rna_features.cc

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// -*- mode:c++;tab-width:2;indent-tabs-mode:t;show-trailing-whitespace:t;rm-trailing-spaces:t -*-
// vi: set ts=2 noet:
//
// (c) Copyright Rosetta Commons Member Institutions.
// (c) This file is part of the Rosetta software suite and is made available under license.
// (c) The Rosetta software is developed by the contributing members of the Rosetta Commons.
// (c) For more information, see http://www.rosettacommons.org. Questions about this can be
// (c) addressed to University of Washington UW TechTransfer, email: license@u.washington.edu.

/// @file
/// @brief
/// @author Rhiju, rhiju@stanford.edu

////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////
//  RNA features -- produce a huge dump of features that can be regressed against 'deep chemical profiling' data
//  that is being collected in the Das lab.  -- initially craeted on May 7, 2013 by Rhiju.
//
//  Uses new RDAT 'feature' output format.
//
////////////////////////////////////////////////////////////////////////////////////////////////////////////////////////

// libRosetta headers
#include <core/types.hh>
#include <core/chemical/AA.hh>
#include <core/chemical/ChemicalManager.hh>
#include <core/chemical/VariantType.hh>
#include <core/conformation/Residue.hh>
#include <core/conformation/ResidueFactory.hh>
#include <core/scoring/func/HarmonicFunc.hh>
#include <core/chemical/rna/util.hh>
#include <core/scoring/ScoreFunction.hh>
#include <core/scoring/methods/EnergyMethodOptions.hh>
#include <core/scoring/sasa.hh>
#include <core/scoring/ScoringManager.hh>
#include <core/scoring/rna/RNA_LowResolutionPotential.hh>
#include <core/pose/rna/RNA_BaseDoubletClasses.hh>
#include <core/scoring/rna/RNA_CentroidInfo.hh>
#include <core/scoring/rna/RNA_ScoringInfo.hh>
#include <core/scoring/rna/data/RNA_DMS_Potential.hh>
#include <core/scoring/rna/data/RNA_DMS_LowResolutionPotential.hh>
#include <core/io/rna/RDAT.hh>
#include <core/scoring/hbonds/HBondSet.hh>
#include <core/scoring/hbonds/HBondOptions.hh>
#include <core/scoring/hbonds/hbonds.hh>

#include <core/id/AtomID_Map.hh>
#include <core/id/AtomID.hh>
#include <core/id/NamedAtomID.hh>
#include <core/id/DOF_ID.hh>
#include <core/init/init.hh>
#include <core/io/pdb/pdb_writer.hh>
#include <core/kinematics/AtomTree.hh>
#include <core/kinematics/FoldTree.hh>
#include <core/kinematics/Jump.hh>
#include <core/kinematics/Stub.hh>

#include <core/pose/Pose.hh>
#include <core/pose/PDBInfo.hh>
#include <core/pose/PDBInfo.fwd.hh>
#include <core/pose/util.hh>
#include <core/pose/rna/RNA_BasePairClassifier.hh>
#include <core/import_pose/import_pose.hh>

#include <devel/init.hh>

#include <protocols/farna/util.hh>
#include <protocols/viewer/viewers.hh>

#include <basic/options/option.hh>
#include <basic/options/option_macros.hh>
#include <basic/database/open.hh>

#include <utility/vector1.hh>
#include <utility/tools/make_vector1.hh>
#include <utility/io/ozstream.hh>
#include <utility/io/izstream.hh>
#include <utility/file/FileName.hh>

#include <numeric/xyzVector.hh>
#include <numeric/xyzMatrix.hh>
#include <numeric/conversions.hh>
#include <numeric/constants.hh>

#include <ObjexxFCL/format.hh>
#include <ObjexxFCL/FArray1D.hh>
#include <ObjexxFCL/FArray2D.hh>
#include <ObjexxFCL/string.functions.hh>


// C++ headers
#include <fstream>
#include <iostream>
#include <string>

//silly using/typedef
// option key includes

#include <basic/options/keys/out.OptionKeys.gen.hh>
#include <basic/options/keys/in.OptionKeys.gen.hh>
#include <basic/options/keys/chemical.OptionKeys.gen.hh>

//Auto Headers
#include <core/conformation/Conformation.hh>
#include <core/scoring/constraints/Constraint.hh>
#include <numeric/xyz.functions.hh>

//Auto using namespaces
namespace ObjexxFCL { namespace format { } } using namespace ObjexxFCL::format; // AUTO USING NS
//Auto using namespaces end

using namespace core;
using namespace core::conformation;
//using namespace protocols;
using namespace basic::options::OptionKeys;
using namespace core::chemical::rna;

using utility::vector1;
using utility::tools::make_vector1;
using ObjexxFCL::format::I;
using ObjexxFCL::format::F;


typedef  numeric::xyzMatrix< core::Real > Matrix;


///////////////////////////////////////////////////////////////////////////
void
save_feature(  vector1< std::string > & feature_names,
  vector1< core::Real > & feature_vals,
  Size & feature_counter,
  std::string const & feature_name,
  core::Real const feature_val ){

  feature_counter++;

  if ( feature_counter > feature_names.size() ) feature_names.push_back( feature_name );
  runtime_assert( feature_counter <= feature_names.size() );

  feature_vals.push_back( feature_val );
}

///////////////////////////////////////////////////////////////////////////////
Size
rna_features_from_pose( core::io::rna::RDAT & rdat, pose::Pose & pose )
{
  using namespace core::conformation;
  using namespace core::chemical;
  using namespace core::scoring;
  using namespace core::scoring::rna::data;
  using namespace core::kinematics;
  using namespace core::id;
  using namespace protocols::farna;
  using namespace core::chemical::rna;

  vector1< std::string > feature_names;
  vector1< char > chains;
  vector1< char > seqchars;
  vector1< int > resnums;
  vector1< vector1< core::Real > > all_feature_vals;

  Size res_count( 0 ), num_features( 0 );
  Size const nres = pose.total_residue();
  core::pose::PDBInfoCOP pdb_info = pose.pdb_info();

  // sasa calculation
  AtomID_Map< core::Real > atom_sasa;
  utility::vector1< core::Real > rsd_sasa;
  core::Real const probe_radius( 1.4 );
  scoring::calc_per_atom_sasa( pose, atom_sasa, rsd_sasa, probe_radius, true );

  RNA_DMS_Potential & rna_dms_potential  = ScoringManager::get_instance()->get_RNA_DMS_Potential();
  pose.update_residue_neighbors();
  rna_dms_potential.initialize( pose );

  RNA_DMS_LowResolutionPotential & rna_dms_low_resolution_potential = ScoringManager::get_instance()->get_RNA_DMS_LowResolutionPotential();
  // rna_dms_low_resolution_potential.set_careful_base_pair_classifier( false );
  rna_dms_low_resolution_potential.initialize( pose );

  vector1< char  > nt_names = utility::tools::make_vector1( 'a', 'c', 'g', 'u' );
  Size const num_nt = nt_names.size();
  runtime_assert( num_nt == 4 );

  for ( Size i = 1; i <= nres; i++ ) {

    Residue const & rsd = pose.residue( i );
    if ( !rsd.is_RNA() ) continue;
    res_count++;

    seqchars.push_back( rsd.name1() );
    resnums.push_back( pdb_info->number( i ) );
    chains.push_back( pdb_info->chain( i ) );

    vector1< core::Real > feature_vals;
    Size feature_counter( 0 );

    // is_a, is_c, etc.
    vector1< bool > is_nt;
    vector1< std::string > is_nt_tag;
    for ( Size m = 1; m <= num_nt; m++ ) {
      is_nt.push_back( rsd.name1() == nt_names[m] );
      is_nt_tag.push_back( "is_" + std::string(&nt_names[m],1) /* man, converting char to string is a pain!*/ );
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m], is_nt[m] );
    }

    // look for O2' in WC sector -- probably explains rest of DMS protections. Note that this is general, so
    // perhaps should not be in a dms_low_resolution_potential, but instead in an rna_base_pair_info object?
    bool wc_near_o2prime = rna_dms_low_resolution_potential.get_wc_near_o2prime( pose, i );

    // probably makes sense to explicitly take product with is_a, etc. above -- in case classifier is not
    // smart about leveraging products of features.
    for ( Size m = 1; m <= num_nt; m++ ) {
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_wc_edge_paired"   ,
        rna_dms_low_resolution_potential.wc_edge_paired()[i]    * is_nt[m] );
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_hoog_edge_paired" ,
        rna_dms_low_resolution_potential.hoog_edge_paired()[i]  * is_nt[m]);
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_sugar_edge_paired",
        rna_dms_low_resolution_potential.sugar_edge_paired()[i] * is_nt[m]);
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_is_bulged",
        rna_dms_low_resolution_potential.is_bulged()[i] * is_nt[m] );
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_wc_near_o2prime"   , wc_near_o2prime * is_nt[m] );
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_wc_edge_paired_or_near_o2prime",
        ( wc_near_o2prime || rna_dms_low_resolution_potential.wc_edge_paired()[i] ) * is_nt[m] );
    }


    // What is hydrogen bonded?
    bool ade_n1_hbonded = is_nt[1] && rna_dms_potential.check_hbonded( pose, i, " N1 ", true /*acceptor*/ );

    for ( Size m = 1; m <= num_nt; m++ ) {

      // need an instance of this nucleotide to play around with.
      // This better have RNA residue types in it.
      ResidueTypeSet const & rsd_set = *rsd.residue_type_set();
      ResidueType const & rsd_type = *( rsd_set.get_representative_type_aa(  core::chemical::aa_from_oneletter_code( nt_names[m] ) ) );

      // what is hydrogen bonded? Acceptors.
      AtomIndices accpt_pos = rsd_type.accpt_pos();
      for ( Size k = 1; k <= accpt_pos.size(); k++ ) {
        std::string atom_name = rsd_type.atom_name( accpt_pos[ k ] );
        bool hbonded = is_nt[m] && rna_dms_potential.check_hbonded( pose, i, atom_name, true /*acceptor*/ );
        ObjexxFCL::strip_whitespace(atom_name);
        save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_"+atom_name+"_hbonded", hbonded);

        // special for DMS
        if ( m==1 ) save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_"+atom_name+"_hbonded"+"_and_N1_hbonded", hbonded && ade_n1_hbonded);
      }

      if ( m == 1 ) {
        bool ade_n1_chbonded( false );
        if ( is_nt[1] ) ade_n1_chbonded = rna_dms_potential.check_chbonded( pose, i, " N1 " );
        save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_N1_chbonded", ade_n1_chbonded );
        save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_N1_hbonded_or_chbonded",
          ade_n1_chbonded || ade_n1_hbonded );
      }


      // what is hydrogen bonded? Donor hydrogens.
      AtomIndices Hpos_polar = rsd_type.Hpos_polar();
      for ( Size k = 1; k <= Hpos_polar.size(); k++ ) {
        std::string atom_name = rsd_type.atom_name( Hpos_polar[ k ] );
        bool hbonded = is_nt[m] && rna_dms_potential.check_hbonded( pose, i, atom_name, false /*acceptor --> check for polar hydrogen names*/ );
        ObjexxFCL::strip_whitespace(atom_name);
        save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_"+atom_name+"_hbonded", hbonded);

        // special for DMS
        if ( m==1 ) save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_"+atom_name+"_hbonded"+"_and_N1_hbonded", hbonded && ade_n1_hbonded);
      }
    }


    //sasa
    for ( Size m = 1; m <= num_nt; m++ ) {

      // need an instance of this nucleotide to play around with.
      // This better have RNA residue types in it.
      ResidueTypeSet const & rsd_set = *rsd.residue_type_set();
      ResidueType const & rsd_type = *( rsd_set.get_representative_type_aa( core::chemical::aa_from_oneletter_code( nt_names[m] ) ) );
      for ( Size k = 1; k <= rsd_type.nheavyatoms(); k++ ) {
        std::string atom_name = rsd_type.atom_name( k );
        core::Real sasa_value = 0.0;
        if ( rsd.type().has( atom_name ) ) {
          AtomID atom_id = pose::named_atom_id_to_atom_id( NamedAtomID( atom_name, i ), pose );
          sasa_value = atom_sasa[ atom_id ];
        }
        ObjexxFCL::strip_whitespace(atom_name);
        save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+ "_and_"+atom_name+"_SASA", sasa_value);
      }
    }

    // chi, delta
    for ( Size m = 1; m <= num_nt; m++ ) {
      core::Real chi = is_nt[m] ? pose.chi( i ) : 0.0;
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_chi", chi);
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_is_syn", (chi < 0.0) );
    }
    for ( Size m = 1; m <= num_nt; m++ ) {
      core::Real delta = is_nt[m] ? pose.delta( i ) : 0.0;
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_delta", delta);
      save_feature( feature_names, feature_vals, feature_counter, is_nt_tag[m]+"_and_is_south", ( delta > 120.0) );
    }

    // occlusion of pseudo-methyl at N1 -- towards fitting a potential.
    utility::vector1< Distance > probe_dists = make_vector1( 0.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.5 );
    utility::vector1< Distance > const shells = make_vector1( 0.0, 2.0, 4.0, 6.0, 8.0 );
    //utility::vector1< core::Real > const shells = make_vector1( 0.0, 3.0, 6.0, 9.0 );
    for ( Size m = 1; m <= probe_dists.size(); m++ ) {
      utility::vector1< core::Real > occupancy_densities( (shells.size()-1), 0.0 ); // atoms per A^3.
      core::Real const probe_dist = probe_dists[ m ];
      if ( is_nt[ 1 ] ) {
        core::Vector const probe_xyz = rna_dms_potential.get_probe_xyz( pose.residue( i ), probe_dist );
        rna_dms_potential.get_occupancy_densities( occupancy_densities, pose, i /*for exclusion*/, probe_xyz, shells );
      }
      for ( Size k = 1; k <= occupancy_densities.size(); k++ ) {
        std::string const tag =  is_nt_tag[1]+"_and_pseudomethyldist"+F(3,1,probe_dist)+"_shell_"+I( 1, shells[k] ) + "-" + I( 1, shells[k+1]);
        save_feature( feature_names, feature_vals, feature_counter, tag, occupancy_densities[k] );
      }
    }

    // actual computation of a potential around pseudo-methyl atom.
    vector1< ScoreFunctionOP > probe_scorefxns = make_vector1( rna_dms_potential.get_probe_scorefxn( false /* soft_rep*/, false /* just_fa_atr*/  ),
      rna_dms_potential.get_probe_scorefxn( true, false  ),
      rna_dms_potential.get_probe_scorefxn( true, true ) );
    vector1< std::string > scorefxntags = make_vector1( "hard", "soft", "justatrrep_soft" );
    for ( Size k = 1; k <= probe_scorefxns.size(); k++ ) {
      core::Real pseudo_methyl_plus_oxygen_energy( 0 );
      for ( Size m = 1; m <= probe_dists.size(); m++ ) {
        core::Real const probe_dist = probe_dists[ m ];
        core::Real binding_energy( 0.0 );
        if ( is_nt[ 1 ] ) {
          core::Vector const probe_xyz = rna_dms_potential.get_probe_xyz( pose.residue( i ), probe_dist );
          binding_energy = rna_dms_potential.get_binding_energy( i, probe_xyz, *probe_scorefxns[k] );
        }
        if ( probe_dist == 3.5 || probe_dist == 5.5 ) pseudo_methyl_plus_oxygen_energy += binding_energy;
        std::string const tag =  is_nt_tag[1]+"_and_pseudomethyldist"+F(3,1,probe_dist)+"_"+scorefxntags[k]+"_energy";
        if ( is_nt[ 1 ] ) std::cout << pose.pdb_info()->number( i ) << " " << tag << ": " << binding_energy << std::endl; // some output since this takes so long.
        save_feature( feature_names, feature_vals, feature_counter, tag, binding_energy );
      }

      if ( is_nt[ 1 ] ) std::cout << std::endl;
      std::string const tag =  is_nt_tag[1]+"_and_pseudomethyl_plus_oxygen_"+scorefxntags[k]+"_energy";
      save_feature( feature_names, feature_vals, feature_counter, tag, pseudo_methyl_plus_oxygen_energy );
    }

    if ( num_features == 0 ) num_features = feature_counter; // initialize num_features.
    runtime_assert( feature_vals.size() == num_features ); // sanity check.

    all_feature_vals.push_back( feature_vals );
  }

  runtime_assert( all_feature_vals.size() == res_count );

  rdat.fill_data_from_features( seqchars, resnums, feature_names, all_feature_vals );

  return res_count;
}


///////////////////////////////////////////////
void
rhiju_pdbstats()
{
  using namespace basic::options;
  using namespace basic::options::OptionKeys;
  using namespace core::chemical;
  using namespace core::import_pose;

  vector1 < std::string> pdb_files( option[ in::file::s ]() );
  std::string const file_path( option[ in::path::pdb ]( 1 ) );

  if ( option[ in::file::l ].user() ) {

    std::string const pdb_list(  option[ in::file::l ](1) );
    utility::io::izstream instream( pdb_list );
    if ( !instream ) {
      std::cerr  << "Can't find list file " << pdb_list << std::endl;
      utility::exit( EXIT_FAILURE, __FILE__, __LINE__);
      //return;
    }

    pdb_files.clear();
    std::string pdb_file, line;
    while (  getline( instream, line )  ) {
      std::istringstream line_stream( line );
      line_stream >> pdb_file;
      pdb_files.push_back( pdb_file );
    }

  }

  // later hope to replace this with fa_standard, which should soon include RNA, DNA, & protein.
  ResidueTypeSetCOP rsd_set = core::chemical::ChemicalManager::get_instance()->residue_type_set( "fa_standard" );

  Size count( 0 );
  std::string outfile;
  pose::Pose pose;
  Size total_residues( 0 );

  for ( Size n = 1; n <= pdb_files.size(); n++ ) {

    std::string const pdb_file = pdb_files[n];

    std::string pdb_file_load = pdb_file;
    if ( file_path  != "./" ) pdb_file_load = file_path + '/' + pdb_file;
    pose_from_file( pose, *rsd_set, pdb_file_load , core::import_pose::PDB_file);

    count++;
    std::cout << "Doing input file " << I(4,count) << " ==> " << pdb_file << std::endl;
    std::cout << "Read in pose sequence: " << pose.annotated_sequence() << std::endl;
    pose.dump_pdb( "dump.pdb" );

    if ( option[out::file::o].user() ) outfile  = option[ out::file::o ];
    else outfile = pdb_file + ".rdat";

    io::rna::RDAT rdat;
    rdat.fill_header_information( pose );
    total_residues += rna_features_from_pose( rdat, pose );
    rdat.output_rdat_to_file( outfile );

  }

  std::cout << "FINISHED ==> TOTAL RESIDUES Processed: " << total_residues << std::endl;

}


///////////////////////////////////////////////////////////////
void*
my_main( void* )
{
  rhiju_pdbstats();
  protocols::viewer::clear_conformation_viewers();
  exit( 0 );
}


///////////////////////////////////////////////////////////////////////////////
int
main( int argc, char * argv [] )
{

  try {
    using namespace basic::options;

    core::init::init(argc, argv);

    protocols::viewer::viewer_main( my_main );

  } catch ( utility::excn::EXCN_Base const & e ) {
    std::cout << "caught exception " << e.msg() << std::endl;
    return -1;
  }

}