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/*
* Hypermutationglobalerrorrate.h
*
* Created on: Mar 8, 2016
* Author: Quentin Marcou
*
* This source code is distributed as part of the IGoR software.
* IGoR (Inference and Generation of Repertoires) is a versatile software to analyze and model immune receptors
* generation, selection, mutation and all other processes.
* Copyright (C) 2017 Quentin Marcou
*
* This program is free software: you can redistribute it and/or modify
* it under the terms of the GNU 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 General Public License for more details.
* You should have received a copy of the GNU General Public License
* along with this program. If not, see <https://www.gnu.org/licenses/>.
*
*/
#ifndef HYPERMUTATIONGLOBALERRORRATE_H_
#define HYPERMUTATIONGLOBALERRORRATE_H_
#include "Errorrate.h"
#include "Genechoice.h"
#include "Deletion.h"
#include <algorithm>
#include <array>
#include <math.h>
#include <gsl/gsl_linalg.h>
#include <gsl/gsl_vector.h>
#include <gsl/gsl_blas.h>
#include <memory>
/**
* \class Hypermutation_global_errorrate Hypermutationglobalerrorrate.h
* \brief An additive (independent site) context dependent hypermutation model.
* \author Q.Marcou
* \version 1.0
*
* A specialization of the ErrorRate class.
* Implements a context dependent hypermutation/error model with tunable context size.
* Nucleotide from the context are assumed to contribute independently to the mutability of the context through an additive logarithmic score.
* Such a model contains only 3N+1 parameters and allows to probe large context sizes.
* The identity of the resulting nucleotide after mutation is assumed to follow a uniform distribution.
*/
class Hypermutation_global_errorrate: public Error_rate {
public:
Hypermutation_global_errorrate(size_t,Gene_class,Gene_class,double);
Hypermutation_global_errorrate(size_t,Gene_class,Gene_class,double,std::vector<double>);
Hypermutation_global_errorrate(size_t,Gene_class,Gene_class,double,std::string);
Hypermutation_global_errorrate(size_t,Gene_class,Gene_class,double,std::vector<double>,std::string);
//Hypermutation_global_errorrate(size_t,Gene_class,Gene_class, ??); Constructor to read or copy the error rate
virtual ~Hypermutation_global_errorrate();
double compare_sequences_error_prob( double ,const std::string& , Seq_type_str_p_map& , const Seq_offsets_map& , const std::unordered_map<std::tuple<Event_type,Gene_class,Seq_side>, std::shared_ptr<Rec_Event>>& , Mismatch_vectors_map& , double& , double& );
void update();
void initialize(const std::unordered_map<std::tuple<Event_type,Gene_class,Seq_side>, std::shared_ptr<Rec_Event>>&);
void add_to_norm_counter();
void clean_seq_counters();
void clean_all_counters();
void write2txt(std::ofstream&);
void set_output_Nmer_stream(std::string);
std::shared_ptr<Error_rate> copy()const;
std::string type() const {return "HypermutationGlobalErrorRate";}
Hypermutation_global_errorrate& operator+=(Hypermutation_global_errorrate);
Error_rate* add_checked (Error_rate*);
const double& get_err_rate_upper_bound(size_t,size_t) ;
void build_upper_bound_matrix(size_t,size_t);
int get_number_non_zero_likelihood_seqs() const{return number_seq;};
std::queue<int> generate_errors(std::string& , std::mt19937_64&) const;
uint64_t generate_random_contributions(double);
private:
void update_Nmers_proba(int,int,double);
//void compute_P_SHM_and_BG();
double compute_Nmer_unorm_score(int*,double*);
double compute_new_model_likelihood(double,gsl_vector*);
void increment_base_10_and_4(int& , int*);
void introduce_uniform_transversion(char&, std::mt19937_64& , std::uniform_real_distribution<double>&) const;
Gene_class learn_on;
Gene_class apply_to;
size_t mutation_Nmer_size;
//std::unique_ptr<double[]> ei_nucleotide_contributions;
double* ei_nucleotide_contributions;
double mu;
//std::map<int,double> Nmer_background_proba;
double* Nmer_mutation_proba;
/* double* Nmer_P_SHM;
double* Nmer_P_BG;*/
size_t alphabet_size = 4;
//std::map<int,double> Nmer_background_proba_count;
//std::map<int,double> Nmer_SHM_proba_count;
//Normalized coverage and error counters
//# V D and J possible realizations
std::shared_ptr<Gene_choice> v_gene_event_p;
size_t n_v_real;
std::unordered_map<std::string , Event_realization> v_realizations;
std::shared_ptr<Gene_choice> d_gene_event_p;
size_t n_d_real;
std::unordered_map<std::string , Event_realization> d_realizations;
std::shared_ptr<Gene_choice> j_gene_event_p;
size_t n_j_real;
std::unordered_map<std::string , Event_realization> j_realizations;
double* one_seq_Nmer_N_SHM;
double* one_seq_Nmer_N_bg;
double* Nmer_N_SHM;
double* Nmer_N_bg;
Int_Str* v_sequences;
Int_Str* j_sequences;
bool apply_to_v;
bool apply_to_d;
bool apply_to_j;
bool learn_on_v;
bool learn_on_d;
bool learn_on_j;
bool v_gene;
bool d_gene;
bool j_gene;
bool vd_ins;
bool dj_ins;
bool vj_ins;
const int** vgene_offset_p;
const int** dgene_offset_p;
const int** jgene_offset_p;
const int** vgene_real_index_p;
const int** dgene_real_index_p;
const int** jgene_real_index_p;
//Get deletion values
//TODO need to change this in order to handle multiple models
const int* v_3_del_value_p;
const int* d_5_del_value_p;
const int* d_3_del_value_p;
const int* j_5_del_value_p;
const int no_del_buffer = 0; //buffer used in case of no deletion event
//Utility speed variables
mutable int i;//iteration utility
mutable int j;
int v_3_del_value_corr;//Corrected value for deletion numbers to avoid taking into account negative deletions
int d_5_del_value_corr;
int d_3_del_value_corr;
int j_5_del_value_corr;
mutable double* tmp_cov_p;
mutable double* tmp_err_p;
int tmp_corr_len;
int tmp_len_util;
double scenario_new_proba;
Int_Str scenario_resulting_sequence;
std::vector<size_t> adressing_vector;
mutable std::queue<size_t> current_Nmer;
size_t largest_nuc_adress;
mutable int tmp_int_nt;
mutable int Nmer_index;
std::vector<int>::const_iterator current_mismatch;
bool is_visible_nt;
std::vector<int> empty_vec_util;
std::vector<int>* vec_ptr_util;
double* debug_v_seq_coverage;
double* debug_mismatch_seq_coverage;
std::string debug_current_string;
std::shared_ptr<std::ofstream> output_Nmer_stat_stream;
bool output_Nmer_stat;
};
#endif /* HYPERMUTATIONGLOBALERRORRATE_H_ */
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