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// ==========================================================================
// SeqAn - The Library for Sequence Analysis
// ==========================================================================
// Copyright (c) 2006-2026, Knut Reinert, FU Berlin
// All rights reserved.
//
// Redistribution and use in source and binary forms, with or without
// modification, are permitted provided that the following conditions are met:
//
// * Redistributions of source code must retain the above copyright
// notice, this list of conditions and the following disclaimer.
// * Redistributions in binary form must reproduce the above copyright
// notice, this list of conditions and the following disclaimer in the
// documentation and/or other materials provided with the distribution.
// * Neither the name of Knut Reinert or the FU Berlin nor the names of
// its contributors may be used to endorse or promote products derived
// from this software without specific prior written permission.
//
// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
// AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
// IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE
// ARE DISCLAIMED. IN NO EVENT SHALL KNUT REINERT OR THE FU BERLIN BE LIABLE
// FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL
// DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR
// SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER
// CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT
// LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY
// OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH
// DAMAGE.
//
// ==========================================================================
// Author: Manuel Holtgrewe <manuel.holtgrewe@fu-berlin.de>
// ==========================================================================
#ifndef INCLUDE_SEQAN_CONSENSUS_CONSENSUS_BUILDER_H_
#define INCLUDE_SEQAN_CONSENSUS_CONSENSUS_BUILDER_H_
#include <map>
#include <seqan/graph_types.h>
#include <seqan/store.h>
#include "consensus_alignment_options.h"
#include "overlapper.h"
namespace seqan2 {
// ============================================================================
// Forwards
// ============================================================================
// ============================================================================
// Tags, Classes, Enums
// ============================================================================
// --------------------------------------------------------------------------
// Class ConsensusBuilder_
// --------------------------------------------------------------------------
template <typename TFragmentStore>
class ConsensusBuilder_
{
public:
ConsensusBuilder_(ConsensusAlignmentOptions const & options) : options(options)
{}
void run(TFragmentStore & store, std::vector<OverlapInfo_> const & overlapInfos) const;
private:
// Glorified pair<unsigned, int> with more verbose name for readID and offset.
struct AlignmentTarget
{
AlignmentTarget() : readID((unsigned)-1), offset(0) {}
AlignmentTarget(unsigned readID, int offset) : readID(readID), offset(offset) {}
unsigned readID;
int offset;
};
// Glorified triple for overlap computation.
struct PositionedRead
{
PositionedRead() : beginPos(0), endPos(0), readID((unsigned)-1) {}
PositionedRead(int beginPos, int endPos, unsigned readID) :
beginPos(beginPos), endPos(endPos), readID(readID)
{}
int beginPos;
int endPos;
unsigned readID;
bool operator<(PositionedRead const & other) const
{
return (std::make_pair(std::make_pair(beginPos, endPos), readID) <
std::make_pair(std::make_pair(other.beginPos, other.endPos), other.readID));
}
};
// Shortcut for fragments.
typedef String<Fragment<> > TFragments;
// Compute pairwise overlaps for the reads of each contig in cg.
//
// In case that there are regions higher than options.startConsensusCompression, we add subsample these reads and
// write out an entry (other read id, offset) to use as a position marker in the resulting MSA.
void computeOverlaps(
TFragments & fragments,
String<int> & scores,
Graph<Undirected<double> > & distances,
TFragmentStore const & store,
std::vector<OverlapInfo_> const & overlapInfos) const;
// Configuration to use for consensus building.
ConsensusAlignmentOptions options;
};
template <typename TFragmentStore>
void ConsensusBuilder_<TFragmentStore>::computeOverlaps(
typename ConsensusBuilder_<TFragmentStore>::TFragments & fragments,
String<int> & scores,
Graph<Undirected<double> > & distances,
TFragmentStore const & store,
std::vector<OverlapInfo_> const & overlapInfos) const
{
// Configure overlapper, no limit in error rate or minimum length.
OverlapperOptions_ ovlOptions;
ovlOptions.logging = (options.verbosity >= 3);
ovlOptions.overlapErrorRate = options.overlapMaxErrorRate;
ovlOptions.overlapMinLength = options.overlapMinLength; // accept all overlaps
typedef typename Value<typename TFragmentStore::TReadSeqStore const>::Type TReadSeq;
Overlapper_<String<Fragment<> >, TReadSeq> overlapper(ovlOptions);
for (std::vector<OverlapInfo_>::const_iterator it = overlapInfos.begin(); it != overlapInfos.end(); ++it)
{
Overlap_ ovl;
TFragments frags;
if (overlapper.computeOverlap(ovl, frags, store.readSeqStore[it->seq0], store.readSeqStore[it->seq1],
OverlapCandidate_(it->seq0, it->seq1, it->pos1 - it->numErrors,
it->pos1 + it->numErrors)))
{
append(fragments, frags);
int ovlScore = ovl.length() - ovl.errors; // pseudo-score
resize(scores, length(fragments), ovlScore);
int quality = (ovl.length() > 0) ? (ovl.length() - ovl.errors) * 100 / ovl.length() : 0;
addEdge(distances, ovl.seq0, ovl.seq1, quality);
}
}
}
// ---------------------------------------------------------------------------
// Function alignmentGraphToSmoothFragmentStore()
// ---------------------------------------------------------------------------
// Note that this function relies on the "all mated, adjacent reads" assumption.
template <typename TFragmentStore, typename TSequence, typename TCargo, typename TSetSpec, typename TSpec>
bool alignmentGraphToFragmentStore(TFragmentStore & store,
Graph<Alignment<StringSet<TSequence, TSetSpec>, TCargo, TSpec> > const & g,
Graph<Undirected<double> > const & distances,
String<unsigned> const & component,
String<unsigned> const & order,
unsigned numComponents,
bool logging)
{
bool const DEBUG_INCONSISTENT_LEN = false;
// std::cerr << ">>>>>>>>>>>>\n<<<<<<<<<<<<<<<<\n";
// NOTE: seqToCluster is indexed by POSITION in the read set of g and not by the ID.
// TODO(holtgrew): This function is very similar to the updateStoreFromAlignmentGraph computeProfiles functions. Maybe we can share the commonality?
typedef Graph<Alignment<StringSet<TSequence, TSetSpec>, TCargo, TSpec> > TAlignmentGraph;
// -----------------------------------------------------------------------
// Get connected components of distances / read alignment clusters.
// -----------------------------------------------------------------------
// Each cluster corresponds to a contig.
// A cluster is a CC in the graph where each sequences is a vertex and two vertices are connected if they have an
// overlap alignment.
String<unsigned> seqToCluster;
if (logging)
std::cerr << "# vertices: " << numVertices(distances) << "\n"
<< "# edges: " << numEdges(distances) << "\n";
unsigned numClusters = connectedComponents(seqToCluster, distances);
if (logging)
std::cerr << "# clusters: " << numClusters << std::endl
<< "# components: " << numComponents << std::endl;
clear(store.contigStore);
resize(store.contigStore, numClusters);
String<unsigned> contigLengths;
resize(contigLengths, numClusters, 0);
for (unsigned i = 0; i < numClusters; ++i)
{
std::stringstream ss;
ss << "contig_" << i;
appendValue(store.contigNameStore, ss.str());
}
// -----------------------------------------------------------------------
// Visit components in topological order and generate profile sequences.
// -----------------------------------------------------------------------
// Get mapping from component to vertices.
String<String<unsigned> > componentVertices;
resize(componentVertices, numComponents);
typedef typename Iterator<TAlignmentGraph, VertexIterator>::Type TVertexIterator;
for (TVertexIterator itV(g); !atEnd(itV); goNext(itV))
appendValue(componentVertices[getProperty(component, *itV)], *itV);
// For each cluster, the currently overlapping reads.
std::vector<std::set<unsigned> > activeReads(numClusters);
std::vector<unsigned> gapCount(length(stringSet(g)), 0);
// Recreate alignedReadStore.
clear(store.alignedReadStore);
resize(store.alignedReadStore, length(store.readSeqStore));
// Iterate vertices in topological order.
for (typename Iterator<String<unsigned> const, Rooted>::Type it = begin(order, Rooted()); !atEnd(it); goNext(it))
{
unsigned c = *it; // Current component.
unsigned fLen = fragmentLength(g, front(componentVertices[c]));
for (unsigned i = 1; i < length(componentVertices[c]); ++i)
SEQAN_ASSERT_EQ(fragmentLength(g, front(componentVertices[c][0])),
fragmentLength(g, front(componentVertices[c][i])));
unsigned cl = seqToCluster[idToPosition(stringSet(g), sequenceId(g, front(componentVertices[c])))]; // Current cluster/contig.
// Update contig lengths.
unsigned from = contigLengths[cl];
contigLengths[cl] += fLen;
if (DEBUG_INCONSISTENT_LEN)
std::cerr << "==== c == " << c << "\n" << " from == " << from << "\n";
// The currently active reads that we see in this round. Required for inserting gaps below.
std::set<unsigned> seen;
std::set<unsigned> done;
// Insert gaps.
typedef typename Iterator<String<unsigned>, Rooted>::Type TDescIt;
for (TDescIt itV = begin(componentVertices[c], Rooted()); !atEnd(itV); goNext(itV))
{
unsigned idx = idToPosition(stringSet(g), sequenceId(g, *itV));
seen.insert(idx);
unsigned fBeg = fragmentBegin(g, *itV);
if (DEBUG_INCONSISTENT_LEN)
std::cerr << " fBeg of " << *itV << " is " << fBeg << " (idx == " << idx << ")\n";
// Register sequence as supporting in profile cl starting at position from in profile.
if (fBeg == 0u)
{
activeReads[cl].insert(idx);
store.alignedReadStore[idx].id = idx;
store.alignedReadStore[idx].readId = idx;
store.alignedReadStore[idx].contigId = cl;
store.alignedReadStore[idx].beginPos = from;
store.alignedReadStore[idx].endPos = from;
// store.alignedReadStore[idx].pairMatchId = idx / 2; // TODO(holtgrew): Set from read pair info.
if (DEBUG_INCONSISTENT_LEN)
{
std::cerr << "store.alignedReadStore[" << idx << "].beginPos == " << from << " | *itV == " << *itV << "\n";
std::cerr << "store.alignedReadStore[" << idx << "].endPos (= endPos) == " << from << "| *itV == " << *itV << "\n";
}
}
store.alignedReadStore[idx].endPos = from + fLen;
if (DEBUG_INCONSISTENT_LEN)
std::cerr << "store.alignedReadStore[" << idx << "].endPos = " << from << " + " << fLen << " == " << (from + fLen) << "| *itV == " << *itV << "\n";
unsigned fEnd = fBeg + fLen;
if (fEnd == length(stringSet(g)[idx]))
done.insert(idx);
}
// Get not seen reads.
typedef std::set<unsigned>::iterator TSetIt;
std::set<unsigned> notSeen;
for (TSetIt it = activeReads[cl].begin(); it != activeReads[cl].end(); ++it)
notSeen.insert(*it);
for (TSetIt it = seen.begin(); it != seen.end(); ++it)
notSeen.erase(*it);
// Insert gaps into these reads.
for (TSetIt itS = notSeen.begin(); itS != notSeen.end(); ++itS)
{
typedef typename TFragmentStore::TAlignedReadStore TAlignedReadStore;
typedef typename Value<TAlignedReadStore>::Type TAlignedRead;
typedef typename TAlignedRead::TGapAnchors TGapAnchors;
typedef typename TFragmentStore::TReadSeq TReadSeq;
SEQAN_ASSERT_NOT(empty(store.readSeqStore[*itS]));
Gaps<TReadSeq, AnchorGaps<TGapAnchors> > gaps(static_cast<TReadSeq>(store.readSeqStore[*itS]),
store.alignedReadStore[*itS].gaps);
insertGaps(gaps, from - store.alignedReadStore[*itS].beginPos, fLen);
store.alignedReadStore[*itS].endPos += fLen;
if (DEBUG_INCONSISTENT_LEN)
std::cerr << "store.alignedReadStore[" << *itS << "].endPos += " << fLen << " == " << store.alignedReadStore[*itS].endPos << "\n";
gapCount[*itS] += fLen;
if (DEBUG_INCONSISTENT_LEN)
std::cerr << "gapCount[" << *itS << "] == " << gapCount[*itS] << "\n";
}
// Deactive done reads.
for (TSetIt it = done.begin(); it != done.end(); ++it)
activeReads[cl].erase(*it);
}
// #if SEQAN_ENABLE_DEBUG
{
// Check for consistency.
typedef typename TFragmentStore::TAlignedReadStore TAlignedReadStore;
typedef typename Iterator<TAlignedReadStore, Standard>::Type TAlignedReadIter;
typedef typename TFragmentStore::TReadSeq TReadSeq;
TAlignedReadIter itEnd = end(store.alignedReadStore, Standard());
for (TAlignedReadIter it2 = begin(store.alignedReadStore, Standard()); it2 != itEnd; ++it2)
{
typedef Gaps<TReadSeq, AnchorGaps<String<typename TFragmentStore::TReadGapAnchor> > > TReadGaps;
TReadGaps readGaps(static_cast<TReadSeq>(store.readSeqStore[it2->readId]), it2->gaps);
SEQAN_ASSERT_EQ(length(readGaps) - length(store.readSeqStore[it2->readId]), gapCount[it2->readId]);
if (DEBUG_INCONSISTENT_LEN)
std::cerr << "READ GAPS\t" << (it2 - begin(store.alignedReadStore, Standard())) << "\t>>>" << readGaps << "<<< (" << length(readGaps) << ")\n"
<< " beginPos == " << it2->beginPos << ", endPos == " << it2->endPos << ", gapCount == " << gapCount[it2->readId] << "\n";
if ((unsigned)std::abs(it2->endPos - it2->beginPos) != length(readGaps))
{
SEQAN_FAIL("Inconsistent begin/endPos");
}
}
}
// #endif // #if SEQAN_ENABLE_DEBUG
return true;
}
template <typename TFragmentStore, typename TSequence, typename TCargo, typename TSetSpec, typename TSpec>
bool alignmentGraphToFragmentStore(TFragmentStore & store,
Graph<Alignment<StringSet<TSequence, TSetSpec>, TCargo, TSpec> > const & g,
Graph<Undirected<double> > const & distances,
bool logging)
{
typedef std::map<unsigned, unsigned> TComponentLength;
// -----------------------------------------------------------------------
// Compute connected components and get topological sorting of them.
// -----------------------------------------------------------------------
String<unsigned> component;
String<unsigned> order;
TComponentLength componentLength;
if (empty(g))
return true; // Nothing to do for empty graphs.
if (!convertAlignment(g, component, order, componentLength))
return false;
unsigned numComponents = length(order);
return alignmentGraphToFragmentStore(store, g, distances, component, order, numComponents, logging);
}
template <typename TFragmentStore>
void ConsensusBuilder_<TFragmentStore>::run(TFragmentStore & store,
std::vector<OverlapInfo_> const & overlapInfos) const
{
// The alignments as required by consensus MSA module.
TFragments fragments;
String<int> scores;
Graph<Undirected<double> > distances;
_resizeWithRespectToDistance(distances, length(store.readSeqStore));
// Obtain alignments according to contig graph.
computeOverlaps(fragments, scores, distances, store, overlapInfos);
// Build copy of dependent reads.
typedef typename Value<typename TFragmentStore::TReadSeqStore>::Type TReadSeq;
StringSet<TReadSeq> seqs;
for (unsigned i = 0; i < length(store.readSeqStore); ++i)
appendValue(seqs, store.readSeqStore[i]);
// Build the alignment graph.
Score<int, Simple> msaScoringScheme(2, -6, -4, -9); // TODO(holtgrew): Get from options!
typedef StringSet<TReadSeq, Dependent<> > TDepReadSet;
typedef Graph<Alignment<TDepReadSet, unsigned> > TInGraph;
TDepReadSet depSeqs(seqs);
TInGraph inGraph(depSeqs);
buildAlignmentGraph(fragments, scores, inGraph, msaScoringScheme, ReScore());
if (options.verbosity >= 2)
std::cerr << "Building alignment graph\n"
<< " # fragments: " << length(fragments) << "\n"
<< " # seqs: " << length(seqs) << "\n";
// Perform triplet library extension.
if (length(seqs) < 1000/*(unsigned)options.texStopCount*/) // TODO(holtgrew): Clean up.
tripletLibraryExtension(inGraph);
Graph<Tree<double> > guideTree;
Graph<Undirected<double> > dCopy(distances);
upgmaTree(dCopy, guideTree);
// Perform progressive alignment.
if (options.verbosity >= 2)
std::cerr << "progressive alignment...\n";
TInGraph graph(depSeqs);
assignStringSet(graph, stringSet(inGraph));
progressiveAlignment(inGraph, guideTree, graph);
// Build alignment graph.
if (options.verbosity >= 2)
std::cerr << "build AG..\n";
String<unsigned> component;
String<unsigned> order;
std::map<unsigned, unsigned> componentLength;
SEQAN_ASSERT_NOT(empty(graph));
bool b = convertAlignment(graph, component, order, componentLength);
(void) b;
SEQAN_ASSERT(b);
unsigned numComponents = length(order);
if (options.verbosity >= 2)
std::cerr << "AG\n"
<< " numVertices = " << numVertices(graph) << "\n"
<< " numEdges = " << numEdges(graph) << "\n"
<< " componentLength.size() = " << componentLength.size() << "\n"
<< " numComponents = " << numComponents << "\n";
if (options.verbosity >= 2)
std::cerr << "build store..\n";
alignmentGraphToFragmentStore(store, graph, distances, component, order, numComponents,
/*logging=*/(options.verbosity >= 3));
if (options.verbosity >= 2)
{
std::cerr << "CONSENSUS RESULT\n";
typedef typename Iterator<typename TFragmentStore::TAlignedReadStore, Standard>::Type TAlignedReadIter;
for (TAlignedReadIter it = begin(store.alignedReadStore, Standard()); it != end(store.alignedReadStore, Standard()); ++it)
std::cerr << "contigID=" << it->contigId
<< ", beginPos=" << std::min(it->beginPos, it->endPos)
<< ", readID=" << it->readId
<< ", seq=" << store.readSeqStore[it->readId]
<< "\n";
std::cerr << "\n";
}
if (options.verbosity >= 2)
{
std::cerr << "before realignment\n";
seqan2::AlignedReadLayout layout;
layoutAlignment(layout, store);
for (unsigned contigID = 0; contigID < length(store.contigStore); ++contigID)
{
int endPos = 0;
for (unsigned i = 0; i < length(store.alignedReadStore); ++i)
if (store.alignedReadStore[i].contigId == contigID)
endPos = std::max(endPos, (int)store.alignedReadStore[i].endPos);
std::cerr << ">contig_" << contigID << "\n";
printAlignment(std::cerr, layout, store, /*contigID=*/contigID, /*beginPos=*/0, /*endPos=*/endPos, 0, 30);
}
}
if (options.verbosity >= 2)
std::cerr << "realigning...\n";
for (unsigned i = 0; i < length(store.contigStore); ++i)
reAlignment(store, i, 1, 10, false);
if (options.verbosity >= 2)
{
std::cerr << "after realignment\n";
seqan2::AlignedReadLayout layout;
layoutAlignment(layout, store);
for (unsigned contigID = 0; contigID < length(store.contigStore); ++contigID)
{
int endPos = 0;
for (unsigned i = 0; i < length(store.alignedReadStore); ++i)
if (store.alignedReadStore[i].contigId == contigID)
endPos = std::max(endPos, (int)store.alignedReadStore[i].endPos);
std::cerr << ">contig_" << contigID << "\n";
printAlignment(std::cerr, layout, store, /*contigID=*/contigID, /*beginPos=*/0, /*endPos=*/endPos, 0, 30);
}
}
}
// ============================================================================
// Metafunctions
// ============================================================================
// ============================================================================
// Functions
// ============================================================================
} // namespace seqan2
#endif // #ifndef INCLUDE_SEQAN_CONSENSUS_CONSENSUS_BUILDER_H_
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