/// <summary>
/// Validates input sequences and gap penalties.
/// Checks that input sequences use the same alphabet.
/// Checks that each symbol in the input sequences exists in the similarity matrix.
/// Checks that gap penalties are less than or equal to 0.
/// Throws exception if sequences fail these checks.
/// Writes warning to ApplicationLog if gap penalty or penalties are positive.
/// </summary>
/// <param name="inputA">First input sequence.</param>
/// <param name="inputB">Second input sequence.</param>
protected void ValidateAlignInput(ISequence inputA, ISequence inputB)
{
if (inputA == null)
{
throw new ArgumentNullException("inputA");
}
if (inputB == null)
{
throw new ArgumentNullException("inputB");
}
if (!Alphabets.CheckIsFromSameBase(inputA.Alphabet, inputB.Alphabet))
{
throw new ArgumentException(Properties.Resource.InputAlphabetsMismatch);
}
if (null == this.InternalSimilarityMatrix)
{
throw new ArgumentException(Properties.Resource.SimilarityMatrixCannotBeNull);
}
if (!this.InternalSimilarityMatrix.ValidateSequence(inputA))
{
throw new ArgumentException(Properties.Resource.FirstInputSequenceMismatchSimilarityMatrix);
}
if (!this.InternalSimilarityMatrix.ValidateSequence(inputB))
{
throw new ArgumentException(Properties.Resource.SecondInputSequenceMismatchSimilarityMatrix);
}
}
/// <summary>
/// Build the HTTP content for the request based on the parameters
/// </summary>
/// <returns>The request.</returns>
public HttpContent BuildRequest(BlastRequestParameters blastParams)
{
if (string.IsNullOrWhiteSpace(blastParams.Database))
{
throw new ArgumentException("Database must be supplied.");
}
if (string.IsNullOrWhiteSpace(blastParams.Program))
{
throw new ArgumentException("Program must be supplied.");
}
if (blastParams.Sequences.Count == 0)
{
throw new ArgumentException("Must have at least one sequence.");
}
// Check that all sequences are same alphabet
if (blastParams.Sequences.Count > 1)
{
ISequence primary = blastParams.Sequences[0];
for (int i = 1; i < blastParams.Sequences.Count; i++)
{
if (!Alphabets.CheckIsFromSameBase(primary.Alphabet, blastParams.Sequences[i].Alphabet))
{
throw new ArgumentException("Sequences must all share the same base alphabet.");
}
}
}
var data = new List <KeyValuePair <string, string> > {
this.CreateKVP("CMD", "Put")
};
if (blastParams.Program == BlastProgram.Megablast)
{
data.Add(this.CreateKVP("PROGRAM", BlastProgram.Blastn));
data.Add(this.CreateKVP("MEGABLAST", "ON"));
}
else
{
data.Add(this.CreateKVP("PROGRAM", blastParams.Program));
}
data.Add(this.CreateKVP("DATABASE", blastParams.Database));
data.AddRange(blastParams.ExtraParameters);
// Add the sequences.
StringBuilder sb = new StringBuilder();
foreach (var seq in blastParams.Sequences)
{
sb.Append(seq.ConvertToString());
}
data.Add(this.CreateKVP("QUERY", sb.ToString()));
return(new FormUrlEncodedContent(data));
}
/// <summary>
/// Sets up fields for the assembly process.
/// </summary>
private void Initialize()
{
this.currentStep = 0;
this.progressTimer = new Timer(ProgressTimerInterval);
this.progressTimer.Elapsed += new ElapsedEventHandler(this.ProgressTimerElapsed);
this.statusMessage = string.Format(CultureInfo.CurrentCulture, Properties.Resource.InitializingStarted, DateTime.Now);
this.RaiseStatusEvent();
// Reset parameters not set by user, based on sequenceReads
if (this.AllowKmerLengthEstimation)
{
this.kmerLength = EstimateKmerLength(this.sequenceReads);
}
else
{
if (this.kmerLength <= 0)
{
throw new InvalidOperationException(Properties.Resource.KmerLength);
}
try
{
if (!Alphabets.CheckIsFromSameBase(this.sequenceReads.First().Alphabet, Alphabets.DNA))
{
throw new InvalidOperationException(Properties.Resource.CannotAssembleSequenceType);
}
}
catch (Exception e)
{
if (e.InnerException != null && !string.IsNullOrEmpty(e.InnerException.Message))
{
throw e.InnerException;
}
else
{
throw;
}
}
}
if (this.dangleThreshold == -1)
{
this.dangleThreshold = this.kmerLength + 1;
}
if (this.redundantPathLengthThreshold == -1)
{
// Reference for default threshold for redundant path purger:
// ABySS Release Notes 1.1.2 - "Pop bubbles shorter than N bp. The default is b=3*(k + 1)."
this.redundantPathLengthThreshold = 3 * (this.kmerLength + 1);
}
this.InitializeDefaultGraphModifiers();
this.statusMessage = string.Format(CultureInfo.CurrentCulture, Properties.Resource.InitializingEnded, DateTime.Now);
this.RaiseStatusEvent();
}
/// <summary>
/// Validates input sequences and gap penalties.
/// Checks that input sequences use the same alphabet.
/// Checks that each symbol in the input sequences exists in the similarity matrix.
/// Checks that gap penalties are less than or equal to 0.
/// Throws exception if sequences fail these checks.
/// Writes warning to ApplicationLog if gap penalty or penalties are positive.
/// </summary>
/// <param name="inputA">First input sequence.</param>
/// <param name="inputB">Second input sequence.</param>
protected void ValidateAlignInput(ISequence inputA, ISequence inputB)
{
if (inputA == null)
{
throw new ArgumentNullException("inputA");
}
if (inputB == null)
{
throw new ArgumentNullException("inputB");
}
if (!Alphabets.CheckIsFromSameBase(inputA.Alphabet, inputB.Alphabet))
{
Trace.Report(Properties.Resource.InputAlphabetsMismatch);
throw new ArgumentException(Properties.Resource.InputAlphabetsMismatch);
}
if (null == internalSimilarityMatrix)
{
Trace.Report(Properties.Resource.SimilarityMatrixCannotBeNull);
throw new ArgumentException(Properties.Resource.SimilarityMatrixCannotBeNull);
}
if (!internalSimilarityMatrix.ValidateSequence(inputA))
{
Trace.Report(Properties.Resource.FirstInputSequenceMismatchSimilarityMatrix);
throw new ArgumentException(Properties.Resource.FirstInputSequenceMismatchSimilarityMatrix);
}
if (!internalSimilarityMatrix.ValidateSequence(inputB))
{
Trace.Report(Properties.Resource.SecondInputSequenceMismatchSimilarityMatrix);
throw new ArgumentException(Properties.Resource.SecondInputSequenceMismatchSimilarityMatrix);
}
// Warning if gap penalty > 0
if (GapOpenCost > 0)
{
ApplicationLog.WriteLine("Gap Open Penalty {0} > 0, possible error", GapOpenCost);
}
if (GapExtensionCost > 0)
{
ApplicationLog.WriteLine("Gap Extension Penalty {0} > 0, possible error", GapExtensionCost);
}
}
/// <summary>
/// Construct an aligner
/// </summary>
/// <param name="sequences">input sequences</param>
/// <param name="kmerLength">positive integer of kmer length</param>
/// <param name="distanceFunctionName">enum: distance function name</param>
/// <param name="hierarchicalClusteringMethodName">enum: cluster update method</param>
/// <param name="profileAlignerMethodName">enum: profile-profile aligner name</param>
/// <param name="profileFunctionName">enum: profile-profile distance function</param>
/// <param name="similarityMatrix">similarity matrix</param>
/// <param name="gapOpenPenalty">negative gapOpenPenalty</param>
/// <param name="gapExtendPenalty">negative gapExtendPenalty</param>
/// <param name="numberOfPartitions">the number of partitions in dynamic programming</param>
/// <param name="degreeOfParallelism">degree of parallelism option for parallel extension</param>
public PAMSAMMultipleSequenceAligner(
IList <ISequence> sequences,
int kmerLength,
DistanceFunctionTypes distanceFunctionName,
UpdateDistanceMethodsTypes hierarchicalClusteringMethodName,
ProfileAlignerNames profileAlignerMethodName,
ProfileScoreFunctionNames profileFunctionName,
SimilarityMatrix similarityMatrix,
int gapOpenPenalty,
int gapExtendPenalty,
int numberOfPartitions,
int degreeOfParallelism)
{
Performance.Start();
if (null == sequences)
{
throw new ArgumentNullException("sequences");
}
if (sequences.Count == 0)
{
throw new ArgumentException("Empty input sequences");
}
// Set parallel extension option
if (degreeOfParallelism <= 0)
{
throw new ArgumentException("Invalid parallel degree parameter");
}
PAMSAMMultipleSequenceAligner.parallelOption = new ParallelOptions {
MaxDegreeOfParallelism = degreeOfParallelism
};
if (numberOfPartitions <= 0)
{
throw new ArgumentException("Invalid number of partition parameter");
}
_numberOfPartitions = numberOfPartitions;
// Validate data type
_alphabet = sequences[0].Alphabet;
Parallel.For(1, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
if (!Alphabets.CheckIsFromSameBase(sequences[i].Alphabet, _alphabet))
{
throw new ArgumentException("Inconsistent sequence alphabet");
}
});
List <String> similarityMatrixDNA = new List <String>();
similarityMatrixDNA.Add("AmbiguousDNA");
List <String> similarityMatrixRNA = new List <String>();
similarityMatrixRNA.Add("AmbiguousRNA");
List <String> similarityMatrixProtein = new List <String>();
similarityMatrixProtein.Add("BLOSUM45");
similarityMatrixProtein.Add("BLOSUM50");
similarityMatrixProtein.Add("BLOSUM62");
similarityMatrixProtein.Add("BLOSUM80");
similarityMatrixProtein.Add("BLOSUM90");
similarityMatrixProtein.Add("PAM250");
similarityMatrixProtein.Add("PAM30");
similarityMatrixProtein.Add("PAM70");
if (_alphabet is DnaAlphabet)
{
if (!similarityMatrixDNA.Contains(similarityMatrix.Name))
{
throw new ArgumentException("Inconsistent similarity matrix");
}
}
else if (_alphabet is ProteinAlphabet)
{
if (!similarityMatrixProtein.Contains(similarityMatrix.Name))
{
throw new ArgumentException("Inconsistent similarity matrix");
}
}
else if (_alphabet is RnaAlphabet)
{
if (!similarityMatrixRNA.Contains(similarityMatrix.Name))
{
throw new ArgumentException("Inconsistent similarity matrix");
}
}
else
{
throw new ArgumentException("Invalid alphabet");
}
// Initialize parameters
_kmerLength = kmerLength;
_distanceFunctionName = distanceFunctionName;
_hierarchicalClusteringMethodName = hierarchicalClusteringMethodName;
_profileAlignerName = profileAlignerMethodName;
_profileProfileFunctionName = profileFunctionName;
SimilarityMatrix = similarityMatrix;
GapOpenCost = gapOpenPenalty;
GapExtensionCost = gapExtendPenalty;
MsaUtils.SetProfileItemSets(_alphabet);
Performance.Snapshot("Start Aligning");
// Work...
Align(sequences);
}
/// <summary>
/// Sets up fields for the assembly process.
/// </summary>
protected void Initialize()
{
this._currentStep = 0;
this._progressTimer = new Timer(ProgressTimerInterval);
this._progressTimer.Elapsed += this.ProgressTimerElapsed;
this._statusMessage = string.Format(CultureInfo.CurrentCulture, Properties.Resource.InitializingStarted, DateTime.Now);
this.RaiseStatusEvent();
// Reset parameters not set by user, based on sequenceReads
if (this.AllowKmerLengthEstimation)
{
this._kmerLength = EstimateKmerLength(this._sequenceReads);
}
else
{
if (this._kmerLength <= 0)
{
throw new InvalidOperationException(Properties.Resource.KmerLength);
}
try
{
if (!Alphabets.CheckIsFromSameBase(this._sequenceReads.First().Alphabet, Alphabets.DNA))
{
throw new InvalidOperationException(Properties.Resource.CannotAssembleSequenceType);
}
}
catch (Exception e)
{
if (e.InnerException != null && !string.IsNullOrEmpty(e.InnerException.Message))
{
throw e.InnerException;
}
throw;
}
}
// TODO: Force an odd kmer length to avoid palindromes
// Need to evaluate this more - for now rely on the user to
// not pass in bad data.
//if (_kmerLength % 2 == 0)
// _kmerLength++;
// Enforce our boundaries (same as DeBruijnGraph code)
_kmerLength = Math.Max(1, Math.Min(DeBruijnGraph.MaxKmerLength, _kmerLength));
if (this.DanglingLinksThreshold == -1)
{
this.DanglingLinksThreshold = this._kmerLength + 1;
}
if (this.RedundantPathLengthThreshold == -1)
{
// Reference for default threshold for redundant path purger:
// ABySS Release Notes 1.1.2 - "Pop bubbles shorter than N bp. The default is b=3*(k + 1)."
this.RedundantPathLengthThreshold = 3 * (this._kmerLength + 1);
}
this.InitializeDefaultGraphModifiers();
this._statusMessage = string.Format(CultureInfo.CurrentCulture, Properties.Resource.InitializingEnded, DateTime.Now);
this.RaiseStatusEvent();
}
/// <summary>
/// For optimal graph formation, k-mer length should not be less
/// than half the length of the longest input sequence and
/// cannot be more than the length of the shortest input sequence.
/// Reference for estimating kmerlength from reads: Supplement material from
/// publication "ABySS: A parallel assembler for short read sequence data".
/// </summary>
/// <param name="sequences">List of input sequences.</param>
/// <returns>Estimated optimal kmer length.</returns>
public static int EstimateKmerLength(IEnumerable <ISequence> sequences)
{
if (sequences == null)
{
throw new ArgumentNullException("sequences");
}
if (!Alphabets.CheckIsFromSameBase(sequences.First().Alphabet, Alphabets.DNA))
{
throw new InvalidOperationException(Properties.Resource.CannotAssembleSequenceType);
}
long minSeqLength = long.MaxValue, maxSeqLength = 0;
// Get the min/max ranges for the sequences
foreach (ISequence seq in sequences)
{
long seqCount = seq.Count;
if (minSeqLength > seqCount)
{
minSeqLength = seqCount;
}
if (maxSeqLength < seqCount)
{
maxSeqLength = seqCount;
}
}
// for optimal purpose, kmer length should be more than half of longest sequence
float minLengthOfKmer = Math.Max(1, maxSeqLength / 2);
float maxLengthOfKmer = minSeqLength;
int kmerLength = minLengthOfKmer < maxLengthOfKmer
? (int)Math.Ceiling((minLengthOfKmer + maxLengthOfKmer) / 2)
: (int)Math.Floor(maxLengthOfKmer);
// Make the kmer odd to avoid palindromes.
if (kmerLength % 2 == 0)
{
kmerLength++;
if (kmerLength > maxLengthOfKmer)
{
kmerLength -= 2;
}
if (kmerLength <= 0)
{
kmerLength = 1;
}
}
// Final sanity checks.
if (maxLengthOfKmer < kmerLength)
{
throw new InvalidOperationException(Properties.Resource.InappropriateKmerLength);
}
if (kmerLength <= 0)
{
throw new InvalidOperationException(Properties.Resource.KmerLength);
}
// Bound to our max size based on data handling.
return(kmerLength > DeBruijnGraph.MaxKmerLength ? DeBruijnGraph.MaxKmerLength : kmerLength);
}
/// <summary>
/// This method assigns the alphabet from the input sequences
/// </summary>
/// <param name="sequences">Input sequences</param>
/// <param name="similarityMatrix">Matrix to use for similarity comparisons</param>
/// <param name="fixSimilarityMatrixErrors">True to fix any similarity matrix issue related to the alphabet.</param>
private void SetAlphabet(IList <ISequence> sequences, SimilarityMatrix similarityMatrix, bool fixSimilarityMatrixErrors)
{
if (sequences.Count == 0)
{
throw new ArgumentException("Empty input sequences");
}
// Validate data type
_alphabet = Alphabets.GetAmbiguousAlphabet(sequences[0].Alphabet);
Parallel.For(1, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
if (!Alphabets.CheckIsFromSameBase(sequences[i].Alphabet, _alphabet))
{
throw new ArgumentException("Inconsistent sequence alphabet");
}
});
SimilarityMatrix bestSimilarityMatrix = null;
if (_alphabet is DnaAlphabet)
{
bestSimilarityMatrix = new SimilarityMatrix(SimilarityMatrix.StandardSimilarityMatrix.AmbiguousDna);
}
else if (_alphabet is RnaAlphabet)
{
bestSimilarityMatrix = new SimilarityMatrix(SimilarityMatrix.StandardSimilarityMatrix.AmbiguousRna);
}
else if (_alphabet is ProteinAlphabet)
{
bestSimilarityMatrix = new SimilarityMatrix(SimilarityMatrix.StandardSimilarityMatrix.Blosum50);
}
// Check or assign the similarity matrix.
if (similarityMatrix == null)
{
SimilarityMatrix = bestSimilarityMatrix;
if (SimilarityMatrix == null)
{
throw new ArgumentException("Unknown alphabet - could not choose SimilarityMatrix.");
}
}
else
{
List <String> similarityMatrixDNA = new List <String> {
"AmbiguousDNA"
};
List <String> similarityMatrixRNA = new List <String> {
"AmbiguousRNA"
};
List <String> similarityMatrixProtein = new List <String> {
"BLOSUM45", "BLOSUM50", "BLOSUM62", "BLOSUM80", "BLOSUM90", "PAM250", "PAM30", "PAM70"
};
if (_alphabet is DnaAlphabet)
{
if (!similarityMatrixDNA.Contains(similarityMatrix.Name))
{
if (fixSimilarityMatrixErrors)
{
SimilarityMatrix = bestSimilarityMatrix;
}
else
{
throw new ArgumentException("Inappropriate Similarity Matrix for DNA.");
}
}
}
else if (_alphabet is ProteinAlphabet)
{
if (!similarityMatrixProtein.Contains(similarityMatrix.Name))
{
if (fixSimilarityMatrixErrors)
{
SimilarityMatrix = bestSimilarityMatrix;
}
else
{
throw new ArgumentException("Inappropriate Similarity Matrix for Protein.");
}
}
}
else if (_alphabet is RnaAlphabet)
{
if (!similarityMatrixRNA.Contains(similarityMatrix.Name))
{
if (fixSimilarityMatrixErrors)
{
SimilarityMatrix = bestSimilarityMatrix;
}
else
{
throw new ArgumentException("Inappropriate Similarity Matrix for RNA.");
}
}
}
else
{
throw new ArgumentException("Invalid alphabet");
}
}
}
/// <summary>
/// Method which performs the alignment work.
/// </summary>
/// <param name="sequence1">First sequence</param>
/// <param name="sequence2">Second sequence</param>
/// <param name="useAffineGapModel">True to use affine gap model (separate open vs. extension cost)</param>
/// <returns></returns>
private IList <IPairwiseSequenceAlignment> DoAlign(ISequence sequence1, ISequence sequence2, bool useAffineGapModel)
{
usingAffineGapModel = useAffineGapModel;
if (sequence1 == null)
{
throw new ArgumentNullException("sequence1");
}
if (sequence2 == null)
{
throw new ArgumentNullException("sequence2");
}
if (!Alphabets.CheckIsFromSameBase(sequence1.Alphabet, sequence2.Alphabet))
{
Trace.Report(Properties.Resource.InputAlphabetsMismatch);
throw new ArgumentException(Properties.Resource.InputAlphabetsMismatch);
}
if (SimilarityMatrix == null)
{
Trace.Report(Properties.Resource.SimilarityMatrixCannotBeNull);
throw new ArgumentException(Properties.Resource.SimilarityMatrixCannotBeNull);
}
if (!SimilarityMatrix.ValidateSequence(sequence1))
{
Trace.Report(Properties.Resource.FirstInputSequenceMismatchSimilarityMatrix);
throw new ArgumentException(Properties.Resource.FirstInputSequenceMismatchSimilarityMatrix);
}
if (!SimilarityMatrix.ValidateSequence(sequence2))
{
Trace.Report(Properties.Resource.SecondInputSequenceMismatchSimilarityMatrix);
throw new ArgumentException(Properties.Resource.SecondInputSequenceMismatchSimilarityMatrix);
}
if (GapOpenCost > GapExtensionCost)
{
Trace.Report(Properties.Resource.GapOpenGreaterThanGapExtension);
throw new ArgumentException(Properties.Resource.GapOpenGreaterThanGapExtension);
}
_sequence1 = sequence1;
_sequence2 = sequence2;
_gap = Alphabets.CheckIsFromSameBase(Alphabets.Protein, sequence1.Alphabet) ? Alphabets.Protein.Gap : Alphabets.DNA.Gap;
ReferenceSequence = GetByteArrayFromSequence(_sequence1);
QuerySequence = GetByteArrayFromSequence(_sequence2);
// Assign consensus resolver if it was not assigned already.
IAlphabet alphabet = sequence1.Alphabet;
if (ConsensusResolver == null)
{
ConsensusResolver = new SimpleConsensusResolver(alphabet.HasAmbiguity ? alphabet : Alphabets.AmbiguousAlphabetMap[sequence1.Alphabet]);
}
else
{
ConsensusResolver.SequenceAlphabet = alphabet.HasAmbiguity ? alphabet : Alphabets.AmbiguousAlphabetMap[sequence1.Alphabet];
}
return(new List <IPairwiseSequenceAlignment> {
Process()
});
}
/// <summary>
/// For optimal graph formation, k-mer length should not be less
/// than half the length of the longest input sequence and
/// cannot be more than the length of the shortest input sequence.
/// Reference for estimating kmerlength from reads: Supplement material from
/// publication "ABySS: A parallel assembler for short read sequence data".
/// </summary>
/// <param name="sequences">List of input sequences.</param>
/// <returns>Estimated optimal kmer length.</returns>
public static int EstimateKmerLength(IEnumerable <ISequence> sequences)
{
// kmer length should be less than input sequence lengths
long minSeqLength = long.MaxValue;
long maxSeqLength = 0;
float maxLengthOfKmer = int.MaxValue;
float minLengthOfKmer = 0;
int kmerLength = 0;
if (sequences == null)
{
throw new ArgumentNullException("sequences");
}
if (!Alphabets.CheckIsFromSameBase(sequences.First().Alphabet, Alphabets.DNA))
{
throw new InvalidOperationException(Properties.Resource.CannotAssembleSequenceType);
}
foreach (ISequence seq in sequences)
{
long seqCount = seq.Count;
if (minSeqLength > seqCount)
{
// Get the min seq count to maxLength.
minSeqLength = seqCount;
}
if (maxSeqLength < seqCount)
{
// Get the max sequence count to minLength.
maxSeqLength = seqCount;
}
}
maxLengthOfKmer = minSeqLength;
// for optimal purpose, kmer length should be more than half of longest sequence
minLengthOfKmer = maxSeqLength / 2;
if (minLengthOfKmer < maxLengthOfKmer)
{
// Choose median value between the end-points
kmerLength = (int)Math.Ceiling((minLengthOfKmer + maxLengthOfKmer) / 2);
}
else
{
// In this case pick maxLength, since this is a hard limit
kmerLength = (int)Math.Floor(maxLengthOfKmer);
}
if (maxLengthOfKmer < kmerLength)
{
throw new InvalidOperationException(Properties.Resource.InappropriateKmerLength);
}
if (kmerLength <= 0)
{
throw new InvalidOperationException(Properties.Resource.KmerLength);
}
// This needs to be modified when we have a structure which can hold kmerData of more than 32 symbols.
return(kmerLength > 32 ? 32 : kmerLength);
}
/// <summary>
/// Main pregressive alignment algorithm aligns a set of sequences guided by
/// a binary tree.
/// </summary>
/// <param name="sequences">input sequences</param>
/// <param name="tree">a binary guide tree</param>
public void Align(IList <ISequence> sequences, BinaryGuideTree tree)
{
SequenceWeighting sequenceWeighting = null;
if (PAMSAMMultipleSequenceAligner.UseWeights)
{
sequenceWeighting = new SequenceWeighting(tree);
/*
* for (int i = 0; i < sequenceWeighting.Weights.Length; ++i)
* {
* sequenceWeighting.Weights[i] = 1;
* }
*/
}
if (sequences.Count == 0)
{
throw new ArgumentException("Empty set of sequences");
}
IAlphabet alphabet = sequences[0].Alphabet;
Parallel.For(1, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
if (!Alphabets.CheckIsFromSameBase(sequences[i].Alphabet, alphabet))
{
throw new ArgumentException("Inconsistent sequence alphabet");
}
});
if (PAMSAMMultipleSequenceAligner.UseWeights)
{
// Generate profile for leaf nodes
Parallel.For(0, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
tree.Nodes[i].ProfileAlignment = ProfileAlignment.GenerateProfileAlignment(sequences[i], sequenceWeighting.Weights[i]);
tree.Nodes[i].Weight = sequenceWeighting.Weights[i];
});
}
else
{
// Generate profile for leaf nodes
Parallel.For(0, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
tree.Nodes[i].ProfileAlignment = ProfileAlignment.GenerateProfileAlignment(sequences[i]);
});
}
// Iterate internal nodes;
// as defined in the tree, the last node is the root
for (int i = sequences.Count; i < tree.Nodes.Count; ++i)
{
if (tree.Nodes[i].NeedReAlignment)
{
// pull out its children
_nodeA = tree.Nodes[i].LeftChildren;
_nodeB = tree.Nodes[i].RightChildren;
if (PAMSAMMultipleSequenceAligner.UseWeights)
{
_profileAligner.Weights = new float[2];
_profileAligner.Weights[0] = _nodeA.Weight;
_profileAligner.Weights[1] = _nodeB.Weight;
tree.Nodes[i].Weight = _nodeA.Weight + _nodeB.Weight;
}
// align two profiles
ProfileAlignment result = null;
if (_nodeA.ProfileAlignment.NumberOfSequences < _nodeB.ProfileAlignment.NumberOfSequences)
{
result = (ProfileAlignment)_profileAligner.Align(
_nodeA.ProfileAlignment, _nodeB.ProfileAlignment);
// assign aligned profiles to the current internal node
tree.Nodes[i].ProfileAlignment = result;
// generate eString for the children nodes
_nodeA.EString = _profileAligner.GenerateEString(_profileAligner.AlignedA);
_nodeB.EString = _profileAligner.GenerateEString(_profileAligner.AlignedB);
}
else
{
result = (ProfileAlignment)_profileAligner.Align(
_nodeB.ProfileAlignment, _nodeA.ProfileAlignment);
// assign aligned profiles to the current internal node
tree.Nodes[i].ProfileAlignment = result;
// generate eString for the children nodes
_nodeA.EString = _profileAligner.GenerateEString(_profileAligner.AlignedB);
_nodeB.EString = _profileAligner.GenerateEString(_profileAligner.AlignedA);
}
// children node profiles can be deleted
_nodeA.ProfileAlignment.Clear();
_nodeB.ProfileAlignment.Clear();
}
}
// Convert original unaligned sequences to aligned ones by applying alignment paths in eStrings
try
{
_alignedSequences = new List <ISequence>(sequences.Count);
}
catch (OutOfMemoryException ex)
{
throw new Exception("Out of memory", ex.InnerException);
}
for (int i = 0; i < sequences.Count; ++i)
{
_alignedSequences.Add(null);
}
Parallel.For(0, sequences.Count, PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
ISequence seq = sequences[i];
BinaryGuideTreeNode node;
node = tree.Nodes[i];
while (!node.IsRoot)
{
seq = _profileAligner.GenerateSequenceFromEString(node.EString, seq);
node = node.Parent;
}
_alignedSequences[i] = seq;
});
}
