toxtree

                              Toxtree README

                       (last revision - 22 Mar 2015)

This is the README file  for the Toxtree installer distribution.  If you're
reading this,  you've probably  just run   our installer  and installed the
Toxtree application on your system.

The present README file could be also accessed at "Start -> All Programs ->
Ideaconsult -> Toxtree-vX.YZ -> README").

CONTENTS

* Introduction
* System Requirements & Installation
* Release Notes
* Bug Reports and Feedback
* Toxtree Documentation
* Redistribution
* Change Log
* To Do

INTRODUCTION

Toxtree  is  a  full-featured   and  flexible  user-friendly  open   source
application, which is able to estimate toxic hazard by applying a  decision
tree approach. Currently it includes the following plugins:

- Cramer rules (Cramer G. M., R.  A. Ford, R. L. Hall, Estimation of  Toxic
Hazard - A  Decision Tree Approach,  J. Cosmet. Toxicol.,  Vol.16,  pp. 255
-276, Pergamon Press, 1978);

- Verhaar scheme for predicting toxicity mode of actions (Verhaar HJM,  van
Leeuwen CJ and Hermens JLM (1992) Classifying environmental pollutants.  1.
Structure-activity  relationships  for  prediction  of  aquatic   toxicity.
Chemosphere 25, 471-491);

- A decision tree for  estimating skin irritation and corrosion  potential,
based on rules published in �The Skin Irritation Corrosion Rules Estimation
Tool  (SICRET),  John  D. Walker,  Ingrid  Gerner,  Etje Hulzebos,  Kerstin
Schlegel, QSAR Comb. Sci. 2005, 24, pp. 378-384�;

- A decision  tree for estimating  eye irritation and  corrosion potential,
based on rules published in �Assessment of the eye irritating properties of
chemicals by applying alternatives to  the Draize rabbit eye test:  the use
of  QSARs and  in vitro  tests for  the classification  of eye  irritation,
Ingrid  Gerner,  Manfred  Liebsch   &  Horst  Spielmann,  Alternatives   to
Laboratory Animals, 2005, 33, pp. 215-237�;

- A decision tree for estimating carcinogenicity and mutagenicity, based on
the rules  published in  the document:  �The Benigni  / Bossa  rulebase for
mutagenicity and carcinogenicity � a module of Toxtree�, by R. Benigni,  C.
Bossa, N. Jeliazkova, T. Netzeva, and A. Worth. European Commission  report
EUR 23241 EN;

- START (Structural  Alerts for Reactivity  in Toxtree) biodegradation  and
persistence plug-in  is based  on a  compilation of  structural alerts  for
environmental persistence and biodegradability. These structural alerts are
molecular functional groups or substructures that are known to be linked to
the  environmental  persistence  or  biodegradability  of  chemicals.   The
rulebase utilizes the structural alerts  in logical decision trees. If  one
or more the  structural alerts embedded  in the molecular  structure of the
chemical  are recognized,  the system  flags the  potential persistence  or
biodegradability of the chemical. Installation and user manuals  available;

- Structure Alerts for the in vivo micronucleus assay in rodents, based  on
the rules, published in the document �Development of structural alerts  for
the in vivo  micronucleus assay in  rodents�, by Romualdo  Benigni, Cecilia
Bossa, Olga Tcheremenskaia and Andrew Worth, European Commission report EUR
23844 EN;

- Cramer  rules with  extensions: This  plug-in is  a copy  of the original
plug-in, plus minor extensions. Like the Cramer plug-in, this plug-in works
by assigning compounds to Class I, II, or III, according to the rules  from
Cramer, and some extra ones. Several compounds were classified by Munro  in
1996 as Class I or Class  II compounds according to the Cramer  rules, even
though Munro reported low NOEL values upon oral administration  (indicating
relatively high toxicity). To overcome such misclassifications, five  rules
have been introduced to capture the possible toxicity of  these  compounds;

- Structure Alerts  for identification of  Michael Acceptors: This  plug-in
contains structural alerts, able to identify Michael Acceptors, as  defined
in 	T. Wayne Schultz, Jason W. Yarbrough, Robert S. Hunter, Aynur O. Aptula
(2007) Verification  of the  Structural Alerts for Michael Acceptors. Chem.
Res. Toxicol. 20, 1359�1363;

-  Skin  sensitization alerts,  as  per Enoch  SJ,  Madden JC,  Cronin  MT,
Identification of mechanisms of toxic action for skin sensitisation using a
SMARTS pattern based approach, SAR QSAR Environ Res. 2008; 19(5-6):555-78; 

-  SMARTCyp  - Cytochrome  P450  - Mediated  Metabolism,  implementation of
Patrik Rydberg, David E. Gloriam, Jed Zaretzki, Curt Breneman, Lars  Olsen,
SMARTCyp:  A  2D Method  for  Prediction of  Cytochrome  P450-Mediated Drug
Metabolism, ACS Med. Chem. Lett., 2010, 1 (3), pp 96�100;

-  Kroes TTC  decision tree  - Kroes,  R., Renwick,  A.G., Cheeseman,  M., 
Kleiner, J., Mangelsdorf, I., Piersma, A., Schilter, B., Schlatter, J., van
Schothorst, F., Vos, J.G.,  Wurtzen, G. (2004). Structure  based thresholds
of  toxicological concern  (TTC): guidance  for application  to substances 
present at low levels in the diet. Food Chem. Toxicol. 42, 65�83;

- Modified Verhaar scheme for  predicting toxicity mode of actions  - rules
reordered, according to S.J. Enoch, M. Hewitt, M.T.D. Cronin, S. Azam, J.C.
Madden,  Classification  of  chemicals according  to  mechanism  of aquatic
toxicity: An  evaluation of  the implementation  of the  Verhaar scheme  in
Toxtree, Chemosphere 73 (2008) 243-248;

-  Structural  Alerts  for Functional  Group  Identification  ISSFUNC (DOI:
10.2788/33281,  Catalogue   Number:  LB-NA-24871-EN-N),   Benigni  R.,   O.
Tcheremenskaia, and A.  Worth, Computational Characterisation  of Chemicals
and  Datasets  in  Terms  of Organic  Functional  Groups  -  a New  Toxtree
Rulebase;

- Protein binding - S.  J. Enoch, C. M. Ellison,  T. W. Schultz & M.  T. D.
Cronin,  A  review  of the  electrophilic  reaction  chemistry involved  in
covalent  protein  binding  relevant  to  toxicity,  Critical  Reviews   in
Toxicology, 2011, 1-20;

- Structural alerts associated with covalent DNA binding. - S. J. Enoch and
M. T. D. Cronin, A review of the electrophilic reaction chemistry  involved
in covalent DNA binding, Critical Reviews in Toxicology,2010;40(8):728-748;

-  A  decision  tree  for estimating  in  vitro  mutagenicity  (Ames test).
Benigni,   R.,  Bossa   C.,  Tcheremenskaia   O.  (2013)   In  vitro   cell
transformation  assays  for   an  integrated,  alternative   assessment  of
carcinogenicity: a data-based analysis. Mutagenesis 2013;28(1):107-16.

Toxtree could  be applied  to datasets from various compatible file  types.
User-defined  molecular  structures  are also  supported  -  they could  be
entered by  SMILES, or by using the built-in  2D structure diagram  editor.

The  Toxtree  application  is suitable  for a  standalone PC.  It has  been
designed with  flexible capabilities  for future  extensions in  mind (e.g.
other classification schemes that could be developed at a future date). New
decision trees with arbitrary rules can be built with the help of graphical
user interface or by developing new plug-ins.

SYSTEM REQUIREMENTS & INSTALLATION

Toxtree requires Java(TM)  2 Runtime Environment,  Standard Edition 1.7  or
newer on the  target system and  it is platform-independent.  It runs under
any host operating  system, which supports Java(TM) 2 Runtime  Environment,
Standard Edition.

The  Toxtree  application is  distributed  with a  fully  automated offline
installer (Toxtree-vX.Y.Z-setup.exe),  compatible with  recent versions  of
the Microsoft Windows (NT, 2000, XP, 2003, 7, 2008)  operating  system.  In
order  to   install   Toxtree   just  run  the  installer  and  follow  its
instructions. It contains all the required packages, including the Java(TM)
2 Runtime Environment, Standard Edition 1.7 setup.

If the installer does not detect Java(TM) 2 Runtime  Environment,  Standard
Edition 1.7 or  newer on the  target system, it will attempt to install  it
before proceeding with  the Toxtree setup.  In this case,  the user running
the installer SHOULD  HAVE ADMINISTRATIVE PRIVILEGES  on the target  system
(otherwise the Java(TM) 2 Runtime Environment, Standard Edition setup would
be aborted and Toxtree would not be installed).

If the installer detects  Java(TM) 2 Runtime Environment,  Standard Edition
1.7  or  newer  already installed  on the  target system,  it will  proceed
directly with the  Toxtree setup. In  this case, ADMINISTRATIVE  PRIVILEGES
ARE RECOMMENDED BUT NOT NECESSARILY REQUIRED.

When the installer is launched by a user with administrative privileges, it
will create Toxtree  start menu shortcuts  for all the  users registered in
the target system. Otherwise, start menu shortcuts will be created only for
the unprivileged user, who launched the installation.

After a successful installation, Toxtree  could be launched from the  Start
Menu ("Start ->  All Programs ->  Ideaconsult -> Toxtree-vX.Y.Z  -> Toxtree
-vX.Y.Z").

Each version of Toxtree could  be uninstalled either by using  the "Control
Panel  -> Add  or Remove  Programs" or  by  clicking  the "Uninstall"  link
located  in  "Start  -> All  Programs ->  Ideaconsult ->  Toxtree-vX.Y.Z ->
Uninstall-Toxtree-vX.Y.Z". Any  application files  which may  happen to  be
locked  during the  uninstall procedure  would be  deleted after  the  next
reboot  of the  system. Java(TM)  2 Runtime  Environment, Standard  Edition
would not be uninstalled by the Toxtree uninstaller. If needed, it could be
uninstalled via its own entry in "Control Panel -> Add or Remove Programs".

RELEASE NOTES

Toxtree-v2.6.13 is a stable release with new features and bug fixes.

BUG REPORTS AND FEEDBACK

You should send any comments, inquiries, bug reports, feature requests  and
other suggestions to Nina Jeliazkova <[e-mail]>

TOXTREE DOCUMENTATION

The  complete Toxtree  documentation is  located in  the "doc"  application
subfolder.

REDISTRIBUTION

Toxtree  is  distributed  under   the  GNU  General  Public   License  (see
LICENSE.txt). It is freely distributable.

CHANGE LOG

* Toxtree-v2.6.13 (build date 22 Mar 2015):

- updated to ambit-2.7.3;

- updated to Open Parser for Systematic IUPAC Nomenclature (OPSIN) 1.6.0;

- fixed remote query issue;

- added command line options for running Toxtree headless;

- included jre-7u75-windows-i586.exe in Windows installer;

- fixed Java version detection issue in the installer;

- updated manuals and README;

* Toxtree-v2.6.6 (build date 15 Jun 2014):

- updated to Open Parser for Systematic IUPAC Nomenclature (OPSIN) 1.5.0;

- updated to ambit-2.5.6;

- fixed plugin loading issue (was manifested only on Linux platforms);

- included jre-7u60-windows-i586.exe in Windows installer;

- updated README;

* Toxtree-v2.6.0 (build date 10 Jul 2013):

- updated to cdk 1.4.11;

- updated to Open Parser for Systematic IUPAC Nomenclature (OPSIN) 1.4.0;

- updated to ambit-2.4.12;

- renamed  the  Skin  sensitisation  alerts  plugin  to  Skin sensitisation
 reactivity domains;

- added In vitro mutagenicity (Ames test) alerts plugin (developed by
ISS);

- added Structural alerts associated with covalent DNA binding plugin;

- fixed bug causing instability under Java 7;

- fixed bug in the Decision rules editor;

- fixed bug affecting substituents recognition in Carcinogenicity plugin;

- included jre-7u25-windows-i586.exe in Windows installer;

- updated manuals and README;

* Toxtree-v2.5.4 (build date 02 Apr 2012):

- added new plugin "Protein binding",  which implements S. J. Enoch, C.  M.
Ellison, T. W.  Schultz & M.  T. D. Cronin,  A review of  the electrophilic
reaction  chemistry  involved  in  covalent  protein  binding  relevant  to
toxicity, Critical Reviews in Toxicology, 2011, 1-20.

- updated CDK to v1.4.8;

- updated JChemPaint to v3.3.0;

- updated to jre-6u31-windows-i586;

- fixed bug 3493804 (Different results between 2.5.0 and earlier versions);

- fixed bug 3493431 (Cramer Rule 20 behaviour);

- fixed bug 3492853 (Some compounds not found in bodymol.sdf);

- fixed bug 3491753 (Non serializable exception in CYP450 module);

- fixed bug 3488950 (Cramer2 Q42 rule);

- fixed bug 3472325 (Micronucleus plugin SA34 rule);

- fixed bug 3431053 (Incorrect structure of protoheme in bodymol.sdf);

- fixed bug 3396489 (Name of the "skin sensitization alerts" plugin changed);

- fixed bug 3089700 (Cramer2 rule 4);

- fixed bug 3089699 (Cramer2 rule 40);

- updated installation and user manual;

- updated README.

* Toxtree-v2.5.1 (build date 03 Feb 2012):

- corrected Schiff base SMARTS;

- fixed ionic bonds matching;

- fixed explanation for RuleAliphaticWithSomeFuncGroups in Cramer rules and
Extended Cramer rules;

- fixed recognition of  carbonyl in amide group,  affecting Q18 and Q20  of
Cramer rules;

- included jre-6u30-windows-i586.exe in Windows installer;

- updated manuals and README;

* Toxtree-v2.5.0 (build date 05 Aug 2011):

- updated to cdk 1.3.8;

- updated to ambit-2.4.2;

- OpenBabel  is no  longer included  in the  distribution; in  order to use
OpenBabel (optionally)  from within  Toxtree, install  OpenBabel separately
and set the OBABEL_HOME environment  variable to point to the  folder where
OpenBabel is installed;

- added metadata for all plugins (explanation, references, vendor, links to
datasets);

- improved display of decision tree details;

- improved help menus (About / Files info / Help);

- enabled  CAS  &  EINECS  lookup  in  remote  OpenTox  service;  this  new
functionality  is  disabled  by  default  --  check  "Method/Decision  tree
option/Remote Query" menu to enable it;

- added two  new plug-ins: Modified  Verhaar scheme, and  Structural Alerts
for Functional Group Identification (ISSFUNC);

- fixed  Cramer rules  Q2 (NC#N  recognised as  functional group associated
with enhanced toxicity);

- fixed Cramer rules Q2 (secondary amine highlight);

- fixed Benigni / Bossa rulebase SA31b (biphenyls recognition);

- fixed Benigni / Bossa rulebase SA30 (coumarins recognition);

- fixed Benigni / Bossa rulebase rule (QSAR6,8 applicability domain);

- improved  implementation of  Verhaar scheme  plugin; validated  against a
published dataset;

- SMARTCyp  plug-in  -  added  metabolite  generation,  based  on  Site  of
Metabolism, calculated by SMARTCyp and ambit-SMIRKS package.

- included jre-6u26-windows-i586.exe in Windows installer;

- updated manuals and README;

* Toxtree-v2.2.0 (build date 25 Oct 2010):

- updated to cdk 1.3.67 (= cdk 1.3.6 + jni-inchi 0.7 );

- updated to jchempaint-3.1.3;

- fixed not working Edit/Preferences;

- removed valency labels that were appearing in JChemPaint by default;

- fixed rendering of disconnected structures (e.g. salts);

- fixed Cramer rule Q3 - S in aromatic ring is now recognized as divalent;

- included jre-6u22-windows-i586.exe in Windows installer;

- updated manuals and README.

* Toxtree-v2.1.1 (build date 07 Oct 2010):

- upgraded to Java 1.6;

- included jre-6u21-windows-i586.exe in Windows installer;

- upgraded to OpenBabel v2.2.3;

- fixed SMILES parsing (OpenBabel v2.2.3);

- enabled InChI-to-structure conversion based on jni-inchi-0.7-std;

- enabled name-to-structure conversion based on OPSIN v0.8.0;

- fixed outcome from QSAR8;

- values "true" and "false" in input file will be parsed into 1 or 0;

- fixed batch processing "Non serializable exception" for micronucleus  and
skin sensitiation plugins;

- added check for phosphates in Q4 of Cramer Extended rules;

- updated manuals and README.

* Toxtree-v2.1.0 (build date 30 Jun 2010):

- added highlighting of structural alerts;

- upgraded Toxtree to JChemPaint 3.0.1 and CDK 1.3.3;

- added 3  new plug-ins (Skin  sensitization alerts, SMARTCyp  - Cytochrome
P450 - Mediated Metabolism & Kroes TTC  decision tree);

- implemented several bug fixes;

- updated manuals and README.

* Toxtree-v1.60 (build date 15 Jul 2009):

- added Cramer rules with extensions plugin and updated bodymol.sdf;

- added  Structure Alerts  for the  in vivo  micronucleus assay  in rodents
plugin;

- added START biodegradation and persistence plugin;

- added tructural Alerts for identification of Michael Acceptors plugin;

- Skin irritation plugin: fixed bugs in rules Q52 and Q53;

- Cramer rules plugin: fixed bugs in Q8 and Q21;

- Begnini/Bossa rulebase  plugin: fixed issue  when results for  structural
alerts (e.g. SA10) are not displayed if the outcome is YES;

-  Begnini/Bossa  rulebase  plugin:  QSAR8  question  rephrased,  to  avoid
confusion;

- fixed issue when editing an  example in the decision tree editor  was not
working;

- introduced TOXTREE environment variable, which should be set to point  to
the Toxtree-<version>.jar  and helps  locating SDF  files and  plugins when
Toxtree is used by third party software;

- fixed issue when after creating a new tree it could not be saved;

• OpenBabel updated to v2.2.1 (build March 2, 2009);

  • updated documentation;

  • updated README;

  • Toxtree-v1.51 (build date 26 Jun 2008):

  • fixed property checking rules bug;

  • updated README;

  • Toxtree-v1.50 (build date 30 May 2008):

  • added support for eye irritation/corrosion prediction;

  • updated user manual;

  • updated README;

  • Toxtree-v1.40 (build date 24 Mar 2008):

  • improved descriptor calculations (I(An),I(BiBr));

  • updated QSAR6, QSAR8, QSAR13;

  • new decision tree layout based on prefuse library - can be exported as .png, .bmp, .jpg or .gif;

  • new decision tree export options - .html, .pdf or .txt;

  • user preference options (persistent accross application instances);

  • updated user manual;

  • updated README;

  • Toxtree-v1.36 (build date 17 Feb 2008):

  • improved partial molar refractivity, Sterimol and Idist descriptor calculation;

  • updated README;

  • Toxtree-v1.35 (build date 3 Feb 2008):

  • updated the structural alerts for predicting carcinogenicity and mutagenicity;

  • updated descriptor computations;

  • updated README;

  • Toxtree-v1.34 (build date 20 Jan 2008):

  • updated CDK library;

  • updated the structural alerts for predicting carcinogenicity and mutagenicity;

  • updated descriptor computations;

  • updated README;

  • Toxtree-v1.33 (build date 6 Jan 2008):

  • updated to CDK 1.1 release;

  • updated the structural alerts for predicting carcinogenicity and mutagenicity to take into account overlaps;

  • updated README;

  • Toxtree-v1.32 (build date 26 Sep 2007):

  • support for assigning multiple labels;

  • improved implementation of structural alerts for the decision tree for predicting carcinogenicity and mutagenicity;

  • MOPAC call bug fix;

  • updated README;

  • Toxtree-v1.31 (build date 21 Aug 2007):

  • initial implementation of a decision tree for predicting carcinogenicity and mutagenicity - 35 structural alerts and 3 linear discriminant rules, making use of 11 descriptors;

  • new descriptors implemented:

    +Partial Molar Refractivity of substituents, according to a lookup table

    +Sterimol L & B5 descriptors, according to a lookup table

    +Molar Refractivity (uses Joelib implementation of "S. A. Wildman and G. M. Crippen, Prediction of Physicochemical Parameters by Atomic Contributions, J. Chem. Inf. Comput. Sci., 39, 868-873, 1999")"

    +Descriptors for structure presence of aniline, NO2 & bridged biphenyls

    +EHOMO, ELUMO and other electronic descriptors calculated by launching MOPAC 7.1 (http://openmopac.net) with fixed options (AM1)

  • added substituents.sdf file (substituents lookup table);

  • added helper directory, containing MOPAC_7.1.exe;

  • updated README;

  • Toxtree-v1.30 (build date 19 Jun 2007):

  • updated to CDK 1.0 release;

  • updated to jre-1_5_0_12;

  • prototype implementation of a decision tree for predicting carcinogenicity and mutagenicity;

  • updated README;

  • Toxtree-v1.20 (build date 11 Mar 2007):

  • added global options for skin irritation rules (in addition to rule specific options);

  • added "Silent" option for skin irritation property rules (the answer of the property rule will always be "No" if a property is missing);

  • improved implementation of Verhaar scheme Class 4;

  • fixed error when writing SMARTS rule to .tree file;

  • updated installation manual;

  • updated user manual;

  • updated README;

  • Toxtree-v1.12 (build date 18 Jan 2007):

  • added new rule type based on SMARTS;

  • redesigned decision tree editor;

  • added Verhaar scheme plugin (Toxicity mode of action prediction);

  • added BfR rules plugin (skin irritation/corrosion prediction);

  • updated CDK library;

  • updated README.

  • Toxtree-v1.00 (build date 23 Oct 2005):

  • added complete application documentation, including installation manual, user manual, updated README, documentation of the source code;

  • improvements of the decision tree editor.

  • Toxtree-v0.05 (build date 14 Oct 2005):

  • user defined decision tree concept introduced;

  • decision trees can be saved to and loaded from a file (a custom ".tree" file type is used);

  • added graphical user interface for building decision trees;

  • the structure diagram editor (JChemPaint) is now launched as a nonmodal dialog. This resolves the issue of some JChemPaint windows being inaccessible if the editor is launched as a modal dialog;

  • after structure is edited in JChemPaint, SMILES is created and other properties are retained;

  • new command line options are introduced:

  java -jar Toxtree.jar -f

  java -jar Toxtree.jar -b

  • improved recognition of carbohydrates;

  • several nucleotides added to bodymol.sdf according to an expert advice;

  • better recognition of some ionic groups (note that [Ca++] is recognised only as [Ca+]. For correct representation use [Ca+2] in SMILES);

  • batch processing can not be started anymore when input and output files are the same;

  • Q11: when a heterocyclic ring substituents are analysed, only heteroatoms in the ring analysed are disregarded (as specified in the Cramer et all,

  1. but not the heteroatoms in other rings. This behaviour is the one of v0.03. In the v0.04 release the behaviour was changed to disregard all heteroatoms, which doesn't follow the specification of Q11 to analyze each ring separately, with the remainder of the structure as substituents of that heteroring;

  • added the application source code in the installers;

  • Toxtree-v0.04 (build date 04 Oct 2005):

  • Q5: better heuristics for carbohydrates;

  • Q6: return "yes" only if the a)- and b)-substituents are present simultaneously;

  • Q9: if it is a lactone from this point on treat the structure as if it were the hydroxy acid;

  • Q11: ketone changed to R-C(=O)-R where R is not (O or H);

  • checked the search path for bodymol.sdf and foodmol.sdf, when the application is run from the installer;

  • checked that compounds are assigned always the highest (most hazardous) class of their constituents/hydrolysis products;

  • optimized searching in foodmol.sdf and bodymol.sdf;

  • updated foodmol.sdf and bodymol.sdf according to an expert advice;

  • added Back/Forward buttons for easier navigation in the history of the SMILES drop down list;

  • made the SMILES entry panel inaccessible for user input, when there is an open file. The name of the file is displayed instead of the SMILES entry panel. If changes are made in the file contents in memory, an asterisk (*) is displayed after the file name. The asterisk is removed after saving the file. Access to the SMILES entry panel is restored after File/New.

  • added keyboard shortcut (hotkey CTRL+SHIFT+T) for application launching;

  • added Start Menu tool tips;

  • minor enhancements of the installers;

  • updated README.

  • Toxtree-v0.03 (build date 30 Sep 2005):

  • included a 2D molecular structure editor based on JChemPaint. It could be accessed via the Compound/Edit menu;

  • processes correctly SDF, CSV and TXT files with empty molecules;

  • fixed incorrect perception of a specific functional groups configuration;

  • bodymol.sdf and foodmol.sdf updated according to an expert advice;

  • minor enhancements of the user interface;

  • updated README.

  • Toxtree-v0.02 (build date 25 Sep 2005):

  • Q1 and Q22: implemented to look up for "normal constituent of the body" and "common component of food" in bodymol.sdf and foodmol.sdf respectively. Only a very limited number of molecules are listed currently in these files. The user can replace these files with his own files, provided the names are the same. The files are expected to be in the same directory as Toxtree.jar (the executable file of the Toxtree application). If the files are not found there, the corresponding rules behave as "NOT IMPLEMENTED" and answer "NO" for every compound;

  • Q4: treat the compound as free acid, amine, unsulphonated or unsulphated compound except for the purposes of Q24 and Q33 (as specified in Q4 of Cramer rules);

  • Q15, Q17, Q29, Q30, Q31: hydrolysis products (if any) are processed separately, as required by these rules. If the products are assigned different classes, the entire compound will be assigned the most hazardous class (i.e. - if one product is of class I and another of class III, the entire compound is considered of class III);

  • ionic representation of compounds is processed correctly now (please, report any exceptions);

  • checked that the following input file types are processed correctly (File/Open):

  CML CSV - comma delimited, has a header; HIN ICHI INCHI MDL MOL MDL SDF MOL2 PDB SMI - each line starts with a SMILES, optional name delimited by single space, no header); TXT - tab delimited; XYZ

  • input/output of CSV and TXT: a column with "SMILES" heading is mandatory in order the structure to be read. All other fields are optional, will be read as molecule properties and displayed as such;

  • all the properties from SDF files are read;

  • output (File/Save): molecules can be written to SDF, CSV or TXT files, together with their Cramer classification data (class & path);

  • decision tree results are written as SDF properties or CSV/TXT columns. The class assignment is stored in a property "toxTree.tree.cramer.CramerRules". The tree path is stored in a property "toxTree.tree.cramer.CramerTreeResult";

  • added a batch processing facility. It allows faster processing without loading simultaneously all the compounds into memory. Please, use batch processing if the file has more than thousand compounds. A batch could be paused, continued after pause or cancelled. Batch configuration (i.e. input/output file and processed records) could be saved in a file, loaded and continued in a later moment, even after the application has been closed and started again later. Batch configuration is saved in a temporary file by default. This file is deleted if the batch completes successfully. If the batch configuration is saved into a user defined file, it will persist even after the batch completes;

  • moved the SMILES entry panel from the left to the top of the application window;

  • history of entered SMILES' is kept in a drop down list;

  • the left panel now displays all the properties defined for a molecule (not only CAS, SMILES and NAME as in the previous version). The properties are read from a file (e.g. CSV columns, SDF fields) or set when decision tree estimation is performed. When the compound is created from SMILES (using the SMILES entry panel at the top) the property SMILES is set as well as a remark "Created from SMILES";

  • compounds, consisting of more than one disconnected moiety, are now displayed;

  • removed the "Explain" button on the right panel, since the result is automatically explained on estimation. A check box "Verbose explanation" is added instead. It affects the way results are explained;

  • since there can be more than one hydrolysis product, the results for each product are displayed in brackets ();

  • the application can be configured to output a lot of information on its behaviour. This could be useful for debugging as well as for detailed study of decision tree results. In order to start the application and output debugging messages to the console, type on a command line the following command:

  java -DtoxTree.debugging=true -jar toxTree.jar

  To store log in a file use:

  java -DtoxTree.debugging=true -jar toxTree.jar > toxTree.log

  • minor enhancements of the installer;

  • updated README.

  • Toxtree-v0.01 (build date 24 Aug 2005):

  • first public beta-release of the Toxtree application.

TO DO

* this section is empty.

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Developed (2013) by Ideaconsult Ltd., 4 Angel Kanchev St., 1000 Sofia, Bulgaria