insilicolynxdqi 1.0.0
Medicinal Chemistry tool for calculating drug suitability parameters of compounds.
License: BSD 3-clause
Keywords: insilicolynxdqi

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
README file for insilicolynxdqi
=============================================================================================================================================================================================

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Change log
=============================================================================================================================================================================================

17th November 2017: First release written by Mark Wenlock.


---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Copyright
=============================================================================================================================================================================================

Copyright 2017 InSilicoLynx Limited
All 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 2.7.6
	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).


---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 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.	


---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 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.


---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 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).


---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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


=============================================================================================================================================================================================
=============================================================================================================================================================================================