/// <summary>
/// Extend the cluster in synteny
/// </summary>
/// <param name="synteny">Synteny in which cluster needs to be extened.</param>
/// <returns>List of delta alignments</returns>
private List<DeltaAlignment> ExtendClusters(Synteny synteny)
{
bool isClusterExtended = false;
List<DeltaAlignment> deltaAlignments = new List<DeltaAlignment>();
DeltaAlignment deltaAlignment = null;
Cluster currentCluster;
Cluster targetCluster = synteny.Clusters.Last();
IList<Cluster> clusters = synteny.Clusters;
// Sort the cluster by first sequence start
clusters = SortCluster(clusters, FirstSequenceStart);
IEnumerator<Cluster> previousCluster = clusters.GetEnumerator();
previousCluster.MoveNext();
IEnumerator<Cluster> cluster = clusters.GetEnumerator();
while (cluster.MoveNext())
{
currentCluster = cluster.Current;
if (!isClusterExtended
&& (currentCluster.IsFused
|| IsClusterShadowed(deltaAlignments, currentCluster, deltaAlignment)))
{
currentCluster.IsFused = true;
previousCluster.MoveNext();
currentCluster = previousCluster.Current;
continue;
}
// Extend the match
foreach (MatchExtension match in currentCluster.Matches)
{
if (isClusterExtended)
{
if (deltaAlignment.FirstSequenceEnd != match.ReferenceSequenceOffset
|| deltaAlignment.SecondSequenceEnd != match.QuerySequenceOffset)
{
continue;
}
deltaAlignment.FirstSequenceEnd += match.Length - 1;
deltaAlignment.SecondSequenceEnd += match.Length - 1;
}
else
{
//TODO: Do we need sequence here? Changed to sequence id.
deltaAlignment = DeltaAlignment.NewAlignment(
synteny.ReferenceSequence,
synteny.QuerySequence,
currentCluster,
match);
deltaAlignments.Add(deltaAlignment);
// Find the MUM which is a good candidate for extension in reverse direction
DeltaAlignment targetAlignment = GetPreviousAlignment(deltaAlignments, deltaAlignment);
if (ExtendToPreviousSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignments,
deltaAlignment,
targetAlignment))
{
deltaAlignment = targetAlignment;
}
}
int methodName = ModifiedSmithWaterman.ForwardAlignFlag;
long targetReference;
long targetQuery;
if (currentCluster.Matches.IndexOf(match) < currentCluster.Matches.Count - 1)
{
// extend till the match in the current cluster
MatchExtension nextMatch =
currentCluster.Matches[currentCluster.Matches.IndexOf(match) + 1];
targetReference = nextMatch.ReferenceSequenceOffset;
targetQuery = nextMatch.QuerySequenceOffset;
isClusterExtended = ExtendToNextSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignment,
targetReference,
targetQuery,
methodName);
}
else
{
// extend till next cluster
targetReference = synteny.ReferenceSequence.Count - 1;
targetQuery = synteny.QuerySequence.Count() - 1;
targetCluster = GetNextCluster(
clusters,
currentCluster,
ref targetReference,
ref targetQuery);
if (!synteny.Clusters.Contains(targetCluster))
{
methodName |= ModifiedSmithWaterman.OptimalFlag;
}
isClusterExtended = ExtendToNextSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignment,
targetReference,
targetQuery,
methodName);
}
}
if (!synteny.Clusters.Contains(targetCluster))
{
isClusterExtended = false;
}
currentCluster.IsFused = true;
if (!isClusterExtended)
{
previousCluster.MoveNext();
currentCluster = previousCluster.Current;
}
else
{
currentCluster = targetCluster;
}
}
return deltaAlignments;
}
/// <summary>
/// Process the cluster
/// 1. Re-map the reference sequence index to original index
/// 2. Create synteny
/// 3. Process synteny
/// </summary>
/// <param name="clusters">List of clusters of a read.</param>
/// <returns>List of delta alignments</returns>
public IEnumerable<DeltaAlignment> ProcessCluster(IList<Cluster> clusters)
{
if (clusters == null)
{
throw new ArgumentNullException("clusters");
}
if (clusters.Count == 0)
{
return Enumerable.Empty<DeltaAlignment>();
}
bool isReverse = clusters.Any(c => c.IsReverseQueryDirection);
ISequence currentReference = null;
List<Synteny> syntenies = new List<Synteny>();
Synteny currentSynteny = null;
ISequence querySequence = null;
ISequence referenceSequence = null;
_nucmerAligner.SimilarityMatrix = SimilarityMatrix;
_nucmerAligner.BreakLength = BreakLength;
long referenceSequenceLength = _internalReferenceSequence.Count;
foreach (Cluster clusterIterator in clusters)
{
List<MatchExtension> clusterMatches;
if (null != currentSynteny)
{
// Remove the empty clusters (if any)
if ((0 < currentSynteny.Clusters.Count)
&& (0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
clusterMatches = new List<MatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches, isReverse));
}
foreach (MatchExtension matchIterator in clusterIterator.Matches)
{
ISequence currentQuery = matchIterator.Query;
if (matchIterator.ReferenceSequenceOffset < referenceSequenceLength)
{
currentReference = _internalReferenceSequence;
}
else
{
matchIterator.ReferenceSequenceOffset -= referenceSequenceLength + 1;
}
if ((null == referenceSequence)
|| (null == querySequence)
|| (string.Compare(referenceSequence.ID, currentReference.ID, StringComparison.OrdinalIgnoreCase) != 0)
|| string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) != 0)
{
bool found = false;
if ((null != querySequence)
&& (string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) == 0))
{
// Check if Synteny already exists
// If found, mark the synteny and break
foreach (Synteny syntenyIterator in syntenies)
{
if ((String.Compare(
syntenyIterator.ReferenceSequence.ID,
currentReference.ID,
StringComparison.OrdinalIgnoreCase) == 0)
&& (String.Compare(
syntenyIterator.QuerySequence.ID,
currentQuery.ID,
StringComparison.OrdinalIgnoreCase) == 0))
{
currentSynteny = syntenyIterator;
found = true;
break;
}
}
}
else
{
ProcessSynteny(syntenies);
}
referenceSequence = currentReference;
querySequence = currentQuery;
// Remove the empty clusters (if any)
if ((null != currentSynteny)
&& (0 < currentSynteny.Clusters.Count)
&& (0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
if (!found)
{
// Create a Synteny
currentSynteny = new Synteny(
currentReference,
currentQuery);
// Add a cluster to Synteny
syntenies.Add(currentSynteny);
}
clusterMatches = new List<MatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches, isReverse));
}
if (1 < matchIterator.Length)
{
currentSynteny.Clusters.Last().Matches.Add(matchIterator);
}
}
}
return ProcessSynteny(syntenies);
}
/// <summary>
/// Process the cluster
/// 1. Re-map the reference sequence index to original index
/// 2. Create synteny
/// 3. Process synteny
/// </summary>
/// <param name="clusters">List of clusters of a read.</param>
/// <returns>List of delta alignments</returns>
public IEnumerable <DeltaAlignment> ProcessCluster(IList <Cluster> clusters)
{
if (clusters == null)
{
throw new ArgumentNullException("clusters");
}
if (clusters.Count == 0)
{
return(Enumerable.Empty <DeltaAlignment>());
}
bool isReverse = clusters.Any(c => c.IsReverseQueryDirection);
ISequence currentReference = null;
List <Synteny> syntenies = new List <Synteny>();
Synteny currentSynteny = null;
ISequence querySequence = null;
ISequence referenceSequence = null;
_nucmerAligner.SimilarityMatrix = SimilarityMatrix;
_nucmerAligner.BreakLength = BreakLength;
long referenceSequenceLength = _internalReferenceSequence.Count;
foreach (Cluster clusterIterator in clusters)
{
List <MatchExtension> clusterMatches;
if (null != currentSynteny)
{
// Remove the empty clusters (if any)
if ((0 < currentSynteny.Clusters.Count) &&
(0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
clusterMatches = new List <MatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches, isReverse));
}
foreach (MatchExtension matchIterator in clusterIterator.Matches)
{
ISequence currentQuery = matchIterator.Query;
if (matchIterator.ReferenceSequenceOffset < referenceSequenceLength)
{
currentReference = _internalReferenceSequence;
}
else
{
matchIterator.ReferenceSequenceOffset -= referenceSequenceLength + 1;
}
if ((null == referenceSequence) ||
(null == querySequence) ||
(string.Compare(referenceSequence.ID, currentReference.ID, StringComparison.OrdinalIgnoreCase) != 0) ||
string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) != 0)
{
bool found = false;
if ((null != querySequence) &&
(string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) == 0))
{
// Check if Synteny already exists
// If found, mark the synteny and break
foreach (Synteny syntenyIterator in syntenies)
{
if ((String.Compare(
syntenyIterator.ReferenceSequence.ID,
currentReference.ID,
StringComparison.OrdinalIgnoreCase) == 0) &&
(String.Compare(
syntenyIterator.QuerySequence.ID,
currentQuery.ID,
StringComparison.OrdinalIgnoreCase) == 0))
{
currentSynteny = syntenyIterator;
found = true;
break;
}
}
}
else
{
ProcessSynteny(syntenies);
}
referenceSequence = currentReference;
querySequence = currentQuery;
// Remove the empty clusters (if any)
if ((null != currentSynteny) &&
(0 < currentSynteny.Clusters.Count) &&
(0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
if (!found)
{
// Create a Synteny
currentSynteny = new Synteny(
currentReference,
currentQuery);
// Add a cluster to Synteny
syntenies.Add(currentSynteny);
}
clusterMatches = new List <MatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches, isReverse));
}
if (1 < matchIterator.Length)
{
currentSynteny.Clusters.Last().Matches.Add(matchIterator);
}
}
}
return(ProcessSynteny(syntenies));
}
/// <summary>
/// Extend the cluster in synteny
/// </summary>
/// <param name="synteny">Synteny in which cluster needs to be extened.</param>
/// <returns>List of delta alignments</returns>
private List <DeltaAlignment> ExtendClusters(Synteny synteny)
{
bool isClusterExtended = false;
List <DeltaAlignment> deltaAlignments = new List <DeltaAlignment>();
DeltaAlignment deltaAlignment = null;
Cluster currentCluster;
IList <Cluster> clusters = synteny.Clusters;
// Sort the cluster by first sequence start
clusters = SortCluster(clusters, FirstSequenceStart);
Cluster targetCluster = synteny.Clusters.Last();
IEnumerator <Cluster> previousCluster = clusters.GetEnumerator();
previousCluster.MoveNext();
IEnumerator <Cluster> cluster = clusters.GetEnumerator();
while (cluster.MoveNext())
{
currentCluster = cluster.Current;
if (!isClusterExtended &&
(currentCluster.IsFused ||
IsClusterShadowed(deltaAlignments, currentCluster, deltaAlignment)))
{
currentCluster.IsFused = true;
previousCluster.MoveNext();
currentCluster = previousCluster.Current;
continue;
}
// Extend the match
foreach (MatchExtension match in currentCluster.Matches)
{
if (isClusterExtended)
{
if (deltaAlignment.FirstSequenceEnd != match.ReferenceSequenceOffset ||
deltaAlignment.SecondSequenceEnd != match.QuerySequenceOffset)
{
continue;
}
deltaAlignment.FirstSequenceEnd += match.Length - 1;
deltaAlignment.SecondSequenceEnd += match.Length - 1;
}
else
{
//TODO: Do we need sequence here? Changed to sequence id.
deltaAlignment = DeltaAlignment.NewAlignment(
synteny.ReferenceSequence,
synteny.QuerySequence,
currentCluster,
match);
deltaAlignments.Add(deltaAlignment);
// Find the MUM which is a good candidate for extension in reverse direction
DeltaAlignment targetAlignment = GetPreviousAlignment(deltaAlignments, deltaAlignment);
if (targetAlignment != deltaAlignment &&
//TODO: NEED TO VERIFY THIS!!!
//if (
ExtendToPreviousSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignments,
deltaAlignment,
targetAlignment))
{
deltaAlignment = targetAlignment;
}
}
int methodName = ModifiedSmithWaterman.ForwardAlignFlag;
long targetReference;
long targetQuery;
if (currentCluster.Matches.IndexOf(match) < currentCluster.Matches.Count - 1)
{
// extend till the match in the current cluster
MatchExtension nextMatch =
currentCluster.Matches[currentCluster.Matches.IndexOf(match) + 1];
targetReference = nextMatch.ReferenceSequenceOffset;
targetQuery = nextMatch.QuerySequenceOffset;
isClusterExtended = ExtendToNextSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignment,
targetReference,
targetQuery,
methodName);
}
else
{
// extend till next cluster
targetReference = synteny.ReferenceSequence.Count - 1;
targetQuery = synteny.QuerySequence.Count() - 1;
targetCluster = GetNextCluster(
clusters,
currentCluster,
ref targetReference,
ref targetQuery);
if (!synteny.Clusters.Contains(targetCluster))
{
methodName |= ModifiedSmithWaterman.OptimalFlag;
}
isClusterExtended = ExtendToNextSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignment,
targetReference,
targetQuery,
methodName);
}
}
if (!synteny.Clusters.Contains(targetCluster))
{
isClusterExtended = false;
}
currentCluster.IsFused = true;
if (!isClusterExtended)
{
previousCluster.MoveNext();
currentCluster = previousCluster.Current;
}
else
{
currentCluster = targetCluster;
}
}
return(deltaAlignments);
}
/// <summary>
/// Process the cluster
/// 1. Re-map the reference sequence index to original index
/// 2. Create synteny
/// 3. Process synteny
/// </summary>
/// <param name="referenceSequenceList">List of reference sequences</param>
/// <param name="clusters">List of clusters</param>
/// <returns>List of delta alignments</returns>
protected override IList <DeltaAlignment> ProcessCluster(
IList <ISequence> referenceSequenceList,
IList <Cluster> clusters)
{
ISequence currentReference = null;
ISequence currentQuery = null;
IList <Synteny> syntenies = new List <Synteny>();
IList <MaxUniqueMatchExtension> clusterMatches = null;
Synteny currentSynteny = null;
ISequence referenceSequence = null;
ISequence querySequence = null;
bool found = false;
nucmerAligner.SimilarityMatrix = SimilarityMatrix;
nucmerAligner.BreakLength = BreakLength;
foreach (Cluster clusterIterator in clusters)
{
if (null != currentSynteny)
{
// Remove the empty clusters (if any)
if ((null != currentSynteny) &&
(0 < currentSynteny.Clusters.Count) &&
(0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
clusterMatches = new List <MaxUniqueMatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches));
}
foreach (MaxUniqueMatchExtension matchIterator in clusterIterator.Matches)
{
currentQuery = matchIterator.Query;
// Re-map the reference coordinate back to its original sequence
foreach (ISequence sequence in referenceSequenceList)
{
if (matchIterator.FirstSequenceStart < sequence.Count)
{
currentReference = sequence;
break;
}
else
{
matchIterator.FirstSequenceStart -= sequence.Count + 1;
}
}
if ((null == referenceSequence) ||
(null == querySequence) ||
(string.Compare(referenceSequence.ID, currentReference.ID, StringComparison.OrdinalIgnoreCase) != 0) ||
string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) != 0)
{
found = false;
if ((null != querySequence) &&
(string.Compare(querySequence.ID, currentQuery.ID, StringComparison.OrdinalIgnoreCase) == 0))
{
// Check if Synteny already exists
// If found, mark the synteny and break
foreach (Synteny syntenyIterator in syntenies)
{
if ((String.Compare(
syntenyIterator.ReferenceSequence.ID,
currentReference.ID,
StringComparison.OrdinalIgnoreCase) == 0) &&
(String.Compare(
syntenyIterator.QuerySequence.ID,
currentQuery.ID,
StringComparison.OrdinalIgnoreCase) == 0))
{
currentSynteny = syntenyIterator;
found = true;
break;
}
}
}
else
{
ProcessSynteny(syntenies);
}
referenceSequence = currentReference;
querySequence = currentQuery;
// Remove the empty clusters (if any)
if ((null != currentSynteny) &&
(0 < currentSynteny.Clusters.Count) &&
(0 == currentSynteny.Clusters.Last().Matches.Count))
{
currentSynteny.Clusters.Remove(
currentSynteny.Clusters.Last());
}
if (!found)
{
// Create a Synteny
currentSynteny = new Synteny(
currentReference,
currentQuery);
// Add a cluster to Synteny
syntenies.Add(currentSynteny);
}
clusterMatches = new List <MaxUniqueMatchExtension>();
currentSynteny.Clusters.Add(new Cluster(clusterMatches));
}
if (1 < matchIterator.Length)
{
currentSynteny.Clusters.Last().Matches.Add(matchIterator);
}
}
}
return(ProcessSynteny(syntenies));
}
