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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: Tobias Rausch <rausch@embl.de>
// Author: Anne-Katrin Emde <anne-katrin.emde@fu-berlin.de>
// ==========================================================================
#ifndef SEQAN_INCLUDE_SEQAN_GRAPH_ALGORITHM_REFINE_EXACT_H_
#define SEQAN_INCLUDE_SEQAN_GRAPH_ALGORITHM_REFINE_EXACT_H_
namespace seqan2 {
struct TagExactRefinement_;
typedef Tag<TagExactRefinement_> const ExactRefinement;
//exact method, every cut is made (unless it already exists)
template<typename TValue, typename TValue2, typename TSize>
inline bool
_cutIsValid(String<std::set<TValue> > & all_nodes,
TValue2 seq_i_pos,
TSize,
typename std::set<TValue>::iterator iter,
TSize,
Tag<TagExactRefinement_> const)
{
//cut already exists
if(iter != all_nodes[seq_i_pos].end())
return false;
return true;
}
template<typename TSize, typename TSpec,typename TPos>
inline void
_updateCutPosition(Fragment<TSize, ExactReversableFragment<TSpec> > & f, TPos & pos_j)
{
if(f.reversed)
++pos_j;
}
//template<typename TSize, typename TSpec,typename TPos>
//inline void
//_updateCutPosition(Fragment<TSize, ExactReversableFragment<TSpec> > const& f, TPos & pos_j)
//{
// if(f.reversed)
// ++pos_j;
//}
template<typename TFrag,typename TPos>
inline void
_updateCutPosition(TFrag &, TPos &)
{
return;
}
///////////////////////////////////////////////////////////////////////////////////////////////////////
//Recursive Refinement
//refine position node_i on sequence seq_i
template<typename TValue, typename TAlignmentString, typename TStringSet,typename TGraph, typename TPropertyMap,typename TSeqMap, typename TTagSpec>
inline void
_refine(TValue node_i,
TValue seq_i_id,
TStringSet & seqs,
TSeqMap & seq_map,
TAlignmentString & alis,
String<TGraph> & gs,
String<TPropertyMap> & pms,
String<std::set<TValue> > & all_nodes,
TValue min_len,
Tag<TTagSpec> tag)
{
typedef typename Cargo<typename Value<TPropertyMap>::Type>::Type TAlignmentPointer;
typedef typename Iterator<String<TAlignmentPointer>, Rooted>::Type TSegmentIterator;
//find all segment matches that contain the current position (node_i)
String<TAlignmentPointer> relevant_segments;
TValue seq_i_pos = idToPosition(seqs,seq_i_id);
findIntervalsExcludeTouching(relevant_segments, gs[seq_i_pos],pms[seq_i_pos],node_i);
TSegmentIterator segment_it = begin(relevant_segments);
TSegmentIterator segment_end = end(relevant_segments);
//foreach of those segments
while(segment_it != segment_end)
{
TValue match_id = (*segment_it).i1;
TValue seg_num = (*segment_it).i2; // first or second segment in seg match
//get the sequence that node_i needs to be projected onto (seq_j)
//and get the projected position (pos_j)
TValue seq_j_id, node_j;
_getOtherSequenceAndProject(alis[match_id],seg_num,seq_map,seq_i_id,node_i,seq_j_id,node_j);
TValue seq_j_pos = idToPosition(seqs,seq_j_id);
_updateCutPosition(alis[match_id],node_j);
typename std::set<TValue>::iterator iter;
iter = all_nodes[seq_j_pos].find(node_j);
//if node does not exist yet ---> insert and continue cutting
if(_cutIsValid(all_nodes,seq_j_pos,node_j,iter,min_len,tag))
{
all_nodes[seq_j_pos].insert(node_j);
_refine(node_j,seq_j_id,seqs,seq_map,alis,gs,pms,all_nodes,min_len,tag);
//TODO: else //verschmelzen, abschneiden und �bergehen, erst sp�ter...
//do nothing or resolve problems
}
++segment_it;
}
}
///////////////////////////////////////////////////////////////////////////////////////////////////////
//Construct interval trees
////////////////////////////////////////////////////////////////////////////////////////////////////
//construct intervals from allignments for each sequence (other Alignment types)
template<typename TInterval, typename TStringSet, typename TAlignmentString, typename TSeqMap>
void
_buildIntervalsForAllSequences(TAlignmentString & alis,
String<String<TInterval> > & intervals,
TStringSet & seqs,
TSeqMap & seq_map)
{
typedef typename Value<TInterval>::Type TValue;
typedef typename Cargo<TInterval>::Type TCargo;
typedef typename Iterator<TAlignmentString,Standard>::Type TAliIterator;
TAliIterator ali_it = begin(alis,Standard());
TAliIterator ali_end = end(alis,Standard());
TValue ali_counter = 0;
//foreach alignment
while(ali_it != ali_end)
{
TValue seq_i_id,begin_,end_;
//get the first sequence (and its begin and end) that takes part in the alignment (seq_i)
_getSeqBeginAndEnd(*ali_it,seq_map,seq_i_id,begin_,end_,0);
TValue seq_i_pos = idToPosition(seqs, seq_i_id);
//and append the interval (ali_begin, ali_end) with cargo ali* to the list of intervals of seq_i
appendValue(intervals[seq_i_pos],IntervalAndCargo<TValue,TCargo>(begin_,end_,TCargo(ali_counter,0)));
//get the second sequence (and its begin and end) that takes part in the alignment (seq_i)
_getSeqBeginAndEnd(*ali_it,seq_map,seq_i_id,begin_,end_,1);
seq_i_pos = idToPosition(seqs, seq_i_id);
//and again append the interval (ali_begin, ali_end) with cargo ali* to the list of intervals of seq_i
appendValue(intervals[seq_i_pos],IntervalAndCargo<TValue,TCargo>(begin_,end_,TCargo(ali_counter,1)));
++ali_counter;
++ali_it;
}
}
//get all intervals from the alignments and construct an interval tree for each sequence
template<typename TGraph, typename TPropertyMap, typename TAlignmentString, typename TSequence, typename TSetSpec, typename TValue, typename TSeqMap>
void
_createTreesForAllSequences(String<TGraph> & gs,
String<TPropertyMap> & pms,
TAlignmentString & alis,
StringSet<TSequence,TSetSpec> & seqs,
TSeqMap & seq_map,
TValue numSequences)
{
typedef typename Value<TAlignmentString>::Type TAlignment;
// typedef TValue TCargo;
typedef Pair<unsigned,unsigned,BitPacked<31,1> > TCargo;
typedef IntervalAndCargo<int,TCargo> TInterval;
typedef typename VertexDescriptor<TGraph>::Type TVertexDescriptor;
//std::cout <<"create interval trees...";
clock_t start, finish1;
double duration;
start = clock();
//one tree for each sequence
resize(gs,numSequences);
resize(pms,numSequences);
//and one string of intervals for each sequence
String<String<TInterval> > intervals;
resize(intervals,numSequences);
//fill intervals
_buildIntervalsForAllSequences(alis,intervals,seqs,seq_map);
TValue i = 0;
while(i < numSequences)
{
//std::cout << (numSequences-i) <<" more ("<<length(intervals[i])<<" intervals)... "<<std::flush;
//vllt zum speicher sparen: numSequences mal alle alis durchgehen
//und jedes mal nur buildIntervalsForJustOneSequence();
TValue center = length(seqs[i])/2; // center raus, hat hier nix zu suchen
//create interval tree!
createIntervalTree(gs[i],pms[i],intervals[i],center);
//intervals for sequence i are not needed anymore
clear(intervals[i]);
++i;
}
finish1 = clock();
duration = (double)(finish1 - start) / CLOCKS_PER_SEC;
//std::cout << "\ntook " << duration << " seconds.\n";
}
//step 1 of constructing the refined alignment graph: create all the nodes
template<typename TStringSet,typename TValue,typename TAliGraph>
void
_makeRefinedGraphNodes(String<std::set<TValue> > & all_nodes,
TStringSet & seqs,
TAliGraph & ali_g)
{
typedef typename std::set<TValue>::iterator TSetIterator;
//for each sequence look at all cut positions and create nodes between them
for(unsigned int seq_i_pos = 0; seq_i_pos < length(seqs); ++seq_i_pos)
{
TValue seq_i_id = positionToId(stringSet(ali_g), seq_i_pos);
TSetIterator it = all_nodes[seq_i_pos].begin();
TSetIterator end_it = all_nodes[seq_i_pos].end();
TSetIterator next_it = it;
if(next_it != end_it)
++next_it;
else
addVertex(ali_g, seq_i_id, 0, length(seqs[seq_i_pos]));
//first unaligned node
if(it != end_it && *it != 0)
addVertex(ali_g, seq_i_id, 0, *it);
//a new node for each interval
while(next_it != end_it)
{
TValue pos_i = *it;
addVertex(ali_g, seq_i_id, pos_i, *next_it - pos_i);
++it;
++next_it;
}
//last unaligned node
if(it !=end_it && *it<length(seqs[seq_i_pos]))
addVertex(ali_g, seq_i_id, *it, (length(seqs[seq_i_pos])) - *it);
all_nodes[seq_i_pos].clear();
}
}
//step 2 of constructing the refined alignment graph: add all edges
//version for exact refinement
template<typename TAlignmentString,typename TStringSet,typename TSeqMap, typename TPropertyMap,typename TScore,typename TAliGraph>
void
_makeRefinedGraphEdges(TAlignmentString & alis,
TPropertyMap & pm,
TStringSet & seqs,
TSeqMap & seq_map,
TScore & score_type,
TAliGraph & ali_g,
Tag<TagExactRefinement_> const)
{
typedef typename Value<TAlignmentString>::Type TAlign;
typedef typename Size<TAlign>::Type TValue;
typedef typename Iterator<TAlignmentString, Rooted>::Type TAliIterator;
typedef typename VertexDescriptor<TAliGraph>::Type TVertexDescriptor;
typedef typename EdgeDescriptor<TAliGraph>::Type TEdgeDescriptor;
typedef typename Cargo<TAliGraph>::Type TCargo;
//make edges
TAliIterator ali_it = begin(alis);
TAliIterator ali_end = end(alis);
//for each segment/fragment/alignment
while(ali_it != ali_end)
{
//get sequence, begin position and end position
TValue seq_id,begin_pos,end_pos;
_getSeqBeginAndEnd(*ali_it,seq_map,seq_id,begin_pos,end_pos,(TValue)0);
//get the node represents the current interval (begin_pos until next_cut_pos or end_pos)
TVertexDescriptor act_knot = findVertex(ali_g,seq_id,begin_pos);
TValue act_pos = begin_pos;
//for each interval that lies within the current segment/fragement/alignment
while(act_pos < end_pos)
{
//get other sequence and projected position
TValue seq_j_id,pos_j;
_getOtherSequenceAndProject(*ali_it,(TValue)0,seq_map,seq_id,act_pos,seq_j_id,pos_j);
//find node that contains the projected position (pos_j)
TVertexDescriptor vd = findVertex(ali_g, seq_j_id, pos_j);
SEQAN_ASSERT(fragmentBegin(ali_g,vd)==pos_j);
typename Value<TScore>::Type score = _getRefinedMatchScore(score_type,seqs,*ali_it,act_pos,pos_j,fragmentLength(ali_g,act_knot),fragmentLength(ali_g,vd));//,fragmentLength(ali_g,vd));
// typename Value<TScore>::Type score = fragmentLength(ali_g,vd);
score *= _getRefinedAnnoScore(ali_g,pm,vd,act_knot,score_type);
//this needs to be generalized (makes sense for positive scores only)
if(score <= 0) score = 1;
if(score > 0)
{
if (findEdge(ali_g, act_knot, vd) == 0) addEdge(ali_g,act_knot,vd,(TCargo)score);
else {
TEdgeDescriptor ed = findEdge(ali_g, act_knot, vd);
//if((TCargo)score > getCargo(ed))
//assignCargo(ed, score);
assignCargo(ed, getCargo(ed)+score);
}
}
//prepare for next interval
act_pos += fragmentLength(ali_g,act_knot);
act_knot = findVertex(ali_g,seq_id,act_pos);
}
++ali_it;
}
}
////////////////////////////////////////////////////////////////////////////////////////
//build refined alignment graph
////////////////////////////////////////////////////////////////////////////////////////
//nodes are numbered ascendingly:
//seq1 0 1 2 3 4
//seq2 5 6 7 8 9 10
//seq3 11 12 13 14 15
template<typename TValue,typename TAlignmentString,typename TScore,typename TSequence, typename TSetSpec,typename TAliGraph,typename TSeqMap,typename TTagSpec>
void
_makeAlignmentGraphFromRefinedSegments(String<std::set<TValue> > & all_nodes,
TAlignmentString & alis,
TScore & score_type,
StringSet<TSequence, TSetSpec> & seqs,
TSeqMap & seq_map,
TAliGraph & ali_g,
Tag<TTagSpec> const tag,
bool)
{
//std::cout << "making refined alignment graph...";
//clock_t start, finish1;
//double duration;
//start = clock();
//make nodes (same function for inexact and exact refinement)
_makeRefinedGraphNodes(all_nodes,seqs,ali_g);
bool pm = false;
//add edges (different functions depending on exact/inexact refinement)
_makeRefinedGraphEdges(alis,pm,seqs,seq_map,score_type,ali_g,tag);
//std::cout << "check\n";
//finish1 = clock();
//duration = (double)(finish1 - start) / CLOCKS_PER_SEC;
//std::cout << "\ntook " << duration << " seconds.\n";
}
template<typename TValue,typename TAlignmentString,typename TScore,typename TSequence, typename TSetSpec,typename TAliGraph,typename TSeqMap,typename TAnnoString,typename TTagSpec>
void
_makeAlignmentGraphFromRefinedSegments(String<std::set<TValue> > & all_nodes,
TAlignmentString & alis,
TScore & score_type,
StringSet<TSequence, TSetSpec> & seqs,
TSeqMap & seq_map,
TAliGraph & ali_g,
Tag<TTagSpec> const tag,
TAnnoString & annotation)
{
//std::cout << "making refined alignment graph...";
//clock_t start, finish1;
//double duration;
//start = clock();
//make nodes (same function for inexact and exact refinement)
_makeRefinedGraphNodes(all_nodes,seqs,ali_g);
//add annotation to nodes
typedef typename Value<TAnnoString>::Type TAnnotation;
//typedef typename Value<TAnnotation>::Type TLabel;
typedef char TLabel;
String<String<TLabel> > pm;
_addNodeAnnotation(seqs,seq_map,annotation,pm,ali_g,tag);
//add edges (different functions depending on exact/inexact refinement)
_makeRefinedGraphEdges(alis,pm,seqs,seq_map,score_type,ali_g,tag);
//std::cout << "check\n";
//finish1 = clock();
//duration = (double)(finish1 - start) / CLOCKS_PER_SEC;
//std::cout << "\ntook " << duration << " seconds.\n";
}
////////////////////////////////////////////////////////////////////////////////////////
//The big matchRefinement function that does everything: build interval trees, do the
//refinement and construct a refined alignment graph
////////////////////////////////////////////////////////////////////////////////////////
template<typename TAlignmentString, typename TAnnotation, typename TOutGraph, typename TSequence, typename TSetSpec, typename TScore,typename TTagSpec>
void
matchRefinement(TAlignmentString & alis,
StringSet<TSequence, TSetSpec> & seq,
TScore & score_type,
TOutGraph & ali_graph,
typename Size<typename Value<TAlignmentString>::Type>::Type min_fragment_len,
TAnnotation & annotation,
Tag<TTagSpec> const tag)
{
////////////////////////////////////////////////////////////////
//typedefs
typedef typename Value<TAlignmentString>::Type TAlign;
typedef typename Iterator<TAlignmentString, Rooted>::Type TAliIterator;
typedef typename Size<TAlign>::Type TValue;
// typedef TValue TCargo;
typedef Pair<unsigned,unsigned,BitPacked<31,1> > TCargo;
typedef IntervalAndCargo<int,TCargo> TInterval;
typedef Graph<Directed<void,WithoutEdgeId> > TGraph;
typedef IntervalTreeNode<TInterval> TNode;
typedef String<TNode> TPropertyMap;
typedef VertexDescriptor<TGraph>::Type TVertexDescriptor;
typedef String<TCargo> TList;
typedef typename std::set<TValue>::iterator TSetIterator;
////////////////////////////////////////////////////////////////
TValue numSequences = length(seq);
//weird ID --> good ID map
std::map<const void * ,int> seq_map;
for(int i = 0; i < (int) numSequences; ++i)
seq_map[getObjectId(seq[i])] = i;
////////////////////////////////////////////////////////////////
//build interval trees
String<TGraph> gs;
String<TPropertyMap> pms;
_createTreesForAllSequences(gs, pms, alis, seq, seq_map, numSequences);
////////////////////////////////////////////////////////////////
//do refinement
//std::cout <<"refining..."<<std::flush;
clock_t start, finish1;
double duration;
start = clock();
//all_nodes = set of all cut positions
String<std::set<TValue> > all_nodes;
resize(all_nodes,numSequences);
//call function _refine for each startknoten
TAliIterator ali_it = begin(alis);
TAliIterator ali_end = end(alis);
//for each segment/fragement/alignment
while(ali_it != ali_end)
{
//for each of the two sequences
for(TValue i = 0; i < 2; ++i)
{
TValue seq_i_id,begin_i,end_i;
_getSeqBeginAndEnd(*ali_it,seq_map,seq_i_id,begin_i,end_i,i);
TValue seq_i_pos = idToPosition(seq,seq_i_id);
//refine begin
TSetIterator iter = all_nodes[seq_i_pos].find(begin_i);
if(_cutIsValid(all_nodes,seq_i_pos,begin_i,iter,min_fragment_len,tag))
{
all_nodes[seq_i_pos].insert(begin_i);
_refine(begin_i, seq_i_id, seq, seq_map, alis, gs,pms,all_nodes,min_fragment_len,tag);//TStop());
}
//and end position
iter = all_nodes[seq_i_pos].find(end_i);
if(_cutIsValid(all_nodes,seq_i_pos,end_i,iter,(TValue) min_fragment_len,tag))
{
all_nodes[seq_i_pos].insert(end_i);
_refine(end_i, seq_i_id, seq, seq_map, alis, gs,pms,all_nodes, min_fragment_len,tag);//TStop());
}
}
++ali_it;
}
_addAnnotationCuts(all_nodes,alis,gs,pms,seq,seq_map,annotation,min_fragment_len,tag);
finish1 = clock();
duration = (double)(finish1 - start) / CLOCKS_PER_SEC;
//std::cout << "\ntook " << duration << " seconds.\n";
//for(int seq_i = 0; seq_i < length(seq); ++seq_i)
//{
// typename std::set<TValue>::iterator it = all_nodes[seq_i].begin();
// typename std::set<TValue>::iterator end_it = all_nodes[seq_i].end();
//
// while(it != end_it)
// {
// std::cout << *it << ",";
// ++it;
// }
// std::cout << "\n";
//}
//std::cout <<"building tree..."<<std::flush;
////////////////////////////////////////////////////////////////
//build refined alignment graph
_makeAlignmentGraphFromRefinedSegments(all_nodes,alis,score_type,seq,seq_map,ali_graph,tag,annotation);
}
///////WRAPPERS
//exact refinement, score type given
template<typename TAlignmentString, typename TScoreValue,typename TScoreSpec,typename TOutGraph, typename TSequence, typename TSetSpec>
void
matchRefinement(TAlignmentString & alis,
StringSet<TSequence, TSetSpec> & seq,
Score<TScoreValue,TScoreSpec> & score_type,
TOutGraph & ali_graph)
{
//min_fragment_len = 1 ==> Exact cutting
bool anno = false;
matchRefinement(alis,seq,score_type,ali_graph,1,anno,ExactRefinement());
}
//exact refinement, score type not given
template<typename TFragmentString, typename TOutGraph, typename TSequence, typename TSetSpec>
void
matchRefinement(TFragmentString & matches,
StringSet<TSequence, TSetSpec> & strSet,
TOutGraph & ali_graph)
{
typename Cargo<TOutGraph>::Type fake_score = 1;
bool anno = false;
matchRefinement(matches,strSet,fake_score,ali_graph,1,anno,ExactRefinement());
}
} // namespace seqan2
#endif // #ifndef SEQAN_INCLUDE_SEQAN_GRAPH_ALGORITHM_REFINE_EXACT_H_
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