File: merci.cpp

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/*****************************************************************************
 *   GATB : Genome Assembly Tool Box
 *   Copyright (C) 2017  INRIA
 *   Authors: R.Chikhi, G.Rizk, E.Drezen
 *
 *  This program is free software: you can redistribute it and/or modify
 *  it under the terms of the GNU Affero General Public License as
 *  published by the Free Software Foundation, either version 3 of the
 *  License, or (at your option) any later version.
 *
 *  This program is distributed in the hope that it will be useful,
 *  but WITHOUT ANY WARRANTY; without even the implied warranty of
 *  MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
 *  GNU Affero General Public License for more details.
 *
 *  You should have received a copy of the GNU Affero General Public License
 *  along with this program.  If not, see <http://www.gnu.org/licenses/>.
*****************************************************************************/

/* merci does the mercy-kmer assembly trick of megahit
 *
 * IMPORTANT: really need to set k as the same as the one that was used for creating those contigs/unitigs,
 * otherwise it will still run but the glue will make the machine run out of memory :/
 */

/********************************************************************************/

#include <gatb/gatb_core.hpp>
#include <iostream>
#include <fstream>
#include <string>
#include <set>
#include <unordered_map>
#include <iomanip> // for setprecision

const int max_delta = 5; // important parameter

using namespace std;

static void file_copy(string from, string to) // http://stackoverflow.com/questions/10195343/copy-a-file-in-a-sane-safe-and-efficient-way
{
    std::ifstream  src(from, std::ios::binary);
    std::ofstream  dst(to,   std::ios::binary);
    dst << src.rdbuf();
}

static void file_append(string dest, string with_file)
{
    std::ofstream fout ( dest, std::ios_base::app);
    std::ifstream f2 ( with_file);
    fout << f2.rdbuf();
}

template <int span> using assembly_index_t = std::unordered_map<typename Kmer<span>::Type,uint64_t>;

typedef std::unordered_map<uint64_t,set<uint64_t>> connections_index_t ;
typedef std::unordered_map<uint64_t,set<string>> connections_t ;

template<int span>
void index_assembly(string assembly, int k, int nb_threads, bool verbose, assembly_index_t<span>& index)
{
    if (verbose)
        std::cout << "indexing assembly extremities" << std::endl;

    class IndexAssembly
    {
        typedef typename Kmer<span>::ModelCanonical ModelCanon;
        
        int k;
        ModelCanon modelCanon;
        uint64_t current_seq;
        assembly_index_t<span> &index;
        int _currentThreadIndex; // for later
        bool debug;

        public: 
        IndexAssembly(int k, assembly_index_t<span> &index) : 
                      k(k), modelCanon(k), current_seq(0),
                         index(index), _currentThreadIndex(-1), debug(false)
        {}
 
        void operator()     (const Sequence& sequence) {
            const string seq = sequence.toString(); 
            const string comment = sequence.getComment();

            const bool no_link_left = comment.find("L:-") == string::npos;
            const bool no_link_right = comment.find("L:+") == string::npos;

            if (no_link_left)
            {
                const string kmerBegin = seq.substr(0, k );
                const typename ModelCanon::Kmer kmmerBegin = modelCanon.codeSeed(kmerBegin.c_str(), Data::ASCII);
                bool rc = modelCanon.toString(kmmerBegin.value()) != kmerBegin; // could be optimized
                ExtremityInfo e (current_seq, rc, UNITIG_BEGIN); /* actually we dont know if its false/UNITIG_BEGIN or reverse/UNITIG_END but should think about it, for now, putting naive*/ 
                index[kmmerBegin.value()] = e.pack();
                if (debug) std::cout << "index left kmer " << modelCanon.toString(kmmerBegin.value()) << " of contig " << current_seq << std::endl; 
            }

            if (no_link_right)
            {
                const string kmerEnd = seq.substr(seq.size() - k , k );
                const typename ModelCanon::Kmer kmmerEnd = modelCanon.codeSeed(kmerEnd.c_str(), Data::ASCII);
                bool rc =  modelCanon.toString(kmmerEnd.value()) != kmerEnd; // could be optimized
                ExtremityInfo e (current_seq, rc, UNITIG_END); 
                index[kmmerEnd.value()] = e.pack();
                if (debug) std::cout << "index right kmer " << modelCanon.toString(kmmerEnd.value()) << " of contig " << current_seq << std::endl; 
            }
            current_seq++;
        }
    };

    IndexAssembly indexAssembly(k, index);

    IBank *in = Bank::open (assembly);
    auto it = in->iterator();    
    for (it->first (); !it->isDone(); it->next())
        indexAssembly(it->item());
}

/* populates connections_index and connections
 
 * may not insert if it detects that something is not right with respect to orientations:
     * ctg1 ----------[kmer1]
     * ctg2 ----------[kmer2]
     * is only possible when read is
     * [kmer1]---[kmer2 rc] or [kmer1 rc]---[kmer2],
     * where rc is relative to the orientation of the kmer in ctg1/ctg2
     *
     * similarly,
     * ctg1 ----------[kmer1]
     * ctg2 [kmer2]---------
     * is only possible when read is
     * [kmer1]----[kmer2] or [kmer2 rc]----[kmer1 rc]]
     *
     * now, consider that kmer1 is either in its forward or reverse orientation with respect to the contig.
*/
static void 
insert_connection(uint64_t previous_extremityinfo, uint64_t current_extremityinfo, connections_index_t &connections_index, connections_t &connections, int previous_pos, int current_pos, bool previous_rc, bool current_rc, const string &seq, int k, bool verbose)
{
    /* there are two ways to write a connection and we need to write them both */
    ExtremityInfo pe(previous_extremityinfo); 
    ExtremityInfo ce(current_extremityinfo); 

    if (pe.unitig == ce.unitig) return; // one case where we actually don't insert
   
    if (pe.rc) previous_rc = !previous_rc; // haha i'm not proud of myself but i didn't carefully check that code. but it seems to make sense and no crashes anymore, so..
    if (ce.rc) current_rc  = !current_rc; 
    if (pe.pos == ce.pos && (previous_rc == current_rc)) return;
    if (pe.pos != ce.pos && (previous_rc != current_rc)) return;

    // at this points we don't need to care about rc anymore, we know that it's all good. somehow_merge() will somehow figure it out

    uint64_t ce_packed = ce.pack_norc();
    uint64_t pe_packed = pe.pack_norc();
    connections_index[pe_packed].insert(ce_packed);
    connections_index[ce_packed].insert(pe_packed);

    // this the part of the read that is the connection sequence
    string connection = seq.substr(previous_pos,current_pos-previous_pos+k);
    connections[pe_packed].insert(connection);
    connections[ce_packed].insert(connection);

    //if (verbose)        std::cout << "found connection between contig " << pe.unitig << " and contig " << ce.unitig << " : " << seq.substr(previous_pos,current_pos-previous_pos+k) << std::endl; 
}


template<int span>
void search_reads(string reads, int k, int nb_threads, bool verbose, assembly_index_t<span>& assembly_index, connections_index_t &connections_index, connections_t &connections)
{
    if (verbose)
        std::cout << "searching reads for assembly extremities" << std::endl;

    std::mutex insertMutex;
    uint64_t nb_found_connections = 0;

    class SearchReads 
    {
        typedef typename Kmer<span>::ModelCanonical ModelCanon;
        
        int k;
        bool verbose;
        ModelCanon modelCanon;
        connections_index_t &connections_index;
        connections_t &connections;
        std::mutex &insertMutex;
        assembly_index_t<span> &assembly_index;
        int _currentThreadIndex; // for later
        uint64_t &nb_found_connections;

        public: 

        SearchReads(int k, bool verbose, assembly_index_t<span> &assembly_index, connections_index_t &connections_index, connections_t &connections, std::mutex &insertMutex, uint64_t &nb_found_connections) : 
                      k(k), verbose(verbose), modelCanon(k), connections_index(connections_index), connections(connections), insertMutex(insertMutex),
                         assembly_index(assembly_index), _currentThreadIndex(-1), nb_found_connections(nb_found_connections)
        {}
 
        void operator()     (/* not making it const because if itKmer */ Sequence& sequence) {
            const string seq = sequence.toString(); 
            const string comment = sequence.getComment();

            typename Kmer<span>::ModelCanonical::Iterator itKmer (modelCanon);
            itKmer.setData (sequence.getData());
            int previous_pos = -1;
            int current_pos = 0;
            uint64_t previous_extremityinfo = 0;
            bool previous_rc = false, current_rc = false;

            //std::cout << "seq: " << seq << std::endl;
            for (itKmer.first(); !itKmer.isDone(); itKmer.next())
            {
                typedef typename Kmer<span>::Type Type;

                Type kmer =  itKmer.item().value();
                //std::cout << "testing kmer " << modelCanon.toString(kmer) << std::endl;
                auto hit = assembly_index.find(kmer) ;
                if (hit != assembly_index.end())
                {
                    const string kmer_seq = seq.substr(current_pos,k);
                    if (kmer_seq.find("N") != string::npos)
                        continue;//discard kmers with N's
                    current_rc = modelCanon.toString(kmer) != kmer_seq;
                    uint64_t current_extremityinfo = hit->second;
                    if (previous_pos != -1 && current_pos - previous_pos < max_delta)
                    {
                        insertMutex.lock();
                        insert_connection(previous_extremityinfo, current_extremityinfo, connections_index, connections, previous_pos, current_pos, previous_rc, current_rc, seq, k, verbose);
                        nb_found_connections++;
                        insertMutex.unlock();
                    }
                    previous_pos    = current_pos;
                    previous_rc     = current_rc;
                    previous_extremityinfo = current_extremityinfo;
                }
                current_pos++;
            }
        }
    };

    SearchReads searchReads(k, verbose, assembly_index, connections_index, connections, insertMutex, nb_found_connections);

    IBank *in = Bank::open (reads);
    Dispatcher dispatcher (nb_threads);
    dispatcher.iterate (in->iterator(), searchReads);
    /*auto it = in->iterator();     // single threaded version
    for (it->first (); !it->isDone(); it->next())
        searchReads(it->item());
    */
    if (verbose) std::cout << "found " << nb_found_connections << " connections" << std::endl;
}

// there are not so many places where i need a sequence revcomp. GraphUnitigs and here.
static
char revcomp (char s) {
    if (s == 'A') return 'T';
    else if (s == 'C') return 'G';
    else if (s == 'G') return 'C';
    else if (s == 'T') return 'A';
    else if (s == 'a') return 't';
    else if (s == 'c') return 'g';
    else if (s == 'g') return 'c';
    else if (s == 't') return 'a';
    return 'N';
}

static string revcomp (const string &s) {
    string rc;
    for (signed int i = s.length() - 1; i >= 0; i--) {rc += revcomp(s[i]);}
    return rc;
}

/* naive, cause I'm lazy */
static bool 
somehow_merge(string &seq, const string &extension, unsigned int k, bool verbose, int pos)
{
    const string rev_extension = revcomp(extension);
    
    const string extrem = seq.substr(pos,k);
    const vector<string> extensions {extension, rev_extension};
    for (auto e: extensions)
    {
        if (pos == 0)
        {
            /*     [     ]---seq----
             *  -e-[     ]
             */
            if (e.substr(e.size()-k) == extrem)
            {
                seq = e.substr(0,e.size()-k) + seq;
                return true;
            }
        }
        else
        {
            /*    ----seq-----[      ]
             *                [      ]--e--
             */
            if (e.substr(0,k) == extrem)
            {
                seq = seq + e.substr(k);
                return true;
            }
        }
    }
    //std::cout << "oops, couldn't somehow merge " << seq << " with " << extension << std::endl;
    /* yeah well, that's the following situation (all in forward orientation, no rc):
     *  assembly: 
     *    [kmer1]--------
     *    [kmer2]--------
     *  read:
     *    --[kmer1]--[kmer2]--
     *  may occurs due to EC removal
     *
     * 
     * --------------[kmer2]----- 
     *              /
     *             / EC
     *            /
     * -----[kmer1]----
     *
     *  so whenever this situation occurs, let's not glue again anyhow
     */
    return false;
}

/* examines connections_index to see how contigs are connected to each other
 * returns true for "compactable" nodes, those which have single out-neighbor and single-inneighbor in the connection graph
 * oh indeed, this is a compaction problem all over again
 * well no wonder why i'm using bglue after then
 *
 * unpure function: updates seqs_to_glue
 */
static bool maybe_merge(uint64_t packed, connections_index_t &connections_index, connections_t &connections, set<uint64_t> &seqs_to_glue, bool given_verbose, string &seq, int k, int pos)
{
    bool verbose = given_verbose;

    if (connections_index.find(packed) == connections_index.end())
        return false;

    ExtremityInfo current(packed);

    set<uint64_t> &links = connections_index[packed];
    if (links.size() != 1)
    {
        if (verbose) std::cout << "bad conn (" << (pos==UNITIG_BEGIN?"beg":"end") << "), contig: " << current.unitig << (current.pos==UNITIG_BEGIN?"beg":"end") << " connections: " << links.size() << std::endl;
        return false;
    }

    ExtremityInfo other(*connections_index[packed].begin());

    // check the incoming links of that other
    if (connections_index[other.pack_norc()].size() != 1)
    {
        if (verbose) std::cout << "bad conn (" << (pos==UNITIG_BEGIN?"beg":"end") << "), other contig: " << other.unitig << (other.pos==UNITIG_BEGIN?"beg":"end") << " connections: " << connections_index[other.pack_norc()].size() << std::endl;
        return false;
    }

    if (connections[packed].size() != 1) // may return false if it was previously cleared
        return false;
    
    // all good, we keep this one
    // let's try to merge it
    
    const string extension = *(connections[packed].begin());
    if (!somehow_merge(seq, extension, k, verbose, pos==UNITIG_BEGIN?0:(seq.size()-k)))
        return false;

    // merge went okay!
    // to avoid redundancy, we delete the other
    if (verbose) std::cout << "good conn (" << (pos==UNITIG_BEGIN?"beg":"end") << "): " << current.unitig << " connections: " << links.size() << std::endl;
    if (verbose) std::cout << "clearing connections of contig " << other.unitig << std::endl;
    connections[other.pack_norc()].clear();
    seqs_to_glue.insert(other.pack_norc());
    return true; 
}

        
static void
parse_unitig_header(string header, float& mean_abundance)
{
    bool debug = false;
    if (debug) std::cout << "parsing unitig links for " << header << std::endl;
    std::stringstream stream(header);
    while(1) {
        string tok;
        stream >> tok;
        if(!stream)
            break;

        if (tok.size() < 3)
            // that's the id, skip it
            continue;

        string field = tok.substr(0,2);

		if (field == "km")
		{
			mean_abundance = atof(tok.substr(tok.find_last_of(':')+1).c_str());
			//std::cout << "unitig " << header << " mean abundance " << mean_abundance << std::endl;
		}
	}
}


void renumber_glue_file(string glue_filename, uint64_t nb_out_tigs)
{
    {
        std::ifstream infile(glue_filename);
        std::ofstream outfile(glue_filename+".tmp");
        std::string line;
        uint64_t counter = 1;
        while (std::getline(infile, line))
        {
            if (line[0] == '>')
            {
                size_t space_pos = line.find(' ');
                /* // yolo
                if (space_pos >= line.size())
                {
                    std::cout << "error: no space in this glue file header (" << line << ") contact a developer." << std::endl;
                    exit(1);
                }
                */
                auto end_header = line.substr(space_pos);
                string new_header = ">" + std::to_string(nb_out_tigs+counter) + end_header;
                outfile << new_header << std::endl;
                counter++;
            }
            else
                outfile << line << std::endl;
        }
    } // closes files
    file_copy(glue_filename+".tmp",glue_filename);
    System::file().remove (glue_filename+".tmp");
}

static void 
extend_assembly_with_connections(const string assembly, int k, int nb_threads, bool verbose, connections_index_t &connections_index, connections_t &connections, BankFasta &out, BankFasta &glue)
{
    if (verbose)
        std::cout << "extending assembly with unambiguous connections" << std::endl;

    IBank *in = Bank::open (assembly);
    auto it = in->iterator();    
    uint64_t tig_index = 0;
    set<uint64_t> seqs_to_glue;

    for (it->first (); !it->isDone(); it->next())
    {
        const Sequence &sequence = it->item();
        string seq = sequence.toString(); 
        const string comment = sequence.getComment();

        bool debug = false;
        
        ExtremityInfo beg(tig_index, false, UNITIG_BEGIN);
        ExtremityInfo end(tig_index, false, UNITIG_END);
        bool lmark, rmark;

        // see if the contig was already previously marked as one to glue
        lmark = (seqs_to_glue.find(beg.pack_norc()) != seqs_to_glue.end());
        rmark = (seqs_to_glue.find(end.pack_norc()) != seqs_to_glue.end());

        if (debug) if (lmark || rmark) std::cout << "tig " << tig_index << " already marked with " << lmark << rmark << std::endl;
        
        if ((!lmark) && maybe_merge(beg.pack_norc(), connections_index, connections, seqs_to_glue, debug, seq, k, UNITIG_BEGIN)) // order of evaluation matters, as check_connection is unpure
            lmark = true;

        if ((!rmark) && maybe_merge(end.pack_norc(), connections_index, connections, seqs_to_glue, debug, seq, k, UNITIG_END))
            rmark = true;
        
        if (debug) std::cout << "tig " << tig_index << " new mark " << lmark << rmark << std::endl;

        Sequence s (Data::ASCII);
        s.getData().setRef ((char*)seq.c_str(), seq.size());
        s._comment = string(lmark?"1":"0")+string(rmark?"1":"0"); //We set the sequence comment.
        s._comment += " ";

        // add coverage information 
		float mean_abundance;
		parse_unitig_header(comment,mean_abundance);
		uint nb_kmers = seq.size() - k + 1;
		for (uint i = 0; i < nb_kmers; i++)
			s._comment += std::to_string((uint)mean_abundance) + " ";
        
        if (lmark || rmark)
            glue.insert(s); 
        else 
        {
            s._comment = comment;
            out.insert(s);
        }

        tig_index++;
    }
}

template<int span>
void merci(int k, string reads, string assembly, int nb_threads, bool verbose)
{
    if (verbose)
        cout << "k: " << k << " threads: " << nb_threads << " reads: " << reads << " assembly: " << assembly << endl;

    // make a copy of the assembly, and find links
    string linked_assembly = assembly + ".linked";
    file_copy(assembly, linked_assembly);
    uint64_t nb_tigs = 0;
    bool renumber_unitigs = true; // let's allow the input to be anything. Here it doesn't amtter much. We anyway renumber at the end
    link_tigs<span>( linked_assembly, k, nb_threads, nb_tigs, verbose, renumber_unitigs);

    // real trick here
    // tigs of length exactly k are annoying, they need to be handled carefully with UNITIG_BOTH positions
    // so to avoid that for now, I'm just going to do the rest of the program using (k-1)-mers, so that each tig has a clear beginning and end
    // we lose one nucleotide of specificity, should i'm willing to accept that for now
    k -= 1;

    // index extremities of assembly that do not have links
    assembly_index_t<span> index;
    index_assembly<span>(linked_assembly, k, nb_threads, verbose, index);

    // now pass the reads and find putative connections
    connections_index_t connections_index; // associates a contig to a connection
    connections_t connections; // a connection is basically a chunk of read linking two indexed kmers close to each other
    search_reads<span>(reads,k,nb_threads,verbose, index, connections_index, connections);

    // pass the assembly again and slightly extend some contigs with unambiguous connections
    System::file().remove (assembly+".merci");
    BankFasta out (assembly+".merci");
    BankFasta glue(assembly+".glue.glue"); // bglue will glue the .glue.glue to .glue
    extend_assembly_with_connections(assembly, k, nb_threads, verbose, connections_index, connections, out, glue);
    glue.flush();
   
    // glue what needs to be glued. magic, we're re-using bcalm code
    bglue<span> (nullptr /*no storage*/, assembly+".glue", k, 0, nb_threads, false, verbose);
  
    // renumber the .glue file just to avoid ID collision with .merci file
    renumber_glue_file(assembly+".glue", nb_tigs );
    
    // append glued to merci
    out.flush();
    file_append(assembly+".merci", assembly+".glue");

    // bglue drop links so let's recreate them 
    k += 1;
    file_copy(assembly+".merci", assembly+".merci.b4link");
    renumber_unitigs = true; // here it's absolutely mandatory to renumber if we want the output to be processed by minia
    link_tigs<span>( assembly+".merci", k, nb_threads, nb_tigs, verbose, false, renumber_unitigs);
}

class Merci : public gatb::core::tools::misc::impl::Tool
{
public:

    /** Constructor. */
    Merci () : Tool("merci")
    {

#ifdef GIT_SHA1
        std::cout << "Merci for Minia 3, git commit " << GIT_SHA1 << std::endl;
#endif

        // reinit the parser to get rid of options added by the Tool class
        setParser (new OptionsParser ("merci")); 
        OptionsParser* assemblyParser = new OptionsParser ("assembly");
        assemblyParser->push_front (new OptionOneParam ("-reads",       "input reads (fasta/fastq/compressed)",   true));
        assemblyParser->push_front (new OptionOneParam ("-assembly",    "assembly to improve",   true));
        assemblyParser->push_front (new OptionOneParam (STR_KMER_SIZE,    "kmer size",   true));
        assemblyParser->push_front (new OptionOneParam (STR_NB_CORES,    "number of threads",   false, "0")); // apparently its needed when there is no parser
        assemblyParser->push_front (new OptionOneParam (STR_VERBOSE,  "verbosity level", false, "1"));
        getParser()->push_back (assemblyParser);
    }

    struct Parameter
    {
        string reads, assembly;
        int k,t;
        bool verbose;
    };
    
    template<size_t span>
    struct MerciFunctor
    {
        void operator() (Parameter parameter)
        {
            merci<span>(parameter.k,parameter.reads,parameter.assembly,parameter.t,parameter.verbose);
        }
    };

    /** \copydoc Tool::execute. */
    void  execute ()
    {
        /** we get the kmer size chosen by the end user. */
        int kmerSize = getInput()->getInt (STR_KMER_SIZE);
        string reads = getInput()->getStr ("-reads");
        string assembly = getInput()->getStr ("-assembly");
        int nb_threads = getInput()->getInt(STR_NB_CORES);
        bool verbose =  getInput()->getInt("-verbose") == 1; 
        /** We launch Merci with the correct Integer implementation according to the choosen kmer size. */
        Integer::apply<MerciFunctor,Parameter> (kmerSize, Parameter{reads,assembly,kmerSize, nb_threads, verbose});
        
        getInfo()->add (1, getTimeInfo().getProperties("time"));
    }


private:


};


/********************************************************************************/

int main (int argc, char* argv[])
{
    // We define a try/catch block in case some method fails (bad filename for instance)
    try
    {
        /** We execute dsk. */
        Merci().run (argc, argv);
    }

    catch (OptionFailure& e)
    {
        return e.displayErrors (cout);
    }

    catch (Exception& e)
    {
        cerr << "EXCEPTION: " << e.getMessage() << endl;
        return EXIT_FAILURE;
    }

    return EXIT_SUCCESS;
}