/// <summary>
/// Get the Cluster from given inputs of matches.
/// Steps are as follows:
/// 1. Sort MUMs based on query sequence start.
/// 2. Removing overlapping MUMs (in both sequences) and MUMs with same
/// diagonal offset (usually adjacent)
/// 3. Check for separation between two MUMs
/// 4. Check the diagonal separation
/// 5. If MUMs passes above conditions merge them in one cluster.
/// 6. Sort MUMs using cluster id
/// 7. Process clusters (Joining clusters)</summary>
/// <param name="matches">List of maximum unique matches</param>
/// <returns>List of Cluster</returns>
public IList <Cluster> BuildClusters(IList <MaxUniqueMatch> matches)
{
// Validate the input
if (null == matches)
{
return(null);
}
if (0 == matches.Count)
{
return(null);
}
IList <MaxUniqueMatchExtension> matchExtensions = new List <MaxUniqueMatchExtension>();
_unionFind = new List <int>();
// Convert list of matches to list of matchextensions
foreach (MaxUniqueMatch match in matches)
{
MaxUniqueMatchExtension matchExtension = new MaxUniqueMatchExtension(match);
_unionFind.Add(0);
matchExtensions.Add(matchExtension);
}
// Get the cluster and return it
return(GetClusters(matchExtensions));
}
/// <summary>
/// Create a new delta alignment
/// </summary>
/// <param name="referenceSequence">Reference sequence</param>
/// <param name="querySequence">Query sequence</param>
/// <param name="cluster">Cluster object</param>
/// <param name="match">Match object</param>
/// <returns>Newly created DeltaAlignment object</returns>
internal static DeltaAlignment NewAlignment(
ISequence referenceSequence,
ISequence querySequence,
Cluster cluster,
MaxUniqueMatchExtension match)
{
DeltaAlignment deltaAlignment = new DeltaAlignment(referenceSequence, querySequence);
deltaAlignment.FirstSequenceStart = match.FirstSequenceStart;
deltaAlignment.SecondSequenceStart = match.SecondSequenceStart;
deltaAlignment.FirstSequenceEnd = match.FirstSequenceStart
+ match.Length
- 1;
deltaAlignment.SecondSequenceEnd = match.SecondSequenceStart
+ match.Length
- 1;
deltaAlignment.QueryDirection = cluster.QueryDirection;
return(deltaAlignment);
}
/// <summary>
/// Find the longest increasing sub sequence from the given set of MUMs
/// </summary>
/// <param name="sortedMums">List of sorted MUMs</param>
/// <returns>Longest Increasing Subsequence</returns>
public IList <MaxUniqueMatch> GetLongestSequence(IList <MaxUniqueMatch> sortedMums)
{
MaxUniqueMatchExtension[] matches = ConvertToMUMExtension(sortedMums);
for (var counteri = 0; counteri < matches.Length; counteri++)
{
var matches_i = matches[counteri];
// Initialize the MUM Extension
matches_i.Score = matches[counteri].Length;
matches_i.WrapScore = matches[counteri].Length;
matches_i.Adjacent = 0;
matches_i.From = -1;
for (var counterj = 0; counterj < counteri; counterj++)
{
MaxUniqueMatchExtension matches_j = matches[counterj];
// Find the overlap in query sequence of MUM
var overlap2 = matches_j.SecondSequenceStart + matches_j.Length;
overlap2 -= matches_i.SecondSequenceStart;
var overlap = overlap2 > 0 ? overlap2 : 0;
// Calculate the score for query sequence of MUM
var score = matches_j.Score
+ matches_i.Length
- overlap;
if (score > matches_i.WrapScore)
{
matches_i.WrapScore = score;
}
// Find the overlap in reference sequence of MUM
var overlap1 = matches_j.FirstSequenceStart
+ matches_j.Length
- matches_i.FirstSequenceStart;
overlap = overlap > overlap1 ? overlap : overlap1;
score = matches_j.Score
+ matches_i.Length
- overlap;
if (score > matches_i.Score)
{
// To remove crosses, mark counteri as next MUM From counterj
// without any crosses
matches_i.From = counterj;
// Set the new score and overlap after removing the cross
matches_i.Score = score;
matches_i.Adjacent = overlap;
}
// Calculate the score for reference sequence of MUM
score = matches_j.WrapScore
+ matches_i.Length
- overlap;
if (score >= matches_i.WrapScore)
{
matches_i.WrapScore = score;
}
}
}
// Find the best longest increasing subsequence
// Sequence with highest score is the longest increasing subsequence
var best = 0;
var bestScore = matches[best].Score;
for (var counteri = 1; counteri < matches.Length; counteri++)
{
if (matches[counteri].Score > bestScore)
{
best = counteri;
bestScore = matches[best].Score;
}
}
// Mark the MUMs in longest increasing subsequence as "Good"
for (var counteri = best; counteri >= 0; counteri = matches[counteri].From)
{
matches[counteri].IsGood = true;
}
// Clear the list
// Perform the adjustment to the MUMs in longest increasing subsequence (remove over)
// Add it the list
sortedMums.Clear();
foreach (var t in matches)
{
if (t.IsGood)
{
var adjacent = t.Adjacent;
if (0 != adjacent)
{
t.FirstSequenceStart += adjacent;
t.SecondSequenceStart += adjacent;
t.Length -= adjacent;
}
if (0 < t.Length)
{
sortedMums.Add((MaxUniqueMatch)t);
}
}
}
// Return the list of MUMs that represent the longest increasing subsequence
return(sortedMums);
}
/// <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 IList <DeltaAlignment> ExtendClusters(Synteny synteny)
{
bool isClusterExtended = false;
IList <DeltaAlignment> deltaAlignments = new List <DeltaAlignment>();
DeltaAlignment deltaAlignment = null;
DeltaAlignment targetAlignment = null;
Cluster currentCluster = null;
Cluster targetCluster = synteny.Clusters.Last();
int targetReference;
int targetQuery;
int methodName = NUCmerAligner.ForwardAlignFlag;
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 (MaxUniqueMatchExtension match in currentCluster.Matches)
{
if (isClusterExtended)
{
if (deltaAlignment.FirstSequenceEnd != match.FirstSequenceStart ||
deltaAlignment.SecondSequenceEnd != match.SecondSequenceStart)
{
continue;
}
deltaAlignment.FirstSequenceEnd += match.Length - 1;
deltaAlignment.SecondSequenceEnd += match.Length - 1;
}
else
{
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
targetAlignment = GetPreviousAlignment(deltaAlignments, deltaAlignment);
if (ExtendToPreviousSequence(
synteny.ReferenceSequence,
synteny.QuerySequence,
deltaAlignments,
deltaAlignment,
targetAlignment))
{
deltaAlignment = targetAlignment;
}
}
methodName = NUCmerAligner.ForwardAlignFlag;
if (currentCluster.Matches.IndexOf(match) < currentCluster.Matches.Count - 1)
{
// extend till the match in the current cluster
MaxUniqueMatchExtension nextMatch =
currentCluster.Matches[currentCluster.Matches.IndexOf(match) + 1];
targetReference = nextMatch.FirstSequenceStart;
targetQuery = nextMatch.SecondSequenceStart;
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 |= NUCmerAligner.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);
}
