/// <summary>
/// Calculate sequence weights from the guide tree
/// </summary>
/// <param name="tree">a binary guide tree</param>
public SequenceWeighting(BinaryGuideTree tree)
{
_weights = new float[tree.NumberOfLeaves];
BinaryGuideTreeEdge _edge;
BinaryGuideTreeNode _node;
// Initialize: all weights are 0.
// Then sum up the weights from the leaf to the root
for (int i = 0; i < _weights.Length; ++i)
{
_weights[i] = 0;
_node = tree.Nodes[i];
while (!_node.IsRoot)
{
_edge = _node.ParentEdge;
_weights[i] += _edge.Length;
_node = _node.Parent;
}
}
// Normalize so that the average is 1.
float s = 0;
for (int i = 0; i < _weights.Length; ++i)
{
s += _weights[i];
}
for (int i = 0; i < _weights.Length; ++i)
{
_weights[i] = _weights[i] * _weights.Length / s;
_weights[i] = 1 / Weights[i];
}
}
/// <summary>
/// Compare two guide (sub)trees and mark the nodes that need to be re-aligned.
///
/// The algorithm traverses tree A in prefix order (children before parents),
/// assigning internal nodes ids N+1 through 2N-1 in the order visited. When visiting
/// an internal node, if any child node needs to be re-aligned, the node needs to
/// be re-aligned too. If the two children are both unmarked, and the two children nodes
/// are also having the same parent in tree B, this internal node does not need to be
/// re-aligned, and be assigned an ID the same as the parent node in tree B.
/// </summary>
/// <param name="treeA">binary guide (sub)tree</param>
/// <param name="treeB">binary guide (sub)tree</param>
public static void CompareTwoTrees(BinaryGuideTree treeA, BinaryGuideTree treeB)
{
if (treeA.NumberOfNodes != treeB.NumberOfNodes || treeA.NumberOfLeaves != treeB.NumberOfLeaves)
{
throw new ArgumentException("The two trees are not comparable");
}
Dictionary <int, int> nodeID2ListIndex = new Dictionary <int, int>(treeB.NumberOfNodes);
for (int i = 0; i < treeB.NumberOfNodes; ++i)
{
nodeID2ListIndex[treeB.Nodes[i].ID] = i;
}
BinaryGuideTreeNode node, nodeB;
for (int i = treeA.NumberOfLeaves; i < treeA.NumberOfNodes; ++i)
{
node = treeA.Nodes[i];
if (node.LeftChildren.NeedReAlignment == true || node.RightChildren.NeedReAlignment == true)
{
node.NeedReAlignment = true;
}
else
{
if (!nodeID2ListIndex.ContainsKey(node.LeftChildren.ID) || !nodeID2ListIndex.ContainsKey(node.RightChildren.ID))
{
node.NeedReAlignment = true;
}
else
{
nodeB = treeB.Nodes[nodeID2ListIndex[node.LeftChildren.ID]].Parent;
try
{
if (nodeB.LeftChildren.ID == node.RightChildren.ID || nodeB.RightChildren.ID == node.RightChildren.ID)
{
node.NeedReAlignment = false;
node.ID = nodeB.ID;
}
else
{
node.NeedReAlignment = true;
}
}
catch (NullReferenceException)
{
node.NeedReAlignment = true;
}
}
}
}
}
/// <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 (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;
});
}
/// <summary>
/// Cut a tree at an edge to generate 2 subtrees
/// </summary>
/// <param name="edgeIndex">zero-based edge index</param>
/// <returns>return[0] is the subtree with the same root as the original tree;
/// return[1] is the subtree rooted below the cutting edge</returns>
public BinaryGuideTree[] CutTree(int edgeIndex)
{
if (edgeIndex < 0 || edgeIndex >= _edges.Count)
{
throw new ArgumentException(string.Format("The edge ID provided when cutting the binary tree was not available. Given edge ID: {0}, available edges: {1}", edgeIndex, _edges.Count));
}
if (_edges[edgeIndex].ChildNode == null)
{
throw new Exception("The edge specified was not properly extended to a child node.Edge ID: " + edgeIndex);
}
_edges[edgeIndex].ChildNode.Parent = null;
if (_edges[edgeIndex].ParentNode.LeftChildren.ID == _edges[edgeIndex].ChildNode.ID)
{
_edges[edgeIndex].ParentNode.LeftChildren = null;
}
else
{
_edges[edgeIndex].ParentNode.RightChildren = null;
}
// generate two new trees
BinaryGuideTree treeA = new BinaryGuideTree(_root);
BinaryGuideTree treeB = new BinaryGuideTree(_edges[edgeIndex].ChildNode);
treeA.NumberOfNodes = _numberOfNodes;
treeB.NumberOfNodes = _numberOfNodes;
treeA.NumberOfLeaves = _numberOfLeaves;
treeB.NumberOfLeaves = _numberOfLeaves;
treeA.Nodes = _nodes;
treeA.Edges = _edges;
treeB.Nodes = _nodes;
treeB.Edges = _edges;
// pull the subtree nodes out for the two new roots
treeA.Nodes = (List <BinaryGuideTreeNode>)ExtractSubTreeNodes(treeA.Root);
treeB.Nodes = (List <BinaryGuideTreeNode>)ExtractSubTreeNodes(treeB.Root);
treeA.NumberOfNodes = treeA.Nodes.Count;
treeB.NumberOfNodes = treeB.Nodes.Count;
treeA.NumberOfLeaves = 0;
treeB.NumberOfLeaves = 0;
for (int i = 0; i < treeA.Nodes.Count; ++i)
{
if (treeA.Nodes[i].IsLeaf)
{
++treeA.NumberOfLeaves;
}
}
for (int i = 0; i < treeB.Nodes.Count; ++i)
{
if (treeB.Nodes[i].IsLeaf)
{
++treeB.NumberOfLeaves;
}
}
return(new BinaryGuideTree[2] {
treeA, treeB
});
}
/// <summary>
/// Performs Stage 1, 2, and 3 as described in class description.
/// </summary>
/// <param name="sequences">input unaligned sequences</param>
public IList <MBF.Algorithms.Alignment.ISequenceAlignment> Align(IList <ISequence> sequences)
{
// Initializations
if (sequences.Count > 0)
{
if (ConsensusResolver == null)
{
ConsensusResolver = new SimpleConsensusResolver(sequences[0].Alphabet);
}
else
{
ConsensusResolver.SequenceAlphabet = sequences[0].Alphabet;
}
}
// Get ProfileAligner ready
IProfileAligner profileAligner = null;
switch (_profileAlignerName)
{
case (ProfileAlignerNames.NeedlemanWunschProfileAligner):
if (_degreeOfParallelism == 1)
{
profileAligner = new NeedlemanWunschProfileAlignerSerial(
SimilarityMatrix, _profileProfileFunctionName, GapOpenCost, GapExtensionCost, _numberOfPartitions);
}
else
{
profileAligner = new NeedlemanWunschProfileAlignerParallel(
SimilarityMatrix, _profileProfileFunctionName, GapOpenCost, GapExtensionCost, _numberOfPartitions);
}
break;
case (ProfileAlignerNames.SmithWatermanProfileAligner):
if (_degreeOfParallelism == 1)
{
profileAligner = new SmithWatermanProfileAlignerSerial(
SimilarityMatrix, _profileProfileFunctionName, GapOpenCost, GapExtensionCost, _numberOfPartitions);
}
else
{
profileAligner = new SmithWatermanProfileAlignerParallel(
SimilarityMatrix, _profileProfileFunctionName, GapOpenCost, GapExtensionCost, _numberOfPartitions);
}
break;
default:
throw new ArgumentException("Invalid profile aligner name");
}
_alignedSequences = new List <ISequence>(sequences.Count);
float currentScore = 0;
// STAGE 1
Performance.Snapshot("Stage 1");
// Generate DistanceMatrix
KmerDistanceMatrixGenerator kmerDistanceMatrixGenerator =
new KmerDistanceMatrixGenerator(sequences, _kmerLength, _moleculeType, _distanceFunctionName);
// Hierarchical clustering
IHierarchicalClustering hierarcicalClustering =
new HierarchicalClusteringParallel
(kmerDistanceMatrixGenerator.DistanceMatrix, _hierarchicalClusteringMethodName);
// Generate Guide Tree
BinaryGuideTree binaryGuideTree =
new BinaryGuideTree(hierarcicalClustering);
// Progressive Alignment
IProgressiveAligner progressiveAlignerA = new ProgressiveAligner(profileAligner);
progressiveAlignerA.Align(sequences, binaryGuideTree);
currentScore = MsaUtils.MultipleAlignmentScoreFunction(progressiveAlignerA.AlignedSequences, SimilarityMatrix, GapOpenCost, GapExtensionCost);
if (currentScore > _alignmentScoreA)
{
_alignmentScoreA = currentScore;
_alignedSequencesA = progressiveAlignerA.AlignedSequences;
}
if (_alignmentScoreA > _alignmentScore)
{
_alignmentScore = _alignmentScoreA;
_alignedSequences = _alignedSequencesA;
}
if (PAMSAMMultipleSequenceAligner.FasterVersion)
{
_alignedSequencesB = _alignedSequencesA;
_alignedSequencesC = _alignedSequencesA;
_alignmentScoreB = _alignmentScoreA;
_alignmentScoreC = _alignmentScoreA;
}
else
{
BinaryGuideTree binaryGuideTreeB = null;
IHierarchicalClustering hierarcicalClusteringB = null;
KimuraDistanceMatrixGenerator kimuraDistanceMatrixGenerator = new KimuraDistanceMatrixGenerator();
if (PAMSAMMultipleSequenceAligner.UseStageB)
{
// STAGE 2
Performance.Snapshot("Stage 2");
// Generate DistanceMatrix from Multiple Sequence Alignment
int iterateTime = 0;
while (true)
{
++iterateTime;
kimuraDistanceMatrixGenerator.GenerateDistanceMatrix(_alignedSequences);
// Hierarchical clustering
hierarcicalClusteringB = new HierarchicalClusteringParallel
(kimuraDistanceMatrixGenerator.DistanceMatrix, _hierarchicalClusteringMethodName);
// Generate Guide Tree
binaryGuideTreeB = new BinaryGuideTree(hierarcicalClusteringB);
BinaryGuideTree.CompareTwoTrees(binaryGuideTreeB, binaryGuideTree);
binaryGuideTree = binaryGuideTreeB;
// Progressive Alignment
IProgressiveAligner progressiveAlignerB = new ProgressiveAligner(profileAligner);
progressiveAlignerB.Align(sequences, binaryGuideTreeB);
currentScore = MsaUtils.MultipleAlignmentScoreFunction(progressiveAlignerB.AlignedSequences, SimilarityMatrix, GapOpenCost, GapExtensionCost);
if (currentScore > _alignmentScoreB)
{
_alignmentScoreB = currentScore;
_alignedSequencesB = progressiveAlignerB.AlignedSequences;
break;
}
else
{
break;
}
}
if (_alignmentScoreB > _alignmentScore)
{
_alignmentScore = _alignmentScoreB;
_alignedSequences = _alignedSequencesB;
}
}
else
{
binaryGuideTreeB = binaryGuideTree;
}
// STAGE 3
Performance.Snapshot("Stage 3");
// refinement
//int maxRefineMentTime = sequences.Count * 2 - 2;
int maxRefineMentTime = 1;
if (sequences.Count == 2)
{
maxRefineMentTime = 0;
}
int refinementTime = 0;
_alignedSequencesC = new List <ISequence>(sequences.Count);
for (int i = 0; i < sequences.Count; ++i)
{
_alignedSequencesC.Add(new Sequence(_alphabet, _alignedSequences[i].ToString()));
}
List <int>[] leafNodeIndices = null;
List <int>[] allIndelPositions = null;
IProfileAlignment[] separatedProfileAlignments = null;
List <int>[] eStrings = null;
while (refinementTime < maxRefineMentTime)
{
++refinementTime;
Performance.Snapshot("Refinement iter " + refinementTime.ToString());
bool needRefinement = false;
for (int edgeIndex = 0; edgeIndex < binaryGuideTreeB.NumberOfEdges; ++edgeIndex)
{
leafNodeIndices = binaryGuideTreeB.SeparateSequencesByCuttingTree(edgeIndex);
allIndelPositions = new List <int> [2];
separatedProfileAlignments = ProfileAlignment.ProfileExtraction(_alignedSequencesC, leafNodeIndices[0], leafNodeIndices[1], out allIndelPositions);
eStrings = new List <int> [2];
if (separatedProfileAlignments[0].NumberOfSequences < separatedProfileAlignments[1].NumberOfSequences)
{
profileAligner.Align(separatedProfileAlignments[0], separatedProfileAlignments[1]);
eStrings[0] = profileAligner.GenerateEString(profileAligner.AlignedA);
eStrings[1] = profileAligner.GenerateEString(profileAligner.AlignedB);
}
else
{
profileAligner.Align(separatedProfileAlignments[1], separatedProfileAlignments[0]);
eStrings[0] = profileAligner.GenerateEString(profileAligner.AlignedB);
eStrings[1] = profileAligner.GenerateEString(profileAligner.AlignedA);
}
for (int set = 0; set < 2; ++set)
{
Parallel.ForEach(leafNodeIndices[set], PAMSAMMultipleSequenceAligner.parallelOption, i =>
{
Sequence seq = new Sequence(_alphabet, "");
seq.IsReadOnly = false;
int indexAllIndel = 0;
for (int j = 0; j < _alignedSequencesC[i].Count; ++j)
{
if (indexAllIndel < allIndelPositions[set].Count && j == allIndelPositions[set][indexAllIndel])
{
++indexAllIndel;
}
else
{
seq.Add(_alignedSequencesC[i][j]);
}
}
seq = profileAligner.GenerateSequenceFromEString(eStrings[set], seq);
seq.IsReadOnly = true;
_alignedSequencesC[i] = seq;
});
}
currentScore = MsaUtils.MultipleAlignmentScoreFunction(_alignedSequencesC, SimilarityMatrix, GapOpenCost, GapExtensionCost);
if (currentScore > _alignmentScoreC)
{
_alignmentScoreC = currentScore;
needRefinement = true;
// recreate the tree
kimuraDistanceMatrixGenerator.GenerateDistanceMatrix(_alignedSequencesC);
hierarcicalClusteringB = new HierarchicalClusteringParallel
(kimuraDistanceMatrixGenerator.DistanceMatrix, _hierarchicalClusteringMethodName);
binaryGuideTreeB = new BinaryGuideTree(hierarcicalClusteringB);
break;
}
}
if (!needRefinement)
{
refinementTime = maxRefineMentTime;
break;
}
}
if (_alignmentScoreC > _alignmentScore)
{
_alignmentScore = _alignmentScoreC;
_alignedSequences = _alignedSequencesC;
}
Performance.Snapshot("Stop Stage 3");
}
//just for the purpose of integrating PW and MSA with the same output
IList <MBF.Algorithms.Alignment.ISequenceAlignment> results = new List <MBF.Algorithms.Alignment.ISequenceAlignment>();
return(results);
}
