Generate assays from a TargetedExperiment. More...

#include <OpenMS/ANALYSIS/OPENSWATH/MRMAssay.h>

Inheritance diagram for MRMAssay:

Public Types
typedef std::vector< OpenMS::TargetedExperiment::Protein >	ProteinVectorType

typedef std::vector< OpenMS::TargetedExperiment::Peptide >	PeptideVectorType

typedef std::vector< OpenMS::TargetedExperiment::Compound >	CompoundVectorType

typedef std::vector< OpenMS::ReactionMonitoringTransition >	TransitionVectorType

typedef std::map< String, std::vector< const ReactionMonitoringTransition * > >	PeptideTransitionMapType

typedef std::map< String, std::vector< const ReactionMonitoringTransition * > >	CompoundTransitionMapType

typedef boost::unordered_map< String, std::set< std::string > >	ModifiedSequenceMap
	Maps an unmodified sequence to all its modified sequences. More...

typedef boost::unordered_map< size_t, ModifiedSequenceMap >	SequenceMapT
	Stores the ModifiedSequenceMap for all SWATH windows. More...

typedef std::vector< std::pair< double, std::string > >	FragmentSeqMap
	Describes a fragment sequence map of : "fragment m/z" -> "modified sequence". More...

typedef boost::unordered_map< size_t, boost::unordered_map< String, FragmentSeqMap > >	IonMapT
	Stores a mapping : "unmodified sequence" -> FragmentSeqMap for all SWATH windows. More...

typedef std::vector< std::pair< std::string, double > >	IonSeries
	Describes an ion series: "ion_type" -> "fragment m/z". More...

typedef std::map< String, IonSeries >	PeptideMapT
	Maps a peptide sequence to an ion series: "ion_type" -> "fragment m/z". More...

typedef boost::unordered_map< String, TargetedExperiment::Peptide >	TargetDecoyMapT
	Maps the peptide id (same for target and decoy) to the decoy peptide object. More...

Public Types inherited from ProgressLogger
enum	LogType { CMD, GUI, NONE }
	Possible log types. More...

Public Member Functions
	MRMAssay ()
	Constructor. More...

	~MRMAssay ()
	Destructor. More...

void	reannotateTransitions (OpenMS::TargetedExperiment &exp, double precursor_mz_threshold, double product_mz_threshold, const std::vector< String > &fragment_types, const std::vector< size_t > &fragment_charges, bool enable_specific_losses, bool enable_unspecific_losses, int round_decPow=-4)
	Annotates and filters transitions in a TargetedExperiment. More...

void	restrictTransitions (OpenMS::TargetedExperiment &exp, double lower_mz_limit, double upper_mz_limit, const std::vector< std::pair< double, double > > &swathes)
	Restrict and filter transitions in a TargetedExperiment. More...

void	detectingTransitions (OpenMS::TargetedExperiment &exp, int min_transitions, int max_transitions)
	Select detecting fragment ions. More...

void	detectingTransitionsCompound (OpenMS::TargetedExperiment &exp, int min_transitions, int max_transitions)
	Filters transitions by intensity, only keeping the top N transitions. More...

void	uisTransitions (OpenMS::TargetedExperiment &exp, const std::vector< String > &fragment_types, const std::vector< size_t > &fragment_charges, bool enable_specific_losses, bool enable_unspecific_losses, bool enable_ms2_precursors, double mz_threshold, const std::vector< std::pair< double, double > > &swathes, int round_decPow=-4, size_t max_num_alternative_localizations=20, int shuffle_seed=-1, bool disable_decoy_transitions=false)
	Annotate UIS / site-specific transitions. More...

Public Member Functions inherited from ProgressLogger
	ProgressLogger ()
	Constructor. More...

	~ProgressLogger ()
	Destructor. More...

	ProgressLogger (const ProgressLogger &other)
	Copy constructor. More...

ProgressLogger &	operator= (const ProgressLogger &other)
	Assignment Operator. More...

void	setLogType (LogType type) const
	Sets the progress log that should be used. The default type is NONE! More...

LogType	getLogType () const
	Returns the type of progress log being used. More...

void	startProgress (SignedSize begin, SignedSize end, const String &label) const
	Initializes the progress display. More...

void	setProgress (SignedSize value) const
	Sets the current progress. More...

void	endProgress () const
	Ends the progress display. More...

void	nextProgress () const
	increment progress by 1 (according to range begin-end) More...

Protected Member Functions
std::vector< std::string >	getMatchingPeptidoforms_ (const double fragment_ion, const FragmentSeqMap &ions, const double mz_threshold)
	Check whether fragment ion are unique ion signatures in vector within threshold and return matching peptidoforms. More...

int	getSwath_ (const std::vector< std::pair< double, double > > &swathes, const double precursor_mz)
	Get swath index (precursor isolation window ordinal) for a particular precursor. More...

bool	isInSwath_ (const std::vector< std::pair< double, double > > &swathes, const double precursor_mz, const double product_mz)
	Check whether the product m/z of a transition falls into the precursor isolation window. More...

std::string	getRandomSequence_ (size_t sequence_size, boost::variate_generator< boost::mt19937 &, boost::uniform_int<> > pseudoRNG)
	Generates random peptide sequence. More...

std::vector< std::vector< size_t > >	nchoosekcombinations_ (const std::vector< size_t > &n, size_t k)
	Computes all N choose K combinations. More...

std::vector< OpenMS::AASequence >	addModificationsSequences_ (const std::vector< OpenMS::AASequence > &sequences, const std::vector< std::vector< size_t > > &mods_combs, const OpenMS::String &modification)
	Generate modified peptide forms based on all possible combinations. More...

std::vector< OpenMS::AASequence >	generateTheoreticalPeptidoforms_ (const OpenMS::AASequence &sequence)
	Generate alternative modified peptide forms according to ModificationsDB. More...

std::vector< OpenMS::AASequence >	generateTheoreticalPeptidoformsDecoy_ (const OpenMS::AASequence &sequence, const OpenMS::AASequence &decoy_sequence)
	Generate alternative modified peptide forms according to ModificationsDB. More...

void	generateTargetInSilicoMap_ (const OpenMS::TargetedExperiment &exp, const std::vector< String > &fragment_types, const std::vector< size_t > &fragment_charges, bool enable_specific_losses, bool enable_unspecific_losses, bool enable_ms2_precursors, const std::vector< std::pair< double, double > > &swathes, int round_decPow, size_t max_num_alternative_localizations, SequenceMapT &TargetSequenceMap, IonMapT &TargetIonMap, PeptideMapT &TargetPeptideMap)
	Generate target in silico map. More...

void	generateDecoySequences_ (const SequenceMapT &TargetSequenceMap, boost::unordered_map< String, String > &DecoySequenceMap, int shuffle_seed)
	Generate decoy sequences. More...

void	generateDecoyInSilicoMap_ (const OpenMS::TargetedExperiment &exp, const std::vector< String > &fragment_types, const std::vector< size_t > &fragment_charges, bool enable_specific_losses, bool enable_unspecific_losses, bool enable_ms2_precursors, const std::vector< std::pair< double, double > > &swathes, int round_decPow, TargetDecoyMapT &TargetDecoyMap, PeptideMapT &TargetPeptideMap, boost::unordered_map< String, String > &DecoySequenceMap, IonMapT &DecoyIonMap, PeptideMapT &DecoyPeptideMap)
	Generate decoy in silico map. More...

void	generateTargetAssays_ (const OpenMS::TargetedExperiment &exp, TransitionVectorType &transitions, double mz_threshold, const std::vector< std::pair< double, double > > &swathes, int round_decPow, const PeptideMapT &TargetPeptideMap, const IonMapT &TargetIonMap)
	Generate target identification transitions. More...

void	generateDecoyAssays_ (const OpenMS::TargetedExperiment &exp, TransitionVectorType &transitions, double mz_threshold, const std::vector< std::pair< double, double > > &swathes, int round_decPow, const PeptideMapT &DecoyPeptideMap, TargetDecoyMapT &TargetDecoyMap, const IonMapT &DecoyIonMap, const IonMapT &TargetIonMap)
	Generate decoy assays. More...

Additional Inherited Members
Static Protected Member Functions inherited from ProgressLogger
static String	logTypeToFactoryName_ (LogType type)
	Return the name of the factory product used for this log type. More...

Protected Attributes inherited from ProgressLogger
LogType	type_

time_t	last_invoke_

ProgressLoggerImpl *	current_logger_

Static Protected Attributes inherited from ProgressLogger
static int	recursion_depth_

Detailed Description

Generate assays from a TargetedExperiment.

Will generate assays from a raw, unfiltered TargetedExperiment, as can be generated by TargetedFileConverter.

Transitions can be selected according to a set of rules, as described in Schubert et al., 2015 (PMID 25675208).

In addition, unique ion signature (UIS) (Sherman et al., 2009; PMID 19556279) transitions can be generated based on empirically observed or in silico generated ion series. This is described in detail in the IPF paper (Rosenberger et al. 2017; PMID 28604659).

Member Typedef Documentation

◆ CompoundTransitionMapType

typedef std::map<String, std::vector<const ReactionMonitoringTransition*> > CompoundTransitionMapType

◆ CompoundVectorType

typedef std::vector<OpenMS::TargetedExperiment::Compound> CompoundVectorType

◆ FragmentSeqMap

typedef std::vector<std::pair<double, std::string> > FragmentSeqMap

Describes a fragment sequence map of : "fragment m/z" -> "modified sequence".

◆ IonMapT

typedef boost::unordered_map<size_t, boost::unordered_map<String, FragmentSeqMap > > IonMapT

Stores a mapping : "unmodified sequence" -> FragmentSeqMap for all SWATH windows.

◆ IonSeries

typedef std::vector<std::pair<std::string, double> > IonSeries

Describes an ion series: "ion_type" -> "fragment m/z".

◆ ModifiedSequenceMap

typedef boost::unordered_map<String, std::set<std::string> > ModifiedSequenceMap

Maps an unmodified sequence to all its modified sequences.

◆ PeptideMapT

typedef std::map<String, IonSeries > PeptideMapT

Maps a peptide sequence to an ion series: "ion_type" -> "fragment m/z".

◆ PeptideTransitionMapType

typedef std::map<String, std::vector<const ReactionMonitoringTransition*> > PeptideTransitionMapType

◆ PeptideVectorType

typedef std::vector<OpenMS::TargetedExperiment::Peptide> PeptideVectorType

◆ ProteinVectorType

typedef std::vector<OpenMS::TargetedExperiment::Protein> ProteinVectorType

◆ SequenceMapT

typedef boost::unordered_map<size_t, ModifiedSequenceMap> SequenceMapT

Stores the ModifiedSequenceMap for all SWATH windows.

◆ TargetDecoyMapT

typedef boost::unordered_map<String, TargetedExperiment::Peptide> TargetDecoyMapT

Maps the peptide id (same for target and decoy) to the decoy peptide object.

◆ TransitionVectorType

typedef std::vector<OpenMS::ReactionMonitoringTransition> TransitionVectorType

Constructor & Destructor Documentation

◆ MRMAssay()

MRMAssay ( )

Constructor.

◆ ~MRMAssay()

~MRMAssay ( )

Destructor.

Member Function Documentation

◆ addModificationsSequences_()

std::vector<OpenMS::AASequence> addModificationsSequences_	(	const std::vector< OpenMS::AASequence > &	sequences,
		const std::vector< std::vector< size_t > > &	mods_combs,
		const OpenMS::String &	modification
	)

protected

Generate modified peptide forms based on all possible combinations.

Parameters

sequences	template AASequences
mods_combs	all possible combinations (e.g. from nchoosekcombinations() )
modification	String of the modification

Returns: a vector of all modified peptides.

◆ detectingTransitions()

void detectingTransitions	(	OpenMS::TargetedExperiment &	exp,
		int	min_transitions,
		int	max_transitions
	)

Select detecting fragment ions.

Parameters

exp	the input, unfiltered transitions
min_transitions	the minimum number of transitions required per assay
max_transitions	the maximum number of transitions required per assay

◆ detectingTransitionsCompound()

void detectingTransitionsCompound	(	OpenMS::TargetedExperiment &	exp,
		int	min_transitions,
		int	max_transitions
	)

Filters transitions by intensity, only keeping the top N transitions.

Parameters

exp	the transition list which will be filtered
min_transitions	the minimum number of transitions required per assay
max_transitions	the maximum number of transitions required per assay

◆ generateDecoyAssays_()

void generateDecoyAssays_	(	const OpenMS::TargetedExperiment &	exp,
		TransitionVectorType &	transitions,
		double	mz_threshold,
		const std::vector< std::pair< double, double > > &	swathes,
		int	round_decPow,
		const PeptideMapT &	DecoyPeptideMap,
		TargetDecoyMapT &	TargetDecoyMap,
		const IonMapT &	DecoyIonMap,
		const IonMapT &	TargetIonMap
	)

protected

Generate decoy assays.

Used internally by the IPF algorithm, see MRMAssay::uisTransitions()

◆ generateDecoyInSilicoMap_()

void generateDecoyInSilicoMap_	(	const OpenMS::TargetedExperiment &	exp,
		const std::vector< String > &	fragment_types,
		const std::vector< size_t > &	fragment_charges,
		bool	enable_specific_losses,
		bool	enable_unspecific_losses,
		bool	enable_ms2_precursors,
		const std::vector< std::pair< double, double > > &	swathes,
		int	round_decPow,
		TargetDecoyMapT &	TargetDecoyMap,
		PeptideMapT &	TargetPeptideMap,
		boost::unordered_map< String, String > &	DecoySequenceMap,
		IonMapT &	DecoyIonMap,
		PeptideMapT &	DecoyPeptideMap
	)

protected

Generate decoy in silico map.

For each decoy peptide sequence, compute all alternative peptidoforms using all modification-carrying residue permutations (n choose k possibilities) that are physicochemically possible according to ModificationsDB.

Used internally by the IPF algorithm, see MRMAssay::uisTransitions()

◆ generateDecoySequences_()

void generateDecoySequences_	(	const SequenceMapT &	TargetSequenceMap,
		boost::unordered_map< String, String > &	DecoySequenceMap,
		int	shuffle_seed
	)

protected

Generate decoy sequences.

Generate decoy sequences for IPF algorithm which share peptidoform properties with targets.

Used internally by the IPF algorithm, see MRMAssay::uisTransitions()

◆ generateTargetAssays_()

void generateTargetAssays_	(	const OpenMS::TargetedExperiment &	exp,
		TransitionVectorType &	transitions,
		double	mz_threshold,
		const std::vector< std::pair< double, double > > &	swathes,
		int	round_decPow,
		const PeptideMapT &	TargetPeptideMap,
		const IonMapT &	TargetIonMap
	)

protected

Generate target identification transitions.

This function iterates over each (theoretical) transition of each target peptide and records the identity of all peptidoforms that map to each transition. The resulting transitions are stored in transitions.

Parameters

exp	The input experiment with the target peptides
transitions	The output containing annotated transitions with potential interferences
mz_threshold	The threshold for annotating transitions as equal
swathes	The swath windows used
round_decPow	round product m/z values to decimal power (default: -4)
TargetPeptideMap	Theoretical transitions for each peptide generated before
TargetIonMap	Theoretical transitions for each peptide generated before

Used internally by the IPF algorithm, see MRMAssay::uisTransitions()

◆ generateTargetInSilicoMap_()

void generateTargetInSilicoMap_	(	const OpenMS::TargetedExperiment &	exp,
		const std::vector< String > &	fragment_types,
		const std::vector< size_t > &	fragment_charges,
		bool	enable_specific_losses,
		bool	enable_unspecific_losses,
		bool	enable_ms2_precursors,
		const std::vector< std::pair< double, double > > &	swathes,
		int	round_decPow,
		size_t	max_num_alternative_localizations,
		SequenceMapT &	TargetSequenceMap,
		IonMapT &	TargetIonMap,
		PeptideMapT &	TargetPeptideMap
	)

protected

Generate target in silico map.

For each peptide, compute all alternative peptidoforms using all modification-carrying residue permutations (n choose k possibilities) that are physicochemically possible according to ModificationsDB.

Then store the ion series for each of these theoretical fragment ions in the provided maps TargetSequenceMap, TargetIonMap, TargetPeptideMap.

Used internally by the IPF algorithm, see MRMAssay::uisTransitions()

◆ generateTheoreticalPeptidoforms_()

std::vector<OpenMS::AASequence> generateTheoreticalPeptidoforms_ ( const OpenMS::AASequence & sequence )

protected

Generate alternative modified peptide forms according to ModificationsDB.

An input peptide sequence containing modifications is used as template to generate all modification-carrying residue permutations (n choose k possibilities) that are physicochemically possible according to ModificationsDB.

Parameters

sequence template AASequence

Returns: a vector of all alternative modified peptides.

◆ generateTheoreticalPeptidoformsDecoy_()

std::vector<OpenMS::AASequence> generateTheoreticalPeptidoformsDecoy_	(	const OpenMS::AASequence &	sequence,
		const OpenMS::AASequence &	decoy_sequence
	)

protected

Generate alternative modified peptide forms according to ModificationsDB.

An input peptide sequence containing modifications is used as template to generate all modification-carrying residue permutations (n choose k possibilities) that are physicochemically possible according to ModificationsDB. Instead of the target sequence, the permutations are transferred to the decoy sequence that might contain additional modifiable residues. E.g. target sequence SAS(Phospho)K could result in [SAS(Phospho)K, S(Phospho)ASK] but the responding set of the decoy sequence SSS(Phospho)K would be [SSS(Phospho)K, S(Phospho)SSK].

Parameters

sequence	template AASequence
decoy_sequence	template decoy AASequence

Returns: a vector of all alternative modified peptides.

◆ getMatchingPeptidoforms_()

std::vector<std::string> getMatchingPeptidoforms_	(	const double	fragment_ion,
		const FragmentSeqMap &	ions,
		const double	mz_threshold
	)

protected

Check whether fragment ion are unique ion signatures in vector within threshold and return matching peptidoforms.

Parameters

fragment_ion	the queried fragment ion
ions	a vector of pairs of fragment ion m/z and peptide sequences which could interfere with fragment_ion
mz_threshold	the threshold within which to search for interferences

Returns: a vector of strings containing all peptidoforms with which fragment_ion overlaps

◆ getRandomSequence_()

std::string getRandomSequence_	(	size_t	sequence_size,
		boost::variate_generator< boost::mt19937 &, boost::uniform_int<> >	pseudoRNG
	)

protected

Generates random peptide sequence.

Parameters

sequence_size	length of peptide sequence
pseudoRNG	a Boost pseudo RNG

Returns: random peptide sequence

◆ getSwath_()

int getSwath_	(	const std::vector< std::pair< double, double > > &	swathes,
		const double	precursor_mz
	)

protected

Get swath index (precursor isolation window ordinal) for a particular precursor.

Parameters

swathes	the swath window settings
precursor_mz	the query precursor m/z

Returns: index of swath where precursor_mz falls into

◆ isInSwath_()

bool isInSwath_	(	const std::vector< std::pair< double, double > > &	swathes,
		const double	precursor_mz,
		const double	product_mz
	)

protected

Check whether the product m/z of a transition falls into the precursor isolation window.

Parameters

swathes	the swath window settings
precursor_mz	the query precursor m/z
product_mz	the query product m/z

Returns: whether product m/z falls into precursor isolation window

◆ nchoosekcombinations_()

std::vector<std::vector<size_t> > nchoosekcombinations_	(	const std::vector< size_t > &	n,
		size_t	k
	)

protected

Computes all N choose K combinations.

Parameters

n	vector of N indices
k	number of K

Returns: a vector of all N index combinations

◆ reannotateTransitions()

void reannotateTransitions	(	OpenMS::TargetedExperiment &	exp,
		double	precursor_mz_threshold,
		double	product_mz_threshold,
		const std::vector< String > &	fragment_types,
		const std::vector< size_t > &	fragment_charges,
		bool	enable_specific_losses,
		bool	enable_unspecific_losses,
		int	round_decPow = `-4`
	)

Annotates and filters transitions in a TargetedExperiment.

Parameters

exp	the input, unfiltered transitions
precursor_mz_threshold	the precursor m/z threshold in Th for annotation
product_mz_threshold	the product m/z threshold in Th for annotation
fragment_types	the fragment types to consider for annotation
fragment_charges	the fragment charges to consider for annotation
enable_specific_losses	whether specific neutral losses should be considered
enable_unspecific_losses	whether unspecific neutral losses (H2O1, H3N1, C1H2N2, C1H2N1O1) should be considered
round_decPow	round product m/z values to decimal power (default: -4)

◆ restrictTransitions()

void restrictTransitions	(	OpenMS::TargetedExperiment &	exp,
		double	lower_mz_limit,
		double	upper_mz_limit,
		const std::vector< std::pair< double, double > > &	swathes
	)

Restrict and filter transitions in a TargetedExperiment.

Parameters

exp	the input, unfiltered transitions
lower_mz_limit	the lower product m/z limit in Th
upper_mz_limit	the upper product m/z limit in Th
swathes	the swath window settings (to exclude fragment ions falling into the precursor isolation window)

◆ uisTransitions()

void uisTransitions	(	OpenMS::TargetedExperiment &	exp,
		const std::vector< String > &	fragment_types,
		const std::vector< size_t > &	fragment_charges,
		bool	enable_specific_losses,
		bool	enable_unspecific_losses,
		bool	enable_ms2_precursors,
		double	mz_threshold,
		const std::vector< std::pair< double, double > > &	swathes,
		int	round_decPow = `-4`,
		size_t	max_num_alternative_localizations = `20`,
		int	shuffle_seed = `-1`,
		bool	disable_decoy_transitions = `false`
	)

Annotate UIS / site-specific transitions.

Performs the following actions:

Step 1: For each peptide, compute all theoretical alternative peptidoforms; see transitions generateTargetInSilicoMap_()
Step 2: Generate target identification transitions; see generateTargetAssays_()
Step 3a: Generate decoy sequences that share peptidoform properties with targets; see generateDecoySequences_()
Step 3b: Generate decoy in silico peptide map containing theoretical transition; see generateDecoyInSilicoMap_()
Step 4: Generate decoy identification transitions; see generateDecoyAssays_()

The IPF algorithm uses the concept of "identification transitions" that are used to discriminate different peptidoforms, these are generated in this function. In brief, the algorithm takes the existing set of peptides and transitions and then appends these "identification transitions" for targets and decoys. The novel transitions are set to be non-detecting and non-quantifying and are annotated with the set of peptidoforms to which they map.

Parameters

exp	the input, unfiltered transitions
fragment_types	the fragment types to consider for annotation
fragment_charges	the fragment charges to consider for annotation
enable_specific_losses	whether specific neutral losses should be considered
enable_unspecific_losses	whether unspecific neutral losses (H2O1, H3N1, C1H2N2, C1H2N1O1) should be considered
enable_ms2_precursors	whether MS2 precursors should be considered
mz_threshold	the product m/z threshold in Th for annotation
swathes	the swath window settings (to exclude fragment ions falling
round_decPow	round product m/z values to decimal power (default: -4)
max_num_alternative_localizations	maximum number of allowed peptide sequence permutations
shuffle_seed	set seed for shuffle (-1: select seed based on time)
disable_decoy_transitions	whether to disable generation of decoy UIS transitions

Public Types

Public Member Functions

Protected Member Functions

Additional Inherited Members

Detailed Description

Member Typedef Documentation

◆ CompoundTransitionMapType

◆ CompoundVectorType

◆ FragmentSeqMap

◆ IonMapT

◆ IonSeries

◆ ModifiedSequenceMap

◆ PeptideMapT

◆ PeptideTransitionMapType

◆ PeptideVectorType

◆ ProteinVectorType

◆ SequenceMapT

◆ TargetDecoyMapT

◆ TransitionVectorType

Constructor & Destructor Documentation

◆ MRMAssay()

◆ ~MRMAssay()

Member Function Documentation

◆ addModificationsSequences_()

◆ detectingTransitions()

◆ detectingTransitionsCompound()

◆ generateDecoyAssays_()

◆ generateDecoyInSilicoMap_()

◆ generateDecoySequences_()

◆ generateTargetAssays_()

◆ generateTargetInSilicoMap_()

◆ generateTheoreticalPeptidoforms_()

◆ generateTheoreticalPeptidoformsDecoy_()

◆ getMatchingPeptidoforms_()

◆ getRandomSequence_()

◆ getSwath_()

◆ isInSwath_()

◆ nchoosekcombinations_()

◆ reannotateTransitions()

◆ restrictTransitions()

◆ uisTransitions()