing the rmsep values for the associated QSAR models.qsarDefaultRmsep (qdr):Assumed RMSEP for a QSAR model without an entry in the rmsep file.  The value reflects the RMSEP between predicted and observed values both on a logarithmic base-10 scale forcl_in_vivo_plasma_(species), v_steady_state_(species), caco2_6p5_human, solubility_7p4 and predicted and observed values both on a logarithmic base-10 percent bound over percentfree scale for ppb_(species) (default = 1.00).  (Note, the species text refers to dog, human or rat.)qsarExperimentalStandardDeviation (qesd):Assumed default experimental standard deviation associated to measured data.  For cl_in_vivo_plasma_(species), v_steady_state_(species), caco2_6p5_human and solubility_7p4 thisvalue reflects a logarithmic base-10 scale, and for ppb_(species) this value reflects a logarithmic base-10 percent bound over percent free scale (default = 0.30).  (Note, thespecies text refers to dog, human or rat.)defaultParameterStandardDeviation (dpsd):Assumed default parameter standard deviation to be used in the absence of a valid compound standard deviation value and/or a valid compound similarity score.  Forcl_in_vivo_plasma_(species), v_steady_state_(species), caco2_6p5_human and solubility_7p4 this value reflects a logarithmic base-10 scale, and for ppb_(species) this value reflectsa logarithmic base-10 percent bound over percent free scale (default = 0.30).  (Note, the species text refers to dog, human or rat.)nameSubstring (ns):The substring appended to the name (followed by an integer) to indicate an error scenario row (default = _#).byPass (bp):Bypass the Python version and platform check: yes or no (default).Output of generateInVivoScenarios.run( args ):dataFileNew:The file path for the new data file generated by the library - permits joining with other functions within one Python script.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Output - generate in-vivo scenarios functionality=============================================================================================================================================================================================A revised text file.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Using insilicolynxdqi within a Python script - perform in-vivo calculations functionality=============================================================================================================================================================================================The following code is needed for accessing the perform in-vivo calculations functionality of insilicolynxdqi:from insilicolynxdqi.run.perform_in_vivo_calculations import PerformInVivoCalculationsperformInVivoCalculations = PerformInVivoCalculations()performInVivoCalculations.run( args )The possible arguments (i.e., args) for the performInVivoCalculations.run() function include:dataFile (df):REQUIRED - full file name of the tab-delimited file containing the data set (i.e., the output data file from insilicolynxdqi_generate_scenarios).  The following data columnheaders are required (note, the "species" text refers to dog, human or rat):namemol_wtcl_in_vivo_plasma_(species)cl_in_vivo_plasma_(species)_qualifiercl_in_vivo_plasma_(species)_unitsv_steady_state_(species)v_steady_state_(species)_qualifierv_steady_state_(species)_unitsFor calculation of free levels the additional data columns are also required:ppb_(species)ppb_(species)_qualifierppb_(species)_unitsFor calculation based on oral dosing the additional data columns are also required:charge_typepka_a1 (dependent on charge_type)pka_a2 (dependent on charge_type)pka_b1 (dependent on charge_type)pka_b2 (dependent on charge_type)caco2_6p5_humancaco2_6p5_human_qualifiercaco2_6p5_human_unitssolubility_7p4solubility_7p4_qualifiersolubility_7p4_unitsspeciesName (sn):Species: d = dog, h = human, r = rat (default = h).method (m):Method: 1 (po 1c total), 2 (po 1c free), 3 (po 2c total), 4 (po 2c free), 5 (iv 2c total), 6 (iv 2c free) (default = 1).doseInterval (di):Dose interval (frequency), units: hours (default = 12.00).simulationLength (sl):Simulation length, units = hours (default = 168.00).compartment (c):Compartment to consider: c = central, p = peripheral, cp = central_peripheral or all (default = c).  (Note, not relevant for methods involving only one compartment.)name (n):Name (of molecule) column header as it appears in the input data set (default = name).upperVcentralToVssRatio (uvr):Upper ratio for the volume of distribution in the central compartment to the volume of distribution at steady state (needs to be a number between 0.00 and less than 1.00)(default = 0.50).vterminalToVssRatioLower (vrl):Terminal volume of distribution to volume of distribution at steady state ratio lower limit (needs to be greater than or equal to 1.01) (default = 1.10).vterminalToVssRatioUpper (vru):Terminal volume of distribution to volume of distribution at steady state ratio upper limit (needs to be less than or equal to 7.00) (default = 2.00).defaultIvDose (did):Default dose to use with iv scenarios only, units: mg kg-1 (default = 1.00).absorptionDelay (ad):Absorption delay to use with po scenarios only, units: hours (default = -1.00 (and hard coded values used: dog = 0.50; human = 1.00; rat = 0.25)).intestinalTransitTime (itt):Intestinal transit time to use with po scenarios only, units: hours (default = -1.00 (and hard coded values used: dog = 2.00; human = 4.00; rat = 1.50)).saveRawDataFiles (srdf):Save raw data files: yes (default) or no.byPass (bp):Bypass the Python version and platform check: yes or no (default).Output of performInVivoCalculations.run( args ):dataFileNew:The file path for the new data file generated by the library - permits joining with the insilicolynxdqi Python library within one Python script.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Output - perform in-vivo calculations functionality=============================================================================================================================================================================================Multiple text files.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Using insilicolynxdqi within a Python script - analyse in-vivo calculations functionality=============================================================================================================================================================================================The following code is needed for accessing the analyse in-vivo calculations functionality of insilicolynxdqi:from insilicolynxdqi.run.analyse_in_vivo_calculations import AnalyseInVivoCalculationsanalyseInVivoCalculations = AnalyseInVivoCalculations()analyseInVivoCalculations.run( args )The possible arguments (i.e., args)  for the analyseInVivoCalculations.run() function include:dataFile (df):REQUIRED - full file name of the tab-delimited file containing the data set (i.e., the output data file from insilicolynxdqi_perform_calculations) (enter file path prefix formultiple scenarios e.g., ../../folder/data_).speciesName (sn):Species: d = dog, h = human, r = rat (default = h).method (m):Method: 1 (po 1c total), 2 (po 1c free), 3 (po 2c total), 4 (po 2c free), 5 (iv 2c total), 6 (iv 2c free) (default = 0, user must specify a method if full file path provided).nameSubstring (ns):The substring appended to the name (followed by an integer) to indicate an error scenario row (default = _#).compartment (c):Compartment to consider: c = central, p = peripheral, cp = central_peripheral or all (default = c).  (Note, not relevant for methods involving only one compartment.)removeOutliers (ro):If the number of available records permits, the number of outliers to remove - to use with po scenarios only.intervalLevelDistribution (ild):If the number of available records permits, the (approximate) two-sided distribution interval level to calculate - accepted range : 70.00 percent to 100.00 percent(default = 80.00 percent).confidenceMeanLevel (cml):If the number of available records permits, the (approximate) two-sided confidence interval of the mean level to calculate - accepted range : 70.00 percent to 99.90 percent(default = 80.00 percent).  (Note, a minimum of four records is required to calculate the confidence intervals of the mean; and where the degrees of freedom is greater than 150the t-critical value is calculated for 150 degrees of freedom.)smiles (s):If applicable, smiles column header as it appears in the input data set (default = smiles).byPass (bp):Bypass the Python version and platform check: yes or no (default).---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Output - analyse in-vivo calculations functionality=============================================================================================================================================================================================Multiple text files.---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Further information=============================================================================================================================================================================================Refer to INSTRUCTIONS_FOR_USE.txt file included in the distribution (../insilicolynxdqi/docs/).---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Help=============================================================================================================================================================================================Email: contact@insilicolynx.com==========================================================================================================================================================================================================================================================================================================================================================================================