// ----------------- private methods -----------------
// make sure that for a single molecule, the way that the hashes are created & folded is consistent with a reference
private static void CheckFP(string molstr, CircularFingerprinterClass classType, int folding, int[] refHash)
{
var strType = classType == CircularFingerprinterClass.ECFP6 ? "ECFP6" : "FCFP6";
WriteLine($"Comparing hash codes for {strType}/folding={folding}");
var mol = new EnumerableSDFReader(new StringReader(molstr), ChemObjectBuilder.Instance).First();
var model = new Bayesian(classType, folding);
model.AddMolecule(mol, false);
var calcHash = model.Training[0];
var same = calcHash.Length == refHash.Length;
if (same)
{
for (int n = 0; n < calcHash.Length; n++)
{
if (calcHash[n] != refHash[n])
{
same = false;
break;
}
}
}
if (!same)
{
WriteLine($" ** calculated: {ArrayStr(calcHash)}");
WriteLine($" ** reference: {ArrayStr(refHash)}");
throw new CDKException("Hashes differ.");
}
}
// compares a series of molecules for folding fingerprints being literally identical
private static void CompareFolding(string sdfile, string fpField, CircularFingerprinterClass classType, int folding)
{
WriteLine($"[{sdfile}] calculation of: {fpField}");
using (var ins = ResourceLoader.GetAsStream($"NCDK.Data.CDD.{sdfile}"))
{
var rdr = new EnumerableSDFReader(ins, ChemObjectBuilder.Instance);
int row = 0;
foreach (var mol in rdr)
{
row++;
var model = new Bayesian(classType, folding);
model.AddMolecule(mol, false);
var hashes = model.Training[0];
var gotHashes = ArrayStr(hashes);
var reqHashes = (string)mol.GetProperties()[fpField];
Assert.AreEqual(reqHashes, gotHashes, $"Folded hashes do not match reference at {row}.");
}
}
}
/// <summary>
/// Instantiate a Bayesian model with no data.
/// </summary>
/// <param name="classType">one of the <see cref="CircularFingerprinterClass"/> enum</param>
/// <param name="folding">the maximum number of fingerprint bits, which must be a power of 2 (e.g. 1024, 2048) or 0 for no folding</param>
public Bayesian(CircularFingerprinterClass classType, int folding)
{
this.ClassType = classType;
this.Folding = folding;
// make sure the folding is valid
bool bad = false;
if (folding > 0)
{
for (int f = folding; f > 0; f = f >> 1)
{
if ((f & 1) == 1 && f != 1)
{
bad = true;
break;
}
}
}
if (folding < 0 || bad)
{
throw new ArithmeticException("Fingerprint folding " + folding + " invalid: must be 0 or power of 2.");
}
}
private void RunTest(string sdfile, string actvField, CircularFingerprinterClass classType, int folding, int xval, string modelFN, bool perceiveStereo)
{
WriteLine("[" + modelFN + "]");
WriteLine(" Loading " + sdfile);
try
{
var model = new Bayesian(classType, folding)
{
PerceiveStereo = perceiveStereo
};
int row = 0, numActives = 0;
using (var rdr = new EnumerableSDFReader(ResourceLoader.GetAsStream($"NCDK.Data.CDD.{sdfile}"), ChemObjectBuilder.Instance))
{
foreach (var mol in rdr)
{
row++;
var stractv = (string)mol.GetProperties()[actvField];
int active = stractv.Equals("true", StringComparison.Ordinal) ? 1 : stractv.Equals("false", StringComparison.Ordinal) ? 0 : int.Parse(stractv, NumberFormatInfo.InvariantInfo);
if (active != 0 && active != 1)
{
throw new CDKException("Activity field not found or invalid");
}
model.AddMolecule(mol, active == 1);
numActives += active;
}
}
WriteLine($" Training with {row} rows, {numActives} actives, {(row - numActives)} inactives");
model.Build();
if (xval == 3)
{
model.ValidateThreeFold();
}
else if (xval == 5)
{
model.ValidateFiveFold();
}
else
{
model.ValidateLeaveOneOut();
}
WriteLine($" Validation: ROC AUC={model.RocAUC}");
WriteLine($" Parsing reference model");
//FileReader frdr=new FileReader(modelFN);
Bayesian reference;
using (var mrdr = new StreamReader(ResourceLoader.GetAsStream($"NCDK.Data.CDD.{modelFN}")))
{
reference = Bayesian.Deserialise(mrdr);
}
// start comparing the details...
bool failed = false;
if (model.Folding != reference.Folding)
{
WriteLine($" ** reference folding size={reference.Folding}");
failed = true;
}
if (model.TrainingSize != reference.TrainingSize)
{
WriteLine($" ** reference training size={reference.TrainingSize}");
failed = true;
}
if (model.TrainingActives != reference.TrainingActives)
{
WriteLine($" ** reference training actives={reference.TrainingActives}");
failed = true;
}
if (model.RocType != reference.RocType)
{
WriteLine($" ** reference ROC type={reference.RocType}");
failed = true;
}
if (!DblEqual(model.RocAUC, reference.RocAUC))
{
WriteLine($" ** reference ROC AUC={reference.RocAUC}");
failed = true;
}
if (Math.Abs(model.LowThreshold - reference.LowThreshold) > 0.00000000000001)
{
WriteLine($" ** reference lowThresh={reference.LowThreshold} different to calculated {model.LowThreshold}");
failed = true;
}
if (Math.Abs(model.HighThreshold - reference.HighThreshold) > 0.00000000000001)
{
WriteLine($" ** reference highThresh={reference.HighThreshold} different to calculated {model.HighThreshold}");
failed = true;
}
// make sure individual hash bit contributions match
var mbits = model.Contributions;
var rbits = reference.Contributions;
if (mbits.Count != rbits.Count)
{
WriteLine($" ** model has {mbits.Count} contribution bits, reference has {rbits.Count}");
failed = true;
}
foreach (var h in mbits.Keys)
{
if (!rbits.ContainsKey(h))
{
WriteLine($" ** model hash bit {h} not found in reference");
failed = true;
break; // one is enough
}
}
foreach (var h in rbits.Keys)
{
if (!mbits.ContainsKey(h))
{
WriteLine($" ** reference hash bit {h} not found in model");
failed = true;
break; // one is enough
}
}
foreach (var h in mbits.Keys)
{
if (rbits.ContainsKey(h))
{
double c1 = mbits[h], c2 = rbits[h];
if (!DblEqual(c1, c2))
{
WriteLine($" ** contribution for bit {h}: model={c1}, reference={c2}");
failed = true;
break; // one is enough
}
}
}
if (failed)
{
throw new CDKException("Comparison to reference failed");
}
}
catch (CDKException)
{
throw;
}
catch (Exception ex)
{
throw new CDKException("Test failed", ex);
}
}
// performs a bulk test: loads an SDfile, builds a model with the given parameters, and compares it to a reference model
// that has been previously serialised
private void RunTest(string sdfile, string actvField, CircularFingerprinterClass classType, int folding, int xval, string modelFN)
{
RunTest(sdfile, actvField, classType, folding, xval, modelFN, false);
}
// ----------------- public methods -----------------
/// <summary>
/// Instantiate a Bayesian model with no data.
/// </summary>
/// <param name="classType">one of the CircularFingerprinter.CLASS_* constants</param>
public Bayesian(CircularFingerprinterClass classType)
{
this.ClassType = classType;
}
/// <summary>
/// BuildTest
/// </summary>
public static void BuildTest()
{
CircularFingerprinter cfp = null;
CircularFingerprinterClass FpClass = CircularFingerprinterClass.ECFP6; // FP diameter
int FpLen = 2048; // folded binary fp length
IAtomContainer mol, mol2;
//string molfile = FileUtil.ReadFile(@"C:\Download\CorpId-12345.mol");
//java.io.StringReader sr = new java.io.StringReader(molfile);
//if (Lex.Contains(molfile, "v2000"))
// cor = new MDLV2000Reader(sr);
//else
// cor = new MDLV3000Reader(sr);
//cor.setReaderMode(IChemObjectReader.Mode.RELAXED);
//ac = (IAtomContainer)cor.read(new AtomContainer());
//cor.close();
FpClass = CircularFingerprinterClass.ECFP4; // debug
cfp = new CircularFingerprinter(FpClass, FpLen);
StreamReader reader = new StreamReader(@"C:\Download\CorpId-12345.mol");
//FileReader FileReader = new FileReader(@"C:\Download\V3000 Mols.sdf");
EnumerableSDFReader rdr = new EnumerableSDFReader(reader.BaseStream, ChemObjectBuilder.Instance);
rdr.ReaderMode = ChemObjectReaderMode.Relaxed;
IEnumerator <IAtomContainer> cursor = rdr.GetEnumerator();
while (cursor.MoveNext())
{
mol = cursor.Current;
mol = CdkMol.GetLargestMoleculeFragment(mol);
ICountFingerprint cfp1 = cfp.GetCountFingerprint(mol); // get hash values and counts for each
cfp.Calculate(mol);
int fpCount = cfp.FPCount;
for (int fpi = 0; fpi < fpCount; fpi++) // gets
{
CircularFingerprint cfp2 = cfp.GetFP(fpi); // gets hash, iteration and lists of atoms (dups appear multiple times)
}
IBitFingerprint bfp = cfp.GetBitFingerprint(mol);
BitArray bs = bfp.AsBitSet();
int bsCard = bfp.Cardinality;
long bsSize = bfp.Length;
continue;
}
reader.Close();
return;
//java.io.StringReader sr = new java.io.StringReader(molfile);
//AtomContainer mol = new AtomContainer();
//mol.addAtom(new Atom("C"));
//mol.addAtom(new Atom("H"));
//mol.addAtom(new Atom("H"));
//mol.addAtom(new Atom("H"));
//mol.addAtom(new Atom("H"));
//mol.addBond(new Bond(mol.getAtom(0), mol.getAtom(1)));
//mol.addBond(new Bond(mol.getAtom(0), mol.getAtom(2)));
//mol.addBond(new Bond(mol.getAtom(0), mol.getAtom(3)));
//mol.addBond(new Bond(mol.getAtom(0), mol.getAtom(4)));
//FileReader FileReader = new FileReader(@"C:\Download\CorpId-12345.mol");
//MolReader mr = new MolReader(FileReader, DefaultChemObjectBuilder.getInstance());
//java.io.StringReader sr = new java.io.StringReader(molfile);
//IMol m = (IMol)mr.next();
//FileReader.close();
}
/// <summary>
/// Build fingerprint
/// </summary>
/// <param name="mol"></param>
public static BitSetFingerprint BuildBitSetFingerprint(
IAtomContainer mol,
FingerprintType fpType,
int fpSubtype = -1,
int fpLen = -1)
{
// Data for Tanimoto similarity using various fingerprint types for CorpId 123456 query.
// Cart - Standard MDL Oracle Cartridge scores
//
// Similarity Score
// ------------------------------------------------
// Size -> 192 896 1024 1024 128 1024 320
// CorpId Cart MACCS PbChm ECFP4 EXT EState Basic Sbstr
// ------ ---- ---- ---- ---- ---- ---- ---- ----
// 123456 0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00
// 123456 0.99 0.98 0.96 0.77 0.95 1.00 0.95 1.00
// 123456 0.99 0.98 0.96 0.77 0.95 1.00 0.94 1.00
// 123456 0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00
// 123456 0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00
// 123456 0.99 0.91 1.00 0.81 1.00 1.00 1.00 1.00
// 123456 0.98 0.95 1.00 0.74 0.92 1.00 0.93 0.94
// 123456 0.98 1.00 1.00 1.00 1.00 1.00 1.00 1.00
// 123456 0.98 1.00 1.00 1.00 1.00 1.00 1.00 1.00
// 123456 0.98 1.00 0.83 0.76 0.77 0.90 0.76 0.94
// LSH Bin Count - The number of LSH bins (of 25) that match the query bin values
//--------------
// CorpId MAC PbC ECFP EX
// ------ --- --- --- ---
// 123456 25 25 25 25
// 123456 25 20 7 16
// 123456 25 20 9 19
// 123456 25 25 25 25
// 123456 25 25 25 25
// 123456 20 25 9 25
// 123456 21 25 11 17
// 123456 25 25 25 25
// 123456 25 25 25 25
// 123456 25 9 6 11
// Data for Tanimoto similarity using various Circular fingerprint types.
// Using 2 molecules where the 2nd just has an added methyl group.
//
// Measure Score
// -------- -----
// ECFP0 1.00
// ECFP2 .88
// ECFP4 .75
// ECFP6 .64
// FCFP0 1.00
// FCFP2 .92
// FCFP4 .84
// FCFP6 .74
IFingerprinter ifptr = null;
IBitFingerprint ibfp = null;
BitSetFingerprint bfp = null;
IAtomContainer mol2;
string s = "";
DateTime t0 = DateTime.Now;
double getFptrTime = 0, buildFpTime = 0;
if (fpType == FingerprintType.Basic) // size = 1024
{
ifptr = new Fingerprinter();
}
else if (fpType == FingerprintType.Circular) // size variable
{
CircularFingerprinterClass cfpClass = (CircularFingerprinterClass)fpSubtype;
if (cfpClass < CircularFingerprinterClass.ECFP0 || cfpClass > CircularFingerprinterClass.ECFP6)
{
cfpClass = (CircularFingerprinterClass)CircularFingerprintType.DefaultCircularClass; // default class
}
if (fpLen < 0)
{
fpLen = CircularFingerprintType.DefaultCircularLength; // default length
}
ifptr = new CircularFingerprinter(cfpClass, fpLen);
//CircularFingerprinter cfp = (CircularFingerprinter)ifptr;
//ICountFingerprint cntFp = cfp.getCountFingerprint(mol); // debug
//s = CircularFpToString(cfp); // debug
}
else if (fpType == FingerprintType.Extended) // size = 1024
{
ifptr = new ExtendedFingerprinter(); // use DEFAULT_SIZE and DEFAULT_SEARCH_DEPTH
}
else if (fpType == FingerprintType.EState) // size = 128
{
ifptr = new EStateFingerprinter(); // use DEFAULT_SIZE and DEFAULT_SEARCH_DEPTH
}
else if (fpType == FingerprintType.MACCS) // size = 192
{
if (MACCSFp == null)
{
MACCSFp = new MACCSFingerprinter();
}
ifptr = MACCSFp;
}
else if (fpType == FingerprintType.PubChem) // size = 896
{
//IChemObjectBuilder builder = DefaultChemObjectBuilder.getInstance();
ifptr = new PubchemFingerprinter();
}
else if (fpType == FingerprintType.ShortestPath) // size =
{
ifptr = new ShortestPathFingerprinter(); // fails with atom type issue for many structures (e.g. 123456)
}
else if (fpType == FingerprintType.Signature) // size =
{
ifptr = new SignatureFingerprinter(); // can't convert array fingerprint to bitsetfingerprint
}
else if (fpType == FingerprintType.Substructure) // size = 320
{
ifptr = new SubstructureFingerprinter();
}
else
{
throw new Exception("Invalid CdkFingerprintType: " + fpType);
}
getFptrTime = TimeOfDay.Delta(ref t0);
ibfp = ifptr.GetBitFingerprint(mol);
bfp = (BitSetFingerprint)ibfp;
buildFpTime = TimeOfDay.Delta(ref t0);
//long size = bfp.size();
//int card = bfp.Cardinality;
return(bfp);
}