Implementation of the Ascore For a given peptide sequence and its MS/MS spectrum it identifies the most probable phosphorylation-site(s). For each phosphorylation site a probability score is calculated. The algorithm is implemented according to Beausoleil et al. (Nat. Biotechnol. 2006). More...

#include <OpenMS/ANALYSIS/ID/AScore.h>

Inheritance diagram for AScore:

Public Member Functions
	AScore ()
	Default constructor. More...

	~AScore () override
	Destructor. More...

PeptideHit	compute (const PeptideHit &hit, PeakSpectrum &real_spectrum)
	Computes the AScore and returns all computed phospho-sites. The saved sequences contain only phospho information. All other modifications are dropped due to simplicity. More...

Public Member Functions inherited from DefaultParamHandler
	DefaultParamHandler (const String &name)
	Constructor with name that is displayed in error messages. More...

	DefaultParamHandler (const DefaultParamHandler &rhs)
	Copy constructor. More...

virtual	~DefaultParamHandler ()
	Destructor. More...

virtual DefaultParamHandler &	operator= (const DefaultParamHandler &rhs)
	Assignment operator. More...

virtual bool	operator== (const DefaultParamHandler &rhs) const
	Equality operator. More...

void	setParameters (const Param &param)
	Sets the parameters. More...

const Param &	getParameters () const
	Non-mutable access to the parameters. More...

const Param &	getDefaults () const
	Non-mutable access to the default parameters. More...

const String &	getName () const
	Non-mutable access to the name. More...

void	setName (const String &name)
	Mutable access to the name. More...

const std::vector< String > &	getSubsections () const
	Non-mutable access to the registered subsections. More...

Protected Member Functions
int	compareMZ_ (double mz1, double mz2) const

template<class InputIterator1 , class InputIterator2 , class OutputIterator >
OutputIterator	getSpectrumDifference_ (InputIterator1 first1, InputIterator1 last1, InputIterator2 first2, InputIterator2 last2, OutputIterator result) const

void	computeSiteDeterminingIons_ (const std::vector< PeakSpectrum > &th_spectra, const ProbablePhosphoSites &candidates, std::vector< PeakSpectrum > &site_determining_ions) const
	Computes the site determining_ions for the given AS and sequences in candidates. More...

std::vector< Size >	getSites_ (const AASequence &without_phospho) const
	return all phospho sites More...

std::vector< std::vector< Size > >	computePermutations_ (const std::vector< Size > &sites, Int n_phosphorylation_events) const
	calculate all n_phosphorylation_events sized sets of phospho sites (all versions of the peptides with exactly n_phosphorylation_events) More...

Size	numberOfMatchedIons_ (const PeakSpectrum &th, const PeakSpectrum &windows, Size depth) const
	Computes number of matched ions between windows and the given spectrum. All spectra have to be sorted by position! More...

double	peptideScore_ (const std::vector< double > &scores) const
	Computes the peptide score according to Beausoleil et al. page 1291. More...

void	determineHighestScoringPermutations_ (const std::vector< std::vector< double >> &peptide_site_scores, std::vector< ProbablePhosphoSites > &sites, const std::vector< std::vector< Size >> &permutations, std::multimap< double, Size > &ranking) const
	Finds the peptides with the highest PeptideScores and outputs all information for computing the AScore. More...

double	computeCumulativeScore_ (Size N, Size n, double p) const
	Computes the cumulative binomial probabilities. More...

Size	numberOfPhosphoEvents_ (const String sequence) const
	Computes number of phospho events in a sequence. More...

AASequence	removePhosphositesFromSequence_ (const String sequence) const
	Create variant of the peptide with all phosphorylations removed. More...

std::vector< PeakSpectrum >	createTheoreticalSpectra_ (const std::vector< std::vector< Size >> &permutations, const AASequence &seq_without_phospho) const
	Create theoretical spectra with all combinations with the number of phosphorylation events. More...

std::vector< PeakSpectrum >	peakPickingPerWindowsInSpectrum_ (PeakSpectrum &real_spectrum) const
	Pick top 10 intensity peaks for each 100 Da windows. More...

std::vector< std::vector< double > >	calculatePermutationPeptideScores_ (std::vector< PeakSpectrum > &th_spectra, const std::vector< PeakSpectrum > &windows_top10) const
	Create 10 scores for each theoretical spectrum (permutation), according to Beausoleil et al. Figure 3 b. More...

std::multimap< double, Size >	rankWeightedPermutationPeptideScores_ (const std::vector< std::vector< double >> &peptide_site_scores) const
	Rank weighted permutation scores ascending. More...

void	updateMembers_ () override
	Reimplemented from DefaultParamHandler. More...

Protected Member Functions inherited from DefaultParamHandler
void	defaultsToParam_ ()
	Updates the parameters after the defaults have been set in the constructor. More...

Protected Attributes
double	fragment_mass_tolerance_
	Fragment mass tolerance for spectrum comparisons. More...

bool	fragment_tolerance_ppm_
	Is fragment mass tolerance given in ppm (or Da)? More...

Size	max_peptide_length_
	Limit for peptide lengths that can be analyzed. More...

Size	max_permutations_
	Limit for number of sequence permutations that can be handled. More...

double	unambiguous_score_
	Score for unambiguous assignments (all sites phosphorylated) More...

Protected Attributes inherited from DefaultParamHandler
Param	param_
	Container for current parameters. More...

Param	defaults_
	Container for default parameters. This member should be filled in the constructor of derived classes! More...

std::vector< String >	subsections_
	Container for registered subsections. This member should be filled in the constructor of derived classes! More...

String	error_name_
	Name that is displayed in error messages during the parameter checking. More...

bool	check_defaults_
	If this member is set to false no checking if parameters in done;. More...

bool	warn_empty_defaults_
	If this member is set to false no warning is emitted when defaults are empty;. More...

Friends
struct	PScore

Detailed Description

Implementation of the Ascore For a given peptide sequence and its MS/MS spectrum it identifies the most probable phosphorylation-site(s). For each phosphorylation site a probability score is calculated. The algorithm is implemented according to Beausoleil et al. (Nat. Biotechnol. 2006).

Parameters of this class are:

Name	Type	Default	Restrictions	Description
fragment_mass_tolerance	float	0.05	min: 0	Fragment mass tolerance for spectrum comparisons
fragment_mass_unit	string	Da	Da, ppm	Unit of fragment mass tolerance
max_peptide_length	int	40	min: 0	Restrict scoring to peptides with a length no greater than this value ('0' for 'no restriction')
max_num_perm	int	16384	min: 0	Maximum number of permutations a sequence can have to be processed ('0' for 'no restriction')
unambiguous_score	int	1000		Score to use for unambiguous assignments, where all sites on a peptide are phosphorylated. (Note: If a peptide is not phosphorylated at all, its score is set to '-1'.)

Note:

If a section name is documented, the documentation is displayed as tooltip.
Advanced parameter names are italic.

Constructor & Destructor Documentation

◆ AScore()

AScore ( )

Default constructor.

◆ ~AScore()

~AScore ( )

override

Destructor.

Member Function Documentation

◆ calculatePermutationPeptideScores_()

std::vector<std::vector<double> > calculatePermutationPeptideScores_	(	std::vector< PeakSpectrum > &	th_spectra,
		const std::vector< PeakSpectrum > &	windows_top10
	)		const

protected

Create 10 scores for each theoretical spectrum (permutation), according to Beausoleil et al. Figure 3 b.

◆ compareMZ_()

int compareMZ_	(	double	mz1,
		double	mz2
	)		const

protected

◆ compute()

PeptideHit compute	(	const PeptideHit &	hit,
		PeakSpectrum &	real_spectrum
	)

Computes the AScore and returns all computed phospho-sites. The saved sequences contain only phospho information. All other modifications are dropped due to simplicity.

Parameters

hit	a PeptideHit
real_spectrum	spectrum mapped to hit
fmt	fragment_mass_tolerance, when comparing real_spectrum to a theoretical spectrum of the amino acid sequence of hit.
number_of_phospho_sites	which directs the method to search for this number of phosphorylated sites.

Note: the original sequence is saved in the PeptideHits as MetaValue Search_engine_sequence.

◆ computeCumulativeScore_()

double computeCumulativeScore_	(	Size	N,
		Size	n,
		double	p
	)		const

protected

Computes the cumulative binomial probabilities.

◆ computePermutations_()

std::vector<std::vector<Size> > computePermutations_	(	const std::vector< Size > &	sites,
		Int	n_phosphorylation_events
	)		const

protected

calculate all n_phosphorylation_events sized sets of phospho sites (all versions of the peptides with exactly n_phosphorylation_events)

◆ computeSiteDeterminingIons_()

void computeSiteDeterminingIons_	(	const std::vector< PeakSpectrum > &	th_spectra,
		const ProbablePhosphoSites &	candidates,
		std::vector< PeakSpectrum > &	site_determining_ions
	)		const

protected

Computes the site determining_ions for the given AS and sequences in candidates.

◆ createTheoreticalSpectra_()

std::vector<PeakSpectrum> createTheoreticalSpectra_	(	const std::vector< std::vector< Size >> &	permutations,
		const AASequence &	seq_without_phospho
	)		const

protected

Create theoretical spectra with all combinations with the number of phosphorylation events.

◆ determineHighestScoringPermutations_()

void determineHighestScoringPermutations_	(	const std::vector< std::vector< double >> &	peptide_site_scores,
		std::vector< ProbablePhosphoSites > &	sites,
		const std::vector< std::vector< Size >> &	permutations,
		std::multimap< double, Size > &	ranking
	)		const

protected

Finds the peptides with the highest PeptideScores and outputs all information for computing the AScore.

Note: This function assumes that there are more permutations than the assumed number of phosphorylations!

◆ getSites_()

std::vector<Size> getSites_ ( const AASequence & without_phospho ) const

protected

return all phospho sites

◆ getSpectrumDifference_()

OutputIterator getSpectrumDifference_	(	InputIterator1	first1,
		InputIterator1	last1,
		InputIterator2	first2,
		InputIterator2	last2,
		OutputIterator	result
	)		const

inlineprotected

getSpectrumDifference_ works similar as the method std::set_difference (http://en.cppreference.com/w/cpp/algorithm/set_difference). set_difference was reimplemented, because it was necessary to overwrite the compare operator to be able to compare the m/z values. not implemented as "operator<", because using tolerances for comparison does not imply total ordering

◆ numberOfMatchedIons_()

Size numberOfMatchedIons_	(	const PeakSpectrum &	th,
		const PeakSpectrum &	windows,
		Size	depth
	)		const

protected

Computes number of matched ions between windows and the given spectrum. All spectra have to be sorted by position!

◆ numberOfPhosphoEvents_()

Size numberOfPhosphoEvents_ ( const String sequence ) const

protected

Computes number of phospho events in a sequence.

◆ peakPickingPerWindowsInSpectrum_()

std::vector<PeakSpectrum> peakPickingPerWindowsInSpectrum_ ( PeakSpectrum & real_spectrum ) const

protected

Pick top 10 intensity peaks for each 100 Da windows.

◆ peptideScore_()

double peptideScore_ ( const std::vector< double > & scores ) const

protected

Computes the peptide score according to Beausoleil et al. page 1291.

◆ rankWeightedPermutationPeptideScores_()

std::multimap<double, Size> rankWeightedPermutationPeptideScores_ ( const std::vector< std::vector< double >> & peptide_site_scores ) const

protected

Rank weighted permutation scores ascending.

◆ removePhosphositesFromSequence_()

AASequence removePhosphositesFromSequence_ ( const String sequence ) const

protected

Create variant of the peptide with all phosphorylations removed.

◆ updateMembers_()

void updateMembers_ ( )

overrideprotectedvirtual

Reimplemented from DefaultParamHandler.

Friends And Related Function Documentation

◆ PScore

friend struct PScore

friend

Member Data Documentation

◆ fragment_mass_tolerance_

double fragment_mass_tolerance_

protected

Fragment mass tolerance for spectrum comparisons.

◆ fragment_tolerance_ppm_

bool fragment_tolerance_ppm_

protected

Is fragment mass tolerance given in ppm (or Da)?

◆ max_peptide_length_

Size max_peptide_length_

protected

Limit for peptide lengths that can be analyzed.

◆ max_permutations_

Size max_permutations_

protected

Limit for number of sequence permutations that can be handled.

◆ unambiguous_score_

double unambiguous_score_

protected

Score for unambiguous assignments (all sites phosphorylated)

Public Member Functions

Protected Member Functions

Protected Attributes

Friends

Detailed Description

Constructor & Destructor Documentation

◆ AScore()

◆ ~AScore()

Member Function Documentation

◆ calculatePermutationPeptideScores_()

◆ compareMZ_()

◆ compute()

◆ computeCumulativeScore_()

◆ computePermutations_()

◆ computeSiteDeterminingIons_()

◆ createTheoreticalSpectra_()

◆ determineHighestScoringPermutations_()

◆ getSites_()

◆ getSpectrumDifference_()

◆ numberOfMatchedIons_()

◆ numberOfPhosphoEvents_()

◆ peakPickingPerWindowsInSpectrum_()

◆ peptideScore_()

◆ rankWeightedPermutationPeptideScores_()

◆ removePhosphositesFromSequence_()

◆ updateMembers_()

Friends And Related Function Documentation

◆ PScore

Member Data Documentation

◆ fragment_mass_tolerance_

◆ fragment_tolerance_ppm_

◆ max_peptide_length_

◆ max_permutations_

◆ unambiguous_score_