main.cpp

/*The MIT License (MIT)

Copyright (c) 2017 Fan Zhang, Hyun Min Kang

Permission is hereby granted, free of charge, to any person obtaining a copy
of this software and associated documentation files (the "Software"), to deal
in the Software without restriction, including without limitation the rights
to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
copies of the Software, and to permit persons to whom the Software is
furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in all
copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
SOFTWARE.
 */
#include <fstream>
#include <iostream>
#include <sstream>
#include <stdexcept>

#include "ContaminationEstimator.h"
#include "PhoneHome.h"
#include "SVDcalculator.h"
#include "htslib/sam.h"
#include "params.h"
#include "backward.hpp"

#define VERSION "2.0.1"

int execute(int argc, char **argv) {

  std::string UDPath("Empty"), PCPath("Empty"), MeanPath("Empty"),
      BedPath("Empty"), BamFileList("Empty"), BamFile("Empty"),
      RefPath("Empty"), outputPrefix("result"), PileupFile("Empty"),
      SVDPrefix("Empty");
  std::string knownAF("Empty");
  std::string RefVCF("Empty");
  std::string fixPC("Empty");
  double fixAlpha(-1.), epsilon(1e-8);
  bool withinAncestry(false), outputPileup(false), verbose(false),
      disableSanityCheck(false);
  int nfiles(0), seed(12345), nPC(2), nthread(4);
  /// mpileup arguments
  mplp_conf_t mplp;
  memset(&mplp, 0, sizeof(mplp_conf_t));
  mplp.min_mq = 2;
  mplp.min_baseQ = 13;
  mplp.capQ_thres = 40;
  mplp.max_depth = MPLP_MAX_DEPTH;
  mplp.max_indel_depth = MPLP_MAX_INDEL_DEPTH;
  mplp.openQ = 40;
  mplp.extQ = 20;
  mplp.tandemQ = 100;
  mplp.min_frac = 0.002;
  mplp.min_support = 1;
  bool noOrphan = false;
  mplp.flag = /*MPLP_NO_ORPHAN |*/ MPLP_REALN | MPLP_SMART_OVERLAPS;
  mplp.rflag_filter = BAM_FUNMAP | BAM_FSECONDARY | BAM_FQCFAIL | BAM_FDUP;
  mplp.output_fname = NULL;
  ///
  paramList pl;
  BEGIN_LONG_PARAMS(longParameters)
  LONG_PARAM_GROUP(
      "Input/Output Files",
      "Input/Output files for the program[Complete Path Recommended]")
  LONG_STRING_PARAM("BamFile", &BamFile,
                    "[String] Bam or Cram file for the sample[Required if "
                    "--PileupFile not specified]")
  LONG_STRING_PARAM("PileupFile", &PileupFile,
                    "[String] Pileup file for the sample[Required if --BamFile "
                    "not specified]")
  LONG_STRING_PARAM("Reference", &RefPath, "[String] Reference file[Required]")
  LONG_STRING_PARAM("SVDPrefix", &SVDPrefix,
                    "[String] SVD related files prefix(normally shared by .UD, "
                    ".mu and .bed files)[Required]")
  LONG_STRING_PARAM("Output", &outputPrefix,
                    "[String] Prefix of output files[optional]")
  LONG_PARAM_GROUP("Model Selection Options",
                   "Options to adjust model selection and parameters")
  LONG_PARAM("WithinAncestry", &withinAncestry,
             "[Bool] Enabling withinAncestry assume target sample and "
             "contamination source are from the same "
             "populations,[default:BetweenAncestry] otherwise")
  LONG_PARAM("DisableSanityCheck", &disableSanityCheck,
             "[Bool] Disable marker quality sanity check(no marker "
             "filtering)[default:false]")
  LONG_INT_PARAM("NumPC", &nPC,
                 "[Int] Set number of PCs to infer Allele Frequency[optional]")
  LONG_STRING_PARAM(
      "FixPC", &fixPC,
      "[String] Input fixed PCs to estimate Alpha[format PC1:PC2:PC3...]")
  LONG_DOUBLE_PARAM("FixAlpha", &fixAlpha,
                    "[Double] Input fixed Alpha to estimate PC coordinates")
  LONG_STRING_PARAM("KnownAF", &knownAF,
                    "[String] known allele frequency file "
                    "(chr\tpos\tfreq)[Optional]")
  LONG_INT_PARAM("NumThread", &nthread,
                 "[Int] Set number of threads in likelihood "
                 "calculation[default:4]")
  LONG_INT_PARAM("Seed", &seed, "[Int] Random number seed[default:12345]")
  LONG_DOUBLE_PARAM("Epsilon", &epsilon,
                    "[Double] Minimization procedure convergence "
                    "threshold, usually a trade-off bettween accuracy and "
                    "running time[default:1e-10]")
  LONG_PARAM("OutputPileup", &outputPileup, "[Bool] If output temp pileup file")
  LONG_PARAM("Verbose", &verbose,
             "[Bool] If print the progress of the method on "
             "the screen")
  LONG_PARAM_GROUP("Construction of SVD Auxiliary Files",
                   "Use these options when generating SVDPrefix files")
  LONG_STRING_PARAM("RefVCF", &RefVCF,
                    "[String] VCF file from which to extract reference "
                    "panel's genotype matrix[Required if no SVD files "
                    "available]")
  LONG_PARAM_GROUP("Pileup Options", "Arguments for pileup info extraction")
  LONG_INT_PARAM("min-BQ", &mplp.min_baseQ,
                 "[Int] skip bases with baseQ/BAQ smaller than min-BQ")
  LONG_INT_PARAM("min-MQ", &mplp.min_mq,
                 "[Int] skip alignments with mapQ smaller than min-MQ")
  LONG_INT_PARAM("adjust-MQ", &mplp.capQ_thres,
                 "[Int] adjust mapping quality; "
                 "recommended:50, disable:0")
  LONG_INT_PARAM("max-depth", &mplp.max_depth, "[Int] max per-file depth")
  LONG_PARAM("no-orphans", &noOrphan, "[Bool] do not use anomalous read pairs")
  LONG_INT_PARAM("incl-flags", &mplp.flag,
                 "[Int] required flags: skip reads with mask bits unset")
  LONG_INT_PARAM("excl-flags", &mplp.rflag_filter,
                 "[Int] filter flags: skip reads with mask bits set")

  LONG_PARAM_GROUP("Deprecated Options",
                   "These options still are available but not recommended")
  LONG_STRING_PARAM("UDPath", &UDPath,
                    "[String] UD matrix file from SVD result "
                    "of genotype matrix")
  LONG_STRING_PARAM("MeanPath", &MeanPath,
                    "[String] Mean matrix file of genotype matrix")
  LONG_STRING_PARAM("BedPath", &BedPath,
                    "[String] Bed file for markers used in this analysis,1 "
                    "based "
                    "pos(chr\tpos-1\tpos\trefAllele\taltAllele)[Required]")
  END_LONG_PARAMS();

  pl.Add(new longParams("Available Options", longParameters));
  pl.Read(argc, argv);
  pl.Status();

  /// Pass along mpileup arguments
  if (noOrphan)
    mplp.flag |= MPLP_NO_ORPHAN;
  else
    mplp.flag &= 0XFFFFFFFF ^ MPLP_NO_ORPHAN;
  /// End of mpileup parsing

  if (RefVCF == "Empty") {
    if (SVDPrefix == "Empty") {
      if (UDPath == "Empty") {
        error("--UDPath is required when --RefVCF is absent");
        exit(EXIT_FAILURE);
      }
      if (MeanPath == "Empty") {
        error("--MeanPath is required when --RefVCF is absent");
        exit(EXIT_FAILURE);
      }
      if (BedPath == "Empty") {
        error("--BedPath is required when --RefVCF is absent");
        exit(EXIT_FAILURE);
      }
    } else {
      UDPath = SVDPrefix + ".UD";
      MeanPath = SVDPrefix + ".mu";
      BedPath = SVDPrefix + ".bed";
    }
  } else // SVD on the fly
  {
    notice(
        "Specified --RefVCF reference panel VCF file, doing SVD on the fly...");
    notice("This procedure will generate SVD matrices as [RefVCF path].UD and "
           "[RefVCF path].mu");
    notice("You may specify --SVDPrefix [RefVCF path](or --UDPath [RefVCF "
           "path].UD and --MeanPath [RefVCF path].mu) in future use");
    SVDcalculator calculator;
    calculator.ProcessRefVCF(RefVCF);
    UDPath = RefVCF + ".UD";
    MeanPath = RefVCF + ".mu";
    BedPath = RefVCF + ".bed";
    notice("Success!");
    return 0;
  }

  ////patch to PC path
    PCPath=UDPath.substr(0,UDPath.size()-3)+".V";
    ////

    if (RefPath == "Empty") {
        error("--Reference is required");
        exit(EXIT_FAILURE);
    }
    if (BamFile != "Empty") {
        nfiles = 1;
    }
//    else if (BamFileList !="Empty")
//    {
//        nfiles=2;
//    }
    else if(PileupFile != "Empty")
    {

    }
    else {
        error("--BamFile or --PileupFile is required");
        exit(EXIT_FAILURE);
    }

    ContaminationEstimator Estimator(nPC, BedPath.c_str(), nthread, epsilon);

    Estimator.verbose=verbose;
    Estimator.seed = seed;
    Estimator.isHeter = !withinAncestry;
    Estimator.isSanityCheckDisabled = disableSanityCheck;

    //std::cerr<<"NumMarker:"<<Estimator.NumMarker<<" and UD size:"<<Estimator.UD.size()<<std::endl;
    if(fixPC!="Empty") {// parse --fixPC
        notice("you specified --fixPC, this will overide dynamic estimation of PCs");
        notice("parsing the PCs");
        std::stringstream ss(fixPC);
        std::string token;
        std::vector<PCtype> tmpPC;
        while(std::getline(ss, token, ':')) {
            tmpPC.push_back(atof(token.c_str()));
        }
        if(tmpPC.size() > nPC)
            warning("parameter --fixPC provided larger dimension than parameter --numPC(default value 2) and hence will be truncated");
        if(tmpPC.size() < nPC)
            error("parameter --fixPC provided smaller dimension than parameter --numPC(default value 2)");
        for (int i = 0; i < nPC; ++i) {
            Estimator.PC[1][i]=tmpPC[i];
        }
        Estimator.isPCFixed = true;
    }
    else if(fabs(fixAlpha + 1.)>std::numeric_limits<double>::epsilon()) {
        notice("you specified --fixAlpha, this will overide dynamic estimation of alpha");
        Estimator.alpha = fixAlpha;
        Estimator.isAlphaFixed = true;
    }
    if(knownAF!="Empty") {
        Estimator.isAFknown = true;
        Estimator.isPCFixed = true;
        Estimator.isHeter =false; //under --knownAF condition, we assume WithinAncestry model
        Estimator.ReadAF(knownAF);
    }

    Estimator.ReadSVDMatrix(UDPath, PCPath, MeanPath);

    if(nfiles)
      Estimator.ReadBam(BamFile.c_str(), RefPath.c_str(), BedPath.c_str(),
                        &mplp);
    else
        Estimator.ReadPileup(PileupFile);


    if(outputPileup)
    {
        std::string fileName(outputPrefix+".Pileup");
        std::ofstream fout(fileName);
        if(not fout.is_open())
        {
            error("Open file %s failed!",fileName.c_str());
            exit(EXIT_FAILURE);
        }
        for(auto item:Estimator.BedVec)
        {
            if(Estimator.viewer.posIndex.find(item.chr)==Estimator.viewer.posIndex.end())//chr existed
                continue;
            else if(Estimator.viewer.posIndex[item.chr].find(item.end)==Estimator.viewer.posIndex[item.chr].end())
                continue;

            if(Estimator.viewer.GetBaseInfoAt(item.chr,item.end).size() > 0) {
                fout << item.chr << "\t" << item.end << "\t" << Estimator.ChooseBed[item.chr][item.end].first << "\t"
                     << Estimator.viewer.GetBaseInfoAt(item.chr, item.end).size() << "\t";
                for (auto base:Estimator.viewer.GetBaseInfoAt(item.chr, item.end))
                    fout << base;
                fout << "\t";
                for (auto qual:Estimator.viewer.GetQualInfoAt(item.chr, item.end))
                    fout << qual;
                fout << std::endl;
            }
        }
        fout.close();
        if(!fout)
        {
            error("Errors detected when writing to file %s !",fileName.c_str());
            exit(EXIT_FAILURE);
        }
    }

    if(!disableSanityCheck) {
        if (Estimator.IsSanityCheckOK())
            notice("Passing Marker Sanity Check...");
        else {
            warning("Insufficient Available markers, check input bam depth distribution in output pileup file after specifying --OutputPileup");
            exit(EXIT_FAILURE);
        }
    }

    Estimator.OptimizeLLK(outputPrefix);

    {//output vb1 compatible result
        const char *headers = "#SEQ_ID\tRG\tCHIP_ID\t#SNPS\t#READS\tAVG_DP\tFREEMIX\tFREELK1\tFREELK0\tFREE_RH\tFREE_RA\tCHIPMIX\tCHIPLK1\tCHIPLK0\tCHIP_RH\tCHIP_RA\tDPREF\tRDPHET\tRDPALT";
        std::string fileName(outputPrefix + ".selfSM");
        std::ofstream fout(fileName);
        if(not fout.is_open())
        {
            error("Open file %s failed!",fileName.c_str());
            exit(EXIT_FAILURE);
        }
        fout << headers << std::endl;
        fout << Estimator.viewer.SEQ_SM << "\tNA\tNA\t" << Estimator.NumMarker << "\t";
        if(Estimator.isPileupInput)
            fout <<"NA";
        else fout<<Estimator.viewer.numBases;
        fout << "\t" << Estimator.viewer.avgDepth << "\t"
             << ((Estimator.fn.globalAlpha < 0.5) ? Estimator.fn.globalAlpha : (1.f - Estimator.fn.globalAlpha)) << "\t"
             << -Estimator.fn.llk1 << "\t" << -Estimator.fn.llk0 << "\t" << "NA\tNA\t"
             << "NA\tNA\tNA\tNA\tNA\t"
             << "NA\tNA\tNA" << std::endl;
        fout.close();
        if(!fout)
        {
            error("Errors detected when writing to file %s !",fileName.c_str());
            exit(EXIT_FAILURE);
        }
    }
    notice("Success!");
    return 0;
}

// main function of verifyBamID
int main(int argc, char** argv) {
    fprintf(stderr, "VerifyBamID2: A robust tool for DNA contamination estimation from sequence reads using ancestry-agnostic method.\n\n");
    fprintf(stderr, " Version:%s\n",VERSION);
    fprintf(stderr, " Copyright (c) 2009-2020 by Hyun Min Kang and Fan Zhang\n");
    fprintf(stderr, " This project is licensed under the terms of the MIT license.\n");

#if DEBUG == 1
    using namespace backward;
    std::vector<int> signals;
    signals.push_back(SIGSEGV);
    SignalHandling sh(signals);
    std::cout << std::boolalpha << "enable segfault handler... " << sh.loaded() << std::endl;
    std::cout << std::boolalpha << "sh.loaded() == " << sh.loaded() << std::endl;
#endif
    int returnVal = 0;
    String compStatus;
    PhoneHome::allThinning = 50;
    try
    {
        returnVal = execute(argc, argv);
    }
    catch(std::runtime_error& e)
    {
        returnVal = -1;
        compStatus = "Exception";
        PhoneHome::completionStatus(compStatus.c_str(),"VerifyBamID2");
        std::string errorMsg = "Exiting due to ERROR:\n\t";
        errorMsg += e.what();
        std::cerr << errorMsg << std::endl;
        return returnVal;
    }
    catch(std::exception& e)
    {
        returnVal = -1;
        std::string errorMsg = "Exiting due to ERROR:\n\t";
        errorMsg += e.what();
        std::cerr << errorMsg << std::endl;
        return returnVal;
    }
    compStatus = returnVal;
    PhoneHome::completionStatus(compStatus.c_str(),"VerifyBamID2");
    return(returnVal);
}