#ifndef __VIENNA_RNA_PACKAGE_PART_FUNC_H__
#define __VIENNA_RNA_PACKAGE_PART_FUNC_H__
#include "data_structures.h"
#ifdef __GNUC__
#define DEPRECATED(func) func __attribute__ ((deprecated))
#else
#define DEPRECATED(func) func
#endif
/**
* \addtogroup pf_fold
* \brief This section provides information about all functions and variables related to
* the calculation of the partition function and base pair probabilities.
*
* Instead of the minimum free energy structure the partition function of all possible structures
* and from that the pairing probability for every possible pair can be calculated, using a dynamic
* programming algorithm as described in \cite mccaskill:1990.
*
* @{
* \file part_func.h
* \brief Partition function of single RNA sequences
*
* This file includes (almost) all function declarations within the <b>RNAlib</b> that are related to
* Partion function folding...
* @}
*/
/**
* \brief Flag indicating that auxilary arrays are needed throughout the computations. This is essential for stochastic backtracking
*
* Set this variable to 1 prior to a call of pf_fold() to ensure that all matrices needed for stochastic backtracking
* are filled in the forward recursions
*
* \ingroup subopt_stochbt
*
* \see pbacktrack(), pbacktrack_circ
*/
extern int st_back;
/*
#################################################
# PARTITION FUNCTION COMPUTATION #
#################################################
*/
/**
* \brief Compute the partition function \f$Q\f$ for a given RNA sequence
*
* If \a structure is not a NULL pointer on input, it contains on
* return a string consisting of the letters " . , | { } ( ) " denoting
* bases that are essentially unpaired, weakly paired, strongly paired without
* preference, weakly upstream (downstream) paired, or strongly up-
* (down-)stream paired bases, respectively.
* If #fold_constrained is not 0, the \a structure string is
* interpreted on input as a list of constraints for the folding. The
* character "x" marks bases that must be unpaired, matching brackets " ( ) "
* denote base pairs, all other characters are ignored. Any pairs
* conflicting with the constraint will be forbidden. This is usually sufficient
* to ensure the constraints are honored.
* If tha parameter calculate_bppm is set to 0 base pairing probabilities will not
* be computed (saving CPU time), otherwise after calculations took place #pr will
* contain the probability that bases \a i and \a j pair.
*
* \ingroup pf_fold
*
* \note The global array #pr is deprecated and the user who wants the calculated
* base pair probabilities for further computations is advised to use the function
* export_bppm()
* \post After successful run the hidden folding matrices are filled with the appropriate Boltzmann factors.
* Depending on whether the global variable #do_backtrack was set the base pair probabilities are already
* computed and may be accessed for further usage via the export_bppm() function.
* A call of free_pf_arrays() will free all memory allocated by this function.
* Successive calls will first free previously allocated memory before starting the computation.
* \see pf_fold(), pf_circ_fold(), bppm_to_structure(), export_bppm(), get_boltzmann_factors(), free_pf_arrays()
* \param[in] sequence The RNA sequence input
* \param[in,out] structure A pointer to a char array where a base pair probability information can be stored in a
* pseudo-dot-bracket notation (may be NULL, too)
* \param[in] parameters Data structure containing the precalculated Boltzmann factors
* \param[in] calculate_bppm Switch to Base pair probability calculations on/off (0==off)
* \param[in] is_constrained Switch to indicate that a structure contraint is passed via the structure argument (0==off)
* \param[in] is_circular Switch to (de-)activate postprocessing steps in case RNA sequence is circular (0==off)
* \return The Gibbs free energy of the ensemble (\f$G = -RT \cdot \log(Q) \f$) in kcal/mol
*/
float pf_fold_par( const char *sequence,
char *structure,
pf_paramT *parameters,
int calculate_bppm,
int is_constrained,
int is_circular);
/**
* \brief Compute the partition function \f$Q\f$ of an RNA sequence
*
* If \a structure is not a NULL pointer on input, it contains on
* return a string consisting of the letters " . , | { } ( ) " denoting
* bases that are essentially unpaired, weakly paired, strongly paired without
* preference, weakly upstream (downstream) paired, or strongly up-
* (down-)stream paired bases, respectively.
* If #fold_constrained is not 0, the \a structure string is
* interpreted on input as a list of constraints for the folding. The
* character "x" marks bases that must be unpaired, matching brackets " ( ) "
* denote base pairs, all other characters are ignored. Any pairs
* conflicting with the constraint will be forbidden. This is usually sufficient
* to ensure the constraints are honored.
* If #do_backtrack has been set to 0 base pairing probabilities will not
* be computed (saving CPU time), otherwise #pr will contain the probability
* that bases \a i and \a j pair.
*
* \ingroup pf_fold
*
* \note The global array #pr is deprecated and the user who wants the calculated
* base pair probabilities for further computations is advised to use the function
* export_bppm().
* \note \b OpenMP:
* This function is not entirely threadsafe. While the recursions are working on their
* own copies of data the model details for the recursions are determined from the global
* settings just before entering the recursions. Consider using pf_fold_par() for a
* really threadsafe implementation.
* \pre This function takes its model details from the global variables provided in \e RNAlib
* \post After successful run the hidden folding matrices are filled with the appropriate Boltzmann factors.
* Depending on whether the global variable #do_backtrack was set the base pair probabilities are already
* computed and may be accessed for further usage via the export_bppm() function.
* A call of free_pf_arrays() will free all memory allocated by this function.
* Successive calls will first free previously allocated memory before starting the computation.
* \see pf_fold_par(), pf_circ_fold(), bppm_to_structure(), export_bppm()
* \param sequence The RNA sequence input
* \param structure A pointer to a char array where a base pair probability information can be stored in a pseudo-dot-bracket notation (may be NULL, too)
* \return The Gibbs free energy of the ensemble (\f$G = -RT \cdot \log(Q) \f$) in kcal/mol
*/
float pf_fold(const char *sequence,
char *structure);
/**
* \brief Compute the partition function of a circular RNA sequence
*
* \ingroup pf_fold
*
* \note The global array #pr is deprecated and the user who wants the calculated
* base pair probabilities for further computations is advised to use the function
* export_bppm().
* \note \b OpenMP:
* This function is not entirely threadsafe. While the recursions are working on their
* own copies of data the model details for the recursions are determined from the global
* settings just before entering the recursions. Consider using pf_fold_par() for a
* really threadsafe implementation.
* \pre This function takes its model details from the global variables provided in \e RNAlib
* \post After successful run the hidden folding matrices are filled with the appropriate Boltzmann factors.
* Depending on whether the global variable #do_backtrack was set the base pair probabilities are already
* computed and may be accessed for further usage via the export_bppm() function.
* A call of free_pf_arrays() will free all memory allocated by this function.
* Successive calls will first free previously allocated memory before starting the computation.
* \see pf_fold_par(), pf_fold()
* \param[in] sequence The RNA sequence input
* \param[in,out] structure A pointer to a char array where a base pair probability information can be
* stored in a pseudo-dot-bracket notation (may be NULL, too)
* \return The Gibbs free energy of the ensemble (\f$G = -RT \cdot \log(Q) \f$) in kcal/mol
*/
float pf_circ_fold( const char *sequence,
char *structure);
/**
* \brief Sample a secondary structure from the Boltzmann ensemble according its probability\n
*
* \ingroup subopt_stochbt
* \pre pf_fold_par() or pf_fold() have to be called first to fill the partition function matrices
*
* \param sequence The RNA sequence
* \return A sampled secondary structure in dot-bracket notation
*/
char *pbacktrack(char *sequence);
/**
* \brief Sample a secondary structure of a circular RNA from the Boltzmann ensemble according its probability
*
* This function does the same as \ref pbacktrack() but assumes the RNA molecule to be circular
*
* \ingroup subopt_stochbt
* \pre pf_fold_par() or pf_fold_circ() have to be called first to fill the partition function matrices
*
* \param sequence The RNA sequence
* \return A sampled secondary structure in dot-bracket notation
*/
char *pbacktrack_circ(char *sequence);
/**
* \brief Free arrays for the partition function recursions
*
* Call this function if you want to free all allocated memory associated with
* the partition function forward recursion.
* \note Successive calls of pf_fold(), pf_circ_fold() already check if they should free
* any memory from a previous run.
* \note <b>OpenMP notice:</b><br>
* This function should be called before leaving a thread in order to avoid leaking memory
*
* \ingroup pf_fold
*
* \post All memory allocated by pf_fold_par(), pf_fold() or pf_circ_fold() will be free'd
* \see pf_fold_par(), pf_fold(), pf_circ_fold()
*/
void free_pf_arrays(void);
/**
* \brief Recalculate energy parameters
*
* Call this function to recalculate the pair matrix and energy parameters
* after a change in folding parameters like #temperature
*
* \ingroup pf_fold
*
*/
void update_pf_params(int length);
/**
* \brief Recalculate energy parameters
*
* \ingroup pf_fold
*
*/
void update_pf_params_par(int length, pf_paramT *parameters);
/**
* \brief Get a pointer to the base pair probability array
* \ingroup pf_fold
*
* Accessing the base pair probabilities for a pair (i,j) is achieved by
* \code
* FLT_OR_DBL *pr = export_bppm();
* pr_ij = pr[iindx[i]-j];
* \endcode
*
* \pre Call pf_fold_par(), pf_fold() or pf_circ_fold() first to fill the base pair probability array
*
* \see pf_fold(), pf_circ_fold(), get_iindx()
*
* \return A pointer to the base pair probability array
*/
FLT_OR_DBL *export_bppm(void);
/*
#################################################
# OTHER PARTITION FUNCTION RELATED DECLARATIONS #
#################################################
*/
/**
* \brief Create a plist from a probability matrix
*
* The probability matrix given is parsed and all pair probabilities above
* the given threshold are used to create an entry in the plist
*
* The end of the plist is marked by sequence positions i as well as j
* equal to 0. This condition should be used to stop looping over its
* entries
*
* \note This function is threadsafe
* \ingroup pf_fold
* \param[out] pl A pointer to the plist that is to be created
* \param[in] probs The probability matrix used for creting the plist
* \param[in] length The length of the RNA sequence
* \param[in] cutoff The cutoff value
*/
void assign_plist_from_pr( plist **pl,
FLT_OR_DBL *probs,
int length,
double cutoff);
/* this doesn't work if free_pf_arrays() is called before */
void assign_plist_gquad_from_pr(plist **pl,
int length,
double cut_off);
char *get_centroid_struct_gquad_pr(int length,
double *dist);
/**
* \brief Get the pointers to (almost) all relavant computation arrays used in partition function computation
*
* \ingroup pf_fold
* \pre In order to assign meaningful pointers, you have to call pf_fold_par() or pf_fold() first!
* \see pf_fold_par(), pf_fold(), pf_circ_fold()
* \param[out] S_p A pointer to the 'S' array (integer representation of nucleotides)
* \param[out] S1_p A pointer to the 'S1' array (2nd integer representation of nucleotides)
* \param[out] ptype_p A pointer to the pair type matrix
* \param[out] qb_p A pointer to the Q<sup>B</sup> matrix
* \param[out] qm_p A pointer to the Q<sup>M</sup> matrix
* \param[out] q1k_p A pointer to the 5' slice of the Q matrix (\f$q1k(k) = Q(1, k)\f$)
* \param[out] qln_p A pointer to the 3' slice of the Q matrix (\f$qln(l) = Q(l, n)\f$)
* \return Non Zero if everything went fine, 0 otherwise
*/
int get_pf_arrays(short **S_p,
short **S1_p,
char **ptype_p,
FLT_OR_DBL **qb_p,
FLT_OR_DBL **qm_p,
FLT_OR_DBL **q1k_p,
FLT_OR_DBL **qln_p);
/**
* \brief Get the free energy of a subsequence from the q[] array
*/
double get_subseq_F(int i, int j);
/**
* \brief Get the centroid structure of the ensemble
*
* This function is a threadsafe replacement for \ref centroid() with a 'plist' input
*
* The centroid is the structure with the minimal average distance to all other structures
* \n \f$ <d(S)> = \sum_{(i,j) \in S} (1-p_{ij}) + \sum_{(i,j) \notin S} p_{ij} \f$ \n
* Thus, the centroid is simply the structure containing all pairs with \f$p_ij>0.5\f$
* The distance of the centroid to the ensemble is written to the memory adressed by \a dist.
*
* \ingroup centroid_fold
* \param[in] length The length of the sequence
* \param[out] dist A pointer to the distance variable where the centroid distance will be written to
* \param[in] pl A pair list containing base pair probability information about the ensemble
* \return The centroid structure of the ensemble in dot-bracket notation
*/
char *get_centroid_struct_pl(int length,
double *dist,
plist *pl);
/**
* \brief Get the centroid structure of the ensemble
*
* This function is a threadsafe replacement for \ref centroid() with a probability array input
*
* The centroid is the structure with the minimal average distance to all other structures
* \n \f$ <d(S)> = \sum_{(i,j) \in S} (1-p_{ij}) + \sum_{(i,j) \notin S} p_{ij} \f$ \n
* Thus, the centroid is simply the structure containing all pairs with \f$p_ij>0.5\f$
* The distance of the centroid to the ensemble is written to the memory adressed by \a dist.
*
* \ingroup centroid_fold
* \param[in] length The length of the sequence
* \param[out] dist A pointer to the distance variable where the centroid distance will be written to
* \param[in] pr A upper triangular matrix containing base pair probabilities (access via iindx \ref get_iindx() )
* \return The centroid structure of the ensemble in dot-bracket notation
*/
char *get_centroid_struct_pr(int length,
double *dist,
FLT_OR_DBL *pr);
/**
* \brief Get the mean base pair distance of the last partition function computation
*
* \note To ensure thread-safety, use the function mean_bp_distance_pr() instead!
*
* \ingroup pf_fold
*
* \see mean_bp_distance_pr()
*
* \param length
* \return mean base pair distance in thermodynamic ensemble
*/
double mean_bp_distance(int length);
/**
* \brief Get the mean base pair distance in the thermodynamic ensemble
*
* This is a threadsafe implementation of \ref mean_bp_dist() !
*
* \f$<d> = \sum_{a,b} p_a p_b d(S_a,S_b)\f$\n
* this can be computed from the pair probs \f$p_ij\f$ as\n
* \f$<d> = \sum_{ij} p_{ij}(1-p_{ij})\f$
*
* \note This function is threadsafe
*
* \ingroup pf_fold
*
* \param length The length of the sequence
* \param pr The matrix containing the base pair probabilities
* \return The mean pair distance of the structure ensemble
*/
double mean_bp_distance_pr(int length,
FLT_OR_DBL *pr);
/**
* \brief Create a dot-bracket like structure string from base pair probability matrix
*/
void bppm_to_structure(char *structure,
FLT_OR_DBL *pr,
unsigned int length);
plist *stackProb(double cutoff);
/**
* \brief Get a pseudo dot bracket notation for a given probability information
*/
char bppm_symbol(const float *x);
/*
#################################################
# DEPRECATED FUNCTIONS #
#################################################
*/
/**
* \brief Allocate space for pf_fold()
*
* \deprecated This function is obsolete and will be removed soon!
*/
DEPRECATED(void init_pf_fold(int length));
/**
* \deprecated This function is deprecated and should not be used anymore as it is not threadsafe!
* \see get_centroid_struct_pl(), get_centroid_struct_pr()
*/
DEPRECATED(char *centroid(int length,
double *dist)); /* mean pair distance of ensemble */
/**
* get the mean pair distance of ensemble
*
* \deprecated This function is not threadsafe and should not be used anymore. Use \ref mean_bp_distance() instead!
*/
DEPRECATED(double mean_bp_dist(int length));
/**
* \deprecated Use \ref exp_E_IntLoop() from loop_energies.h instead
*/
DEPRECATED(double expLoopEnergy(int u1,
int u2,
int type,
int type2,
short si1,
short sj1,
short sp1,
short sq1));
/**
* \deprecated Use exp_E_Hairpin() from loop_energies.h instead
*/
DEPRECATED(double expHairpinEnergy( int u,
int type,
short si1,
short sj1,
const char *string));
#endif