[octet-devel] Demystify 'in silico' cheminformatics and feature calculation identifier hashing

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Hi all,

Cross-Posting -> please reply ONLY TO the following lists, if your reply 
affects not your library and software package:
joe...@li... and
qsa...@li...

As you all know the 'in silico' chemistry is pretty complex and i've now 
implemented a trace back routine to identify how complex. This routine 
was implemented for JOELib2 (not JOELib1, so use: cvs co joelib2).
The complexity is more or less analogue to OpenBabel, since both 
libraries uses the same SMARTS-matching and text definition files.

As already discussed several times, we had serious problems to trace 
back algorithms (chemical expert systems) and feature calculation 
algorithms, because the complex dependencies trees hidden to the users. 
The only way to get a feeling for those dependencies was to read the 
source code.

This is even more serious for using algorithms depending on the 
underlying expert systems, like file conversion (force fields), QSAR 
descriptor (feature) calculation, SMARTS substructure search, and so on ...

Until now we were unable to formalize and assign a unique version number 
  to the applied algorithms. Hence this may be critical for QSAR, 
because one single change in the aromaticity typer (source code or text 
definition file) forwards those changes to all depending algorithms. But 
which one depends on the aromaticity, and affects this the algorithm of 
interest? Yes, definitely yes! Now, for JOELib2 we can calculate a 
hashed dependency tree identifier for each expert system, feature 
calculation algorithm and this version identifier is calculated 
automatically using the source code CVS tags, which are unique!
And i'm pretty proud to present this hack, because even with Java 
reflection this was tricky.

Here is an admonitory remark for the new year 2005 to all users:
'Never mess around with chemical expert systems, and never believe 
anyone telling you that a fingerprint is a simple 1D descriptor for 
screening.'
Why not?
1. '1D': As you can see the calculation requires the full chemical 
expert system and this is at least a 2D dependency, 1D is only valid for 
primitive elemental counts, without any neighborhood.
2. 'simple': even if you apply a 'simple' Query (e.g. SMARTS) matching 
task, the underlying complexity is far away from being simple (requires 
47 algorithms and feature calculation methods for 'SSKey3DS').

Here are two small examples and the full dependency tree can be 
calculated with JOELib2, 'sh joelibKernel.sh' (requires Java 1.5) and is 
available online:
http://www-ra.informatik.uni-tuebingen.de/software/joelib/KernelLog.txt

Now, the examples:
1. chemical expert system identifier:
jk:k-1566956551:softDependencies:joelib2.data.AtomTyper (992650183)
joelib2.data.AtomTyper http://joelib.sf.net 
joelib2/data/plain/atomtype.txt 1.1.1.1 2004-12-06_15-33-18

2. dependency for simple a 'simple' paharmacophore fingerprint:
dependency class is:     joelib2.feature.types.SSKey3DS
dependency version hash code is:   1113779298 (including chemistry 
kernel hash: -1566956551)
dependency algorithm complexity is at least:  47 (+ basic user input 
graph, + recursive dependencies, + data structure dependencies, + 
forgotten dependencies)

class joelib2.feature.types.SSKey3DS(version 1.4) depends on
  class joelib2.feature.types.count.AromaticBonds(version 1.2) depends on
   class joelib2.feature.types.atomlabel.AtomIsHydrogen(version 1.2)
   class joelib2.feature.types.bondlabel.BondInAromaticSystem(version 
1.3) depends on
    class joelib2.data.AromaticityTyper(version 1.4) depends on
     class joelib2.smarts.SMARTSPattern(version 1.3) depends on
      class joelib2.smarts.SMARTSParser(version 1.4) depends on 
(WARNING: recursively defined dependencies)
       class joelib2.feature.types.atomlabel.AtomBondOrderSum
       class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
       class joelib2.feature.types.atomlabel.AtomHeavyValence
       class joelib2.feature.types.atomlabel.AtomHybridisation
       class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
       class joelib2.feature.types.atomlabel.AtomImplicitValence
       class joelib2.feature.types.atomlabel.AtomInAromaticSystem
       class joelib2.feature.types.atomlabel.AtomInRing
       class joelib2.feature.types.atomlabel.AtomInRingsCount
       class joelib2.feature.types.atomlabel.AtomIsElectronegative
       class joelib2.feature.types.atomlabel.AtomIsHydrogen
       class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
       class joelib2.feature.types.bondlabel.BondInAromaticSystem
       class joelib2.feature.types.bondlabel.BondInRing
     class joelib2.feature.types.atomlabel.AtomHybridisation(version 
1.3) depends on
      class joelib2.data.AtomTyper(version 1.4) depends on
       class joelib2.smarts.SMARTSPattern(version 1.3) depends on
        class joelib2.smarts.SMARTSParser(version 1.4) depends on 
(WARNING: recursively defined dependencies)
         class joelib2.feature.types.atomlabel.AtomBondOrderSum
         class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
         class joelib2.feature.types.atomlabel.AtomHeavyValence
         class joelib2.feature.types.atomlabel.AtomHybridisation
         class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
         class joelib2.feature.types.atomlabel.AtomImplicitValence
         class joelib2.feature.types.atomlabel.AtomInAromaticSystem
         class joelib2.feature.types.atomlabel.AtomInRing
         class joelib2.feature.types.atomlabel.AtomInRingsCount
         class joelib2.feature.types.atomlabel.AtomIsElectronegative
         class joelib2.feature.types.atomlabel.AtomIsHydrogen
         class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
         class joelib2.feature.types.bondlabel.BondInAromaticSystem
         class joelib2.feature.types.bondlabel.BondInRing
     class joelib2.feature.types.atomlabel.AtomImplicitValence(version 
1.3) depends on
      class joelib2.data.AtomTyper(version 1.4) depends on
       class joelib2.smarts.SMARTSPattern(version 1.3) depends on
        class joelib2.smarts.SMARTSParser(version 1.4) depends on 
(WARNING: recursively defined dependencies)
         class joelib2.feature.types.atomlabel.AtomBondOrderSum
         class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
         class joelib2.feature.types.atomlabel.AtomHeavyValence
         class joelib2.feature.types.atomlabel.AtomHybridisation
         class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
         class joelib2.feature.types.atomlabel.AtomImplicitValence
         class joelib2.feature.types.atomlabel.AtomInAromaticSystem
         class joelib2.feature.types.atomlabel.AtomInRing
         class joelib2.feature.types.atomlabel.AtomInRingsCount
         class joelib2.feature.types.atomlabel.AtomIsElectronegative
         class joelib2.feature.types.atomlabel.AtomIsHydrogen
         class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
         class joelib2.feature.types.bondlabel.BondInAromaticSystem
         class joelib2.feature.types.bondlabel.BondInRing
     class joelib2.feature.types.atomlabel.AtomInRing(version 1.3) 
depends on
      class joelib2.ring.RingDetector(version 1.3)
     class joelib2.feature.types.atomlabel.AtomIsHydrogen(version 1.2)
     class joelib2.feature.types.bondlabel.BondInRing(version 1.2) 
depends on
      class joelib2.ring.RingDetector(version 1.3)
     class joelib2.feature.types.bondlabel.BondIsClosure(version 1.2)
  class joelib2.feature.types.atomlabel.AtomIsHeteroatom(version 1.2) 
depends on
   class joelib2.feature.types.atomlabel.AtomIsHalogen(version 1.3)
  class joelib2.ring.RingFinderSSSR(version 1.2) depends on
   class joelib2.feature.types.atomlabel.AtomInRing(version 1.3) depends on
    class joelib2.ring.RingDetector(version 1.3)
   class joelib2.feature.types.bondlabel.BondInRing(version 1.2) depends on
    class joelib2.ring.RingDetector(version 1.3)
   class joelib2.feature.types.bondlabel.BondIsClosure(version 1.2)
  class joelib2.feature.types.FractionRotatableBonds(version 1.3) depends on
   class joelib2.feature.types.atomlabel.AtomIsHydrogen(version 1.2)
   class joelib2.feature.types.bondlabel.BondIsRotor(version 1.3) depends on
    class joelib2.feature.types.atomlabel.AtomHeavyValence(version 1.3) 
depends on
     class joelib2.feature.types.atomlabel.AtomIsHydrogen(version 1.2)
    class joelib2.feature.types.atomlabel.AtomHybridisation(version 1.3) 
depends on
     class joelib2.data.AtomTyper(version 1.4) depends on
      class joelib2.smarts.SMARTSPattern(version 1.3) depends on
       class joelib2.smarts.SMARTSParser(version 1.4) depends on 
(WARNING: recursively defined dependencies)
        class joelib2.feature.types.atomlabel.AtomBondOrderSum
        class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
        class joelib2.feature.types.atomlabel.AtomHeavyValence
        class joelib2.feature.types.atomlabel.AtomHybridisation
        class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
        class joelib2.feature.types.atomlabel.AtomImplicitValence
        class joelib2.feature.types.atomlabel.AtomInAromaticSystem
        class joelib2.feature.types.atomlabel.AtomInRing
        class joelib2.feature.types.atomlabel.AtomInRingsCount
        class joelib2.feature.types.atomlabel.AtomIsElectronegative
        class joelib2.feature.types.atomlabel.AtomIsHydrogen
        class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
        class joelib2.feature.types.bondlabel.BondInAromaticSystem
        class joelib2.feature.types.bondlabel.BondInRing
  class joelib2.feature.types.count.HBA1(version 1.2) depends on
   class joelib2.smarts.ProgrammableAtomTyper(version 1.4) depends on
    class joelib2.smarts.SMARTSPattern(version 1.3) depends on
     class joelib2.smarts.SMARTSParser(version 1.4) depends on (WARNING: 
recursively defined dependencies)
      class joelib2.feature.types.atomlabel.AtomBondOrderSum
      class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
      class joelib2.feature.types.atomlabel.AtomHeavyValence
      class joelib2.feature.types.atomlabel.AtomHybridisation
      class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
      class joelib2.feature.types.atomlabel.AtomImplicitValence
      class joelib2.feature.types.atomlabel.AtomInAromaticSystem
      class joelib2.feature.types.atomlabel.AtomInRing
      class joelib2.feature.types.atomlabel.AtomInRingsCount
      class joelib2.feature.types.atomlabel.AtomIsElectronegative
      class joelib2.feature.types.atomlabel.AtomIsHydrogen
      class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
      class joelib2.feature.types.bondlabel.BondInAromaticSystem
      class joelib2.feature.types.bondlabel.BondInRing
  class joelib2.feature.types.count.HBA2(version 1.2) depends on
   class joelib2.smarts.ProgrammableAtomTyper(version 1.4) depends on
    class joelib2.smarts.SMARTSPattern(version 1.3) depends on
     class joelib2.smarts.SMARTSParser(version 1.4) depends on (WARNING: 
recursively defined dependencies)
      class joelib2.feature.types.atomlabel.AtomBondOrderSum
      class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
      class joelib2.feature.types.atomlabel.AtomHeavyValence
      class joelib2.feature.types.atomlabel.AtomHybridisation
      class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
      class joelib2.feature.types.atomlabel.AtomImplicitValence
      class joelib2.feature.types.atomlabel.AtomInAromaticSystem
      class joelib2.feature.types.atomlabel.AtomInRing
      class joelib2.feature.types.atomlabel.AtomInRingsCount
      class joelib2.feature.types.atomlabel.AtomIsElectronegative
      class joelib2.feature.types.atomlabel.AtomIsHydrogen
      class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
      class joelib2.feature.types.bondlabel.BondInAromaticSystem
      class joelib2.feature.types.bondlabel.BondInRing
  class joelib2.smarts.SMARTSPattern(version 1.3) depends on
   class joelib2.smarts.SMARTSParser(version 1.4) depends on (WARNING: 
recursively defined dependencies)
    class joelib2.feature.types.atomlabel.AtomBondOrderSum
    class joelib2.feature.types.atomlabel.AtomExplicitHydrogenCount
    class joelib2.feature.types.atomlabel.AtomHeavyValence
    class joelib2.feature.types.atomlabel.AtomHybridisation
    class joelib2.feature.types.atomlabel.AtomImplicitHydrogenCount
    class joelib2.feature.types.atomlabel.AtomImplicitValence
    class joelib2.feature.types.atomlabel.AtomInAromaticSystem
    class joelib2.feature.types.atomlabel.AtomInRing
    class joelib2.feature.types.atomlabel.AtomInRingsCount
    class joelib2.feature.types.atomlabel.AtomIsElectronegative
    class joelib2.feature.types.atomlabel.AtomIsHydrogen
    class joelib2.feature.types.atomlabel.AtomKekuleBondOrderSum
    class joelib2.feature.types.bondlabel.BondInAromaticSystem
    class joelib2.feature.types.bondlabel.BondInRing

And a Happy New Year to all !

Kind regards, Joerg
-- 
Dipl. Chem. Joerg K. Wegner
Center of Bioinformatics Tuebingen (ZBIT)
Department of Computer Architecture
Univ. Tuebingen, Sand 1, D-72076 Tuebingen, Germany
Phone: (+49/0) 7071 29 78970
Fax: (+49/0) 7071 29 5091
E-Mail: mailto:we...@in...
WWW:    http://www-ra.informatik.uni-tuebingen.de
--
Never mistake motion for action.
                                     (E. Hemingway)

Never mistake action for meaningful action.
                                (Hugo Kubinyi,2004)