                                  Toxtree README

                           (last revision - 04 May 2018)

    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, 13591363;

    -  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 96100;

    -  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, 6583;

    - 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.

    - Revised Cramer Decision Tree: An updated/revised Cramer decision tree for
    the  allocation  of  substances  of known structure into class I, II or III
    based on potential oral toxicity. Available since ToxTree 3.1.0.  Developed
    by IdeaConsult Ltd., (Sofia, Bulgaria)  for  the International Organization
    of the Flavor Industry (IOFI) and the  Flavor and Manufacturers Association
    (FEMA).

    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)  Runtime Environment,  Standard Edition  1.8 or
    newer on the  target system and  it is platform-independent.  It runs under
    any host  operating system,  which supports  Java(TM) 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  operating system (Vista,  7, 8, Server  2008, Server
    2012). In order to  install Toxtree just run  the installer and follow  its
    instructions. It contains all the required packages, including the Java(TM)
    Runtime Environment, Standard Edition 1.8 setup.

    If the  installer does  not detect  Java(TM) Runtime  Environment, Standard
    Edition 1.8 (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) Runtime  Environment, Standard Edition setup  would
    be aborted and Toxtree would not be installed).

    If the installer detects Java(TM) Runtime Environment, Standard Edition 1.8
    (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) 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-v3.1.0.1851 is a stable version 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 <jeliazkova.nina@gmail.com>

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-v3.1.0 (build date 04 May 2018):

    - cramer3 bug fixes;

    - updated README;

    * Toxtree-v3.1.0 (build date 30 Apr 2018):

    - new plugin {{{./cramer3.html}<<Revised Cramer Decision Tree>>}};

    - updated to {{{http://ambit.sf.net}AMBIT-3.2.0}};

    - updated to {{{http://cdk.sf.net}cdk 1.5.13}};

    - bug fixes;

    - built with JDK 8;

    - updated installer;

    - included jre-8u171-windows-i586.exe in Windows installer;

    - updated README;

    * Toxtree-v3.0.2 (build date 06 Jul 2017):

    - multiple bug fixes in Revised Cramer Decision Tree module;

    - included jre-8u131-windows-i586.exe in Windows installer;

    - updated README;

    * Toxtree-v3.0.0 (build date 15 Apr 2016):

    - included Revised Cramer Decision Tree module;

    - multiple bug fixes;

    * Toxtree-v3.0.0 (build date 07 Aug 2015):

    - included Revised Cramer Decision Tree module;

    - included jre-7u80-windows-i586.exe in Windows installer;

    - improved Java version detection/processing in the Windows installer;

    - updated manuals and README;

    * 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 <input file for normal open>

    java -jar Toxtree.jar -b <finput file for batch processing>

    - 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,
    1976) 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 (2015) by Ideaconsult Ltd., 4 Angel Kanchev St., 1000 Sofia, Bulgaria
