libopenms-dev 1.11.1-3 / usr / include / OpenMS / CHEMISTRY / EnzymaticDigestion.h

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// $Maintainer: Chris Bielow $
// $Authors: Marc Sturm, Chris Bielow $
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#ifndef OPENMS_CHEMISTRY_ENZYMATICDIGESTION_H
#define OPENMS_CHEMISTRY_ENZYMATICDIGESTION_H

#include <OpenMS/CONCEPT/Types.h>
#include <OpenMS/CHEMISTRY/AASequence.h>

#include <string>
#include <vector>

namespace OpenMS
{
  /**
       @brief Class for the enzymatic digestion of proteins

   Digestion can be performed using simple regular expressions,
   e.g. [KR] | [^P]
   for trypsin. Also missed cleavages can be modelled, i.e. adjacent peptides are not cleaved
   due to enzyme malfunction/access restrictions. If @em n missed cleavages are given, all possible resulting
   peptides (cleaved and uncleaved) with up to @em n missed cleavages are returned.
   Thus @b no random selection of just @em n specific missed cleavage sites is performed.

   An alternative model is also available, where the protein is cleaved only at positions where a cleavage model
   trained on real data, exceeds a certain threshold. The model is published in
   Siepen et al. (2007), "Prediction of missed cleavage sites in tryptic peptides aids protein identification in proteomics.", doi: 10.1021/pr060507u
   The model is only available for trypsin and ignores the missed cleavage setting. You should however use setLogThreshold()
   to adjust FP vs FN rates. A higher threshold increases the number of cleavages predicted.

       @ingroup Chemistry
  */
  class OPENMS_DLLAPI EnzymaticDigestion
  {
public:
    /// Possible enzymes for the digestion (adapt NamesOfEnzymes & nextCleavageSite_() if you add more enzymes here)
    enum Enzyme
    {
      ENZYME_TRYPSIN,
      SIZE_OF_ENZYMES
    };
    /// Names of the Enzymes
    static const std::string NamesOfEnzymes[SIZE_OF_ENZYMES];

    /// when querying for valid digestion products, this determines if the specificity of the two peptide ends is considered important
    enum Specificity
    {
      SPEC_FULL,    //< fully enzyme specific, e.g., tryptic (ends with KR, AA-before is KR), or peptide is at protein terminal ends
      SPEC_SEMI,    //< semi specific, i.e., one of the two cleavage sites must fulfill requirements
      SPEC_NONE,    //< no requirements on start / end
      SIZE_OF_SPECIFICITY
    };
    /// Names of the Specificity
    static const std::string NamesOfSpecificity[SIZE_OF_SPECIFICITY];


    /// Default constructor
    EnzymaticDigestion();

    /// Copy constructor
    EnzymaticDigestion(const EnzymaticDigestion& rhs);

    /// Assignment operator
    EnzymaticDigestion& operator=(const EnzymaticDigestion& rhs);


    /// Returns the number of missed cleavages for the digestion
    SignedSize getMissedCleavages() const;

    /// Sets the number of missed cleavages for the digestion (default is 0). This setting is ignored when log model is used.
    void setMissedCleavages(SignedSize missed_cleavages);

    /// Returns the enzyme for the digestion
    Enzyme getEnzyme() const;

    /// Sets the enzyme for the digestion (default is ENZYME_TRYPSIN).
    void setEnzyme(Enzyme enzyme);
    
    /// convert enzyme string name to enum
    /// returns SIZE_OF_ENZYMES if @p name is not valid
    static Enzyme getEnzymeByName(const String & name);

    /// Returns the specificity for the digestion
    Specificity getSpecificity() const;

    /// Sets the specificity for the digestion (default is SPEC_FULL).
    void setSpecificity(Specificity spec);

    /// convert spec string name to enum
    /// returns SIZE_OF_SPECIFICITY if @p name is not valid
    static Specificity getSpecificityByName(const String & name);

    /// Performs the enzymatic digestion of a protein.
    void digest(const AASequence & protein, std::vector<AASequence> & output) const;

    /// Returns the number of peptides a digestion of @p protein would yield under the current enzyme and missed cleavage settings.
    Size peptideCount(const AASequence & protein);

    /// use trained model when digesting?
    bool isLogModelEnabled() const;

    /// enables/disabled the trained model
    void setLogModelEnabled(bool enabled);

    /// Returns the threshold which needs to be exceeded to call a cleavage (only for the trained cleavage model on real data)
    DoubleReal getLogThreshold() const;

    /// Sets the threshold which needs to be exceeded to call a cleavage (only for the trained cleavage model on real data)
    /// Default is 0.25
    void setLogThreshold(DoubleReal threshold);

    /// Returns true if peptide at position @p pep_pos with length @p pep_length within protein @p protein was generated by the current model
    bool isValidProduct(const AASequence& protein, Size pep_pos, Size pep_length);

protected:
    // define a binding site by position and AA
    struct BindingSite
    {
      Size position;
      String AAname;

      BindingSite() :
        position(), AAname() {}

      BindingSite(const Size & p, const String & name) :
        position(p), AAname(name) {}

      bool operator<(const BindingSite & rhs) const
      {
        return (position < rhs.position) || ((position == rhs.position) && (AAname < rhs.AAname));
      }

      bool operator==(const BindingSite & rhs) const
      {
        return position == rhs.position && AAname == rhs.AAname;
      }

    };

    // define the log likelihood for missed and cleavage model
    struct CleavageModel
    {
      DoubleReal p_cleave;
      DoubleReal p_miss;

      CleavageModel() :
        p_cleave(0), p_miss(0) {}
      CleavageModel(const DoubleReal & p_c, const DoubleReal & p_m) :
        p_cleave(p_c), p_miss(p_m) {}
    };

    /// moves the iterator @p p behind (i.e., C-term) the next cleavage site of the @p sequence
    void nextCleavageSite_(const AASequence & sequence, AASequence::ConstIterator & p) const;

    /// tests if position pointed to by @p p (N-term side) is a valid cleavage site
    bool isCleavageSite_(const AASequence & sequence, const AASequence::ConstIterator & p) const;

    /// Number of missed cleavages
    SignedSize missed_cleavages_;
    /// Used enzyme
    Enzyme enzyme_;
    /// specificity of enzyme
    Specificity specificity_;

    /// use the log model or naive digestion (with missed cleavages)
    bool use_log_model_;
    /// Threshold to decide if position is cleaved or missed (only for the model)
    DoubleReal log_model_threshold_;
    /// Holds the cleavage model
    Map<BindingSite, CleavageModel> model_data_;
  };

} // namespace OpenMS

#endif // OPENMS_CHEMISTRY_ENZYMATICDIGESTION_H