insilicolynxdqi 1.0.0

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README file for insilicolynxdqi
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Change log
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17th November 2017: First release written by Mark Wenlock.


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Copyright
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Copyright 2017 InSilicoLynx Limited
All Rights Reserved.


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Licence
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The insilicolynxdqi software is covered by a BSD 3-clause license that is included in the LICENSE.txt file distributed with this software.


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Description
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Medicinal Chemistry tool for calculating drug suitability parameters of compounds.


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Platform and version
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The software named insilicolynxdqi has been tested for compatibility on the following systems:

Ubuntu 14.04 LTS system running Python 2.7.6
Ubuntu 14.04 LTS system running Python 3.4.3
Ubuntu 16.04 LTS system running Python 2.7.12
Ubuntu 16.04 LTS system running Python 3.5.2
Windows 7 system running Python 3.6.0

The 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 the
distribution).


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To install on a local computer
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(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)


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Using insilicolynxdqi within a Python script - generate in-vivo scenarios functionality
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The following code is needed for accessing the generate in-vivo scenarios functionality of insilicolynxdqi:

from insilicolynxdqi.run.generate_in_vivo_scenarios import GenerateInVivoScenarios
generateInVivoScenarios = 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):

name
mol_wt
cl_in_vivo_plasma_(species)
cl_in_vivo_plasma_(species)_units
v_steady_state_(species)
v_steady_state_(species)_units

For calculation of free levels the additional data columns are also required:

ppb_(species)
ppb_(species)_units

For calculation based on oral dosing the additional data columns are also required:

charge_type
pka_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_human
caco2_6p5_human_units
solubility_7p4
solubility_7p4_units

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 = 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), aqueous
solubility 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 for
cl_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 percent
free 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 this
value 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, the
species 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. For
cl_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 reflects
a 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.


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Output - generate in-vivo scenarios functionality
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A revised text file.


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Using insilicolynxdqi within a Python script - perform in-vivo calculations functionality
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The following code is needed for accessing the perform in-vivo calculations functionality of insilicolynxdqi:

from insilicolynxdqi.run.perform_in_vivo_calculations import PerformInVivoCalculations
performInVivoCalculations = 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 column
headers are required (note, the "species" text refers to dog, human or rat):

name
mol_wt
cl_in_vivo_plasma_(species)
cl_in_vivo_plasma_(species)_qualifier
cl_in_vivo_plasma_(species)_units
v_steady_state_(species)
v_steady_state_(species)_qualifier
v_steady_state_(species)_units

For calculation of free levels the additional data columns are also required:

ppb_(species)
ppb_(species)_qualifier
ppb_(species)_units

For calculation based on oral dosing the additional data columns are also required:

charge_type
pka_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_human
caco2_6p5_human_qualifier
caco2_6p5_human_units
solubility_7p4
solubility_7p4_qualifier
solubility_7p4_units

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 = 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.


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Output - perform in-vivo calculations functionality
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Multiple text files.


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Using insilicolynxdqi within a Python script - analyse in-vivo calculations functionality
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The following code is needed for accessing the analyse in-vivo calculations functionality of insilicolynxdqi:

from insilicolynxdqi.run.analyse_in_vivo_calculations import AnalyseInVivoCalculations
analyseInVivoCalculations = 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 for
multiple 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 150
the 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).


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Output - analyse in-vivo calculations functionality
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Multiple text files.


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Further information
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Refer to INSTRUCTIONS_FOR_USE.txt file included in the distribution (../insilicolynxdqi/docs/).


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Help
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Email: contact@insilicolynx.com


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