Completes peptide multiplets and resolves quant/ID conflicts within them. More...

#include <OpenMS/FEATUREFINDER/MultiplexResolverAlgorithm.h>

Inheritance diagram for MultiplexResolverAlgorithm:

Public Member Functions
	MultiplexResolverAlgorithm ()
	Constructor; registers the `algorithm` and `labels` parameter sections.

void	resolve (const ConsensusMap &map_in, ConsensusMap &map_out, ConsensusMap &map_conflicts, const MSExperiment &blacklist=MSExperiment()) const
	Split the annotated multiplets of `map_in` into resolved and conflicting ones.

std::vector< bool >	checkIdentifications (const ConsensusFeature &consensus) const
	Which peptide identifications of `consensus` agree with its detected mass shifts?

std::vector< double >	expectedChannelMZs (const AASequence &sequence, int charge, Size &position) const
	Where the peptide of `sequence` appears in every channel.

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

	DefaultParamHandler (const DefaultParamHandler &rhs)
	Copy constructor.

virtual	~DefaultParamHandler ()
	Destructor.

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

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

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

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

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

const std::string &	getName () const
	Non-mutable access to the name.

void	setName (const std::string &name)
	Mutable access to the name.

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

Protected Member Functions
MultiplexDeltaMassesGenerator	createGenerator_ () const
	The generator of the theoretical mass-shift patterns, as configured in the sections `algorithm` and `labels`.

bool	matchDeltaMasses_ (const ConsensusFeature &consensus, double detected_delta_mass_at_label_set, const std::vector< MultiplexDeltaMasses::DeltaMass > &pattern, double theoretical_delta_mass_at_label_set, std::vector< bool > &delta_mass_matched) const
	Check whether all delta masses of the detected pattern match one of the theoretical pattern.

int	findMatchingPattern_ (const ConsensusFeature &consensus, double detected_delta_mass_at_label_set, const AASequence &sequence, const MultiplexDeltaMasses::LabelSet &label_set, const std::vector< MultiplexDeltaMasses > &theoretical_patterns, std::vector< bool > &delta_mass_matched, int &index_label_set) const
	Find the theoretical delta mass pattern matching the detected one.

bool	isBlacklisted_ (const MSExperiment &blacklist, double rt, double mz, size_t charge, const ConsensusFeature &consensus) const
	Is one of the first three isotopes of a (dummy) feature at this position blacklisted?

ConsensusFeature	completeConsensus_ (const ConsensusFeature &consensus, const std::vector< MultiplexDeltaMasses::DeltaMass > &pattern, const std::vector< bool > &delta_mass_matched, int index_label_set, const MSExperiment &blacklist) const
	Complete an incomplete multiplet with dummy features.

void	updateMembers_ () override
	This method is used to update extra member variables at the end of the setParameters() method.

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

Static Protected Member Functions
static double	deltaMassFromMapIndex_ (const ConsensusFeature::HandleSetType &feature_handles, unsigned idx)
	Relative delta mass between the first feature handle and the handle with map index `idx` (NaN if absent)

static double	matchLabelSet_ (const std::vector< MultiplexDeltaMasses::DeltaMass > &pattern, const MultiplexDeltaMasses::LabelSet &label_set, int &index_label_set)
	Mass shift of the theoretical pattern whose label set equals `label_set`.

static bool	matchesResidues_ (const std::vector< MultiplexDeltaMasses::DeltaMass > &pattern, const AASequence &sequence)
	Does every channel of `pattern` label as many residues as `sequence` has?

static double	findNewMZ_ (double mz, int charge, const std::vector< MultiplexDeltaMasses::DeltaMass > &pattern, const std::vector< bool > &delta_mass_matched)
	m/z of the lightest peptide of the complete multiplet, given the incomplete one at `mz`

Protected Attributes
double	mass_tolerance_ = 0.1
	Mass tolerance in Da for matching detected to theoretical mass shifts.

double	mz_tolerance_ = 10.0
	m/z tolerance in ppm for the blacklist check

double	rt_tolerance_ = 5.0
	RT tolerance in seconds for the blacklist check.

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

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

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

std::string	error_name_
	Name that is displayed in error messages during the parameter checking.

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

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

Additional Inherited Members
Static Public Member Functions inherited from DefaultParamHandler
static void	writeParametersToMetaValues (const Param &write_this, MetaInfoInterface &write_here, const std::string &key_prefix="")
	Writes all parameters to meta values.

Detailed Description

Completes peptide multiplets and resolves quant/ID conflicts within them.

Tools such as FeatureFinderMultiplexAlgorithm detect peptide feature multiplets (pairs, triplets, ...) in MS1-labeled data (SILAC, Dimethyl, ...). Once the multiplets carry peptide sequences (e.g. via IDMapper), this class consolidates quantitative and sequence information in two steps:

Multiplets whose observed mass shifts contradict the labels found in the annotated sequence are moved to a conflict map. Example: a sequence carrying a single Arg10 label mapped to the light feature of a SILAC triplet - either the feature detection or the sequence is wrong.
Incomplete multiplets (e.g. only the heavy partner of a pair was detected) are completed with dummy features. A dummy feature gets intensity 0 when nothing was blacklisted around its position during feature detection (the peptide is absent), and NaN (not quantifiable) when the region was blacklisted, i.e. another feature overlaps with it.

Only the first peptide identification of a consensus feature is taken into account, so the map should have been reduced to one identification per feature (IDConflictResolverAlgorithm::resolve()) first. checkIdentifications() tells beforehand which of several identifications agree with a multiplet, so that the reduction can prefer one of those over a better-scoring one that would make the multiplet a conflict. Multiplets without sequence annotation are written to the conflict map unchanged.

The identifications must carry the map index of the feature handle they were mapped to in the meta value map_index (IDMapper with annotate_ids_with_subelements). When a multiplet is completed, the new map index of the identified feature is recorded in the meta value map_index of the first peptide hit.

Parameters: section algorithm holds the label specification and tolerances, section labels the mass shift of every known label (see MultiplexDeltaMassesGenerator).

Parameters of this class are:

Name	Type	Default	Restrictions	Description
algorithm:labels	string	[][Lys8,Arg10]		Labels used for labelling the samples. [...] specifies the labels for a single sample. For example [][Lys8,Arg10] ... SILAC [][Lys4,Arg6][Lys8,Arg10] ... triple-SILAC [Dimethyl0][Dimethyl6] ... Dimethyl [Dimethyl0][Dimethyl4][Dimethyl8] ... triple Dimethyl [ICPL0][ICPL4][ICPL6][ICPL10] ... ICPL
algorithm:max_nr_labelled_aas	int	0	min: 0	Maximum number of labelled amino acids per peptide, minus one. The algorithm searches for peptides with up to (this value + 1) labelled amino acids. For SILAC with trypsin digestion, this parameter corresponds to the maximum number of missed cleavages.
algorithm:mass_tolerance	float	0.1		Mass tolerance in Da for matching the mass shifts in the detected peptide multiplet to the theoretical mass shift pattern.
algorithm:mz_tolerance	float	10.0	min: 0.0	m/z tolerance in ppm for checking if dummy feature vicinity was blacklisted.
algorithm:rt_tolerance	float	5.0	min: 0.0	Retention time tolerance in seconds for checking if dummy feature vicinity was blacklisted.
labels:Arg6	float	6.0201290268	min: 0.0	Label:13C(6) \| C(-6) 13C(6) \| unimod @#188
labels:Arg10	float	10.008268599999999	min: 0.0	Label:13C(6)15N(4) \| C(-6) 13C(6) N(-4) 15N(4) \| unimod @#267
labels:Lys4	float	4.0251069836	min: 0.0	Label:2H(4) \| H(-4) 2H(4) \| unimod @#481
labels:Lys6	float	6.0201290268	min: 0.0	Label:13C(6) \| C(-6) 13C(6) \| unimod @#188
labels:Lys8	float	8.0141988132	min: 0.0	Label:13C(6)15N(2) \| C(-6) 13C(6) N(-2) 15N(2) \| unimod @#259
labels:Leu3	float	3.01883	min: 0.0	Label:2H(3) \| H(-3) 2H(3) \| unimod @#262
labels:Dimethyl0	float	28.031300000000002	min: 0.0	Dimethyl \| H(4) C(2) \| unimod @#36
labels:Dimethyl4	float	32.056407	min: 0.0	Dimethyl:2H(4) \| 2H(4) C(2) \| unimod @#199
labels:Dimethyl6	float	34.063116999999998	min: 0.0	Dimethyl:2H(4)13C(2) \| 2H(4) 13C(2) \| unimod @#510
labels:Dimethyl8	float	36.075670000000002	min: 0.0	Dimethyl:2H(6)13C(2) \| H(-2) 2H(6) 13C(2) \| unimod @#330
labels:ICPL0	float	105.021463999999995	min: 0.0	ICPL \| H(3) C(6) N O \| unimod @#365
labels:ICPL4	float	109.046571	min: 0.0	ICPL:2H(4) \| H(-1) 2H(4) C(6) N O \| unimod @#687
labels:ICPL6	float	111.041593000000006	min: 0.0	ICPL:13C(6) \| H(3) 13C(6) N O \| unimod @#364
labels:ICPL10	float	115.066699999999997	min: 0.0	ICPL:13C(6)2H(4) \| H(-1) 2H(4) 13C(6) N O \| unimod @#866

Note:

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

Constructor & Destructor Documentation

◆ MultiplexResolverAlgorithm()

MultiplexResolverAlgorithm ( )

Constructor; registers the algorithm and labels parameter sections.

Member Function Documentation

◆ checkIdentifications()

std::vector< bool > checkIdentifications ( const ConsensusFeature & consensus ) const

Which peptide identifications of consensus agree with its detected mass shifts?

This is the check resolve() applies to the (first) identification of a multiplet, for every identification: the label set of its first peptide hit has to occur in a theoretical pattern whose mass shifts explain every detected feature, relative to the feature named by the identification's map_index. Use it to choose, among several identifications mapped onto one multiplet, one that does not turn the multiplet into a conflict.

Returns: One flag per peptide identification of consensus, in order. Identifications without hits, without map_index, or whose map_index names no feature handle are not consistent.

◆ completeConsensus_()

ConsensusFeature completeConsensus_	(	const ConsensusFeature &	consensus,
		const std::vector< MultiplexDeltaMasses::DeltaMass > &	pattern,
		const std::vector< bool > &	delta_mass_matched,
		int	index_label_set,
		const MSExperiment &	blacklist
	)		const

protected

Complete an incomplete multiplet with dummy features.

Parameters

[in]	consensus	Possibly incomplete multiplet
[in]	pattern	Matching theoretical pattern
[in]	delta_mass_matched	Which delta masses of the pattern were matched
[in]	index_label_set	Index within the pattern at which the label set was matched
[in]	blacklist	Blacklisted spectral peaks (may be empty)

Returns: The complete multiplet

◆ createGenerator_()

MultiplexDeltaMassesGenerator createGenerator_ ( ) const

protected

The generator of the theoretical mass-shift patterns, as configured in the sections algorithm and labels.

◆ deltaMassFromMapIndex_()

static double deltaMassFromMapIndex_	(	const ConsensusFeature::HandleSetType &	feature_handles,
		unsigned	idx
	)

staticprotected

Relative delta mass between the first feature handle and the handle with map index idx (NaN if absent)

◆ expectedChannelMZs()

std::vector< double > expectedChannelMZs	(	const AASequence &	sequence,
		int	charge,
		Size &	position
	)		const

Where the peptide of sequence appears in every channel.

The theoretical pattern of the peptide is the one whose label set at some position equals the labels of sequence and whose channels label as many residues as it has (see matchesResidues_()). Its mass shifts, relative to the position of sequence, give the m/z of the peptide at charge charge in every channel.

Parameters

[in]	sequence	Identified peptidoform, with its labels
[in]	charge	Charge state (non-zero)
[out]	position	Position (channel) of `sequence` itself within the returned m/z values

Returns: The m/z per channel (pattern position), empty if no theoretical pattern fits sequence

◆ findMatchingPattern_()

int findMatchingPattern_	(	const ConsensusFeature &	consensus,
		double	detected_delta_mass_at_label_set,
		const AASequence &	sequence,
		const MultiplexDeltaMasses::LabelSet &	label_set,
		const std::vector< MultiplexDeltaMasses > &	theoretical_patterns,
		std::vector< bool > &	delta_mass_matched,
		int &	index_label_set
	)		const

protected

Find the theoretical delta mass pattern matching the detected one.

Parameters

[in]	consensus	Detected pattern
[in]	detected_delta_mass_at_label_set	Detected mass shift of the identified feature (relative to the first feature)
[in]	sequence	Sequence annotated to the detected pattern
[in]	label_set	Label set extracted from `sequence`
[in]	theoretical_patterns	All theoretical patterns
[out]	delta_mass_matched	Which delta masses of the matching pattern were matched
[out]	index_label_set	Index within the matching pattern at which the label set was matched

Returns: Index of the matching pattern, or -1

◆ findNewMZ_()

static double findNewMZ_	(	double	mz,
		int	charge,
		const std::vector< MultiplexDeltaMasses::DeltaMass > &	pattern,
		const std::vector< bool > &	delta_mass_matched
	)

staticprotected

m/z of the lightest peptide of the complete multiplet, given the incomplete one at mz

◆ isBlacklisted_()

bool isBlacklisted_	(	const MSExperiment &	blacklist,
		double	rt,
		double	mz,
		size_t	charge,
		const ConsensusFeature &	consensus
	)		const

protected

Is one of the first three isotopes of a (dummy) feature at this position blacklisted?

◆ matchDeltaMasses_()

bool matchDeltaMasses_	(	const ConsensusFeature &	consensus,
		double	detected_delta_mass_at_label_set,
		const std::vector< MultiplexDeltaMasses::DeltaMass > &	pattern,
		double	theoretical_delta_mass_at_label_set,
		std::vector< bool > &	delta_mass_matched
	)		const

protected

Check whether all delta masses of the detected pattern match one of the theoretical pattern.

Parameters

[in]	consensus	Detected pattern
[in]	detected_delta_mass_at_label_set	Detected mass shift of the identified feature (relative to the first feature)
[in]	pattern	Theoretical pattern
[in]	theoretical_delta_mass_at_label_set	Theoretical mass shift at which the label set was matched
[out]	delta_mass_matched	Which delta masses of the theoretical pattern were matched

Returns: true if every detected delta mass has a theoretical counterpart within the mass tolerance

◆ matchesResidues_()

static bool matchesResidues_	(	const std::vector< MultiplexDeltaMasses::DeltaMass > &	pattern,
		const AASequence &	sequence
	)

staticprotected

Does every channel of pattern label as many residues as sequence has?

Metabolic labels (SILAC Lys/Arg, Leu3) sit on every residue of their kind, so in a pattern that fits the peptide, each channel carries one Lys label per K, one Arg label per R and one Leu label per L - counted for the residue kinds the channel labels at all. This tells the pattern of an unlabelled identification, whose label set ("no_label") occurs in every pattern, e.g. a light singlet of a K-terminal peptide must not be completed with Arg-shifted channels. Other labels (Dimethyl, ICPL, plain mass shifts) are not counted.

◆ matchLabelSet_()

static double matchLabelSet_	(	const std::vector< MultiplexDeltaMasses::DeltaMass > &	pattern,
		const MultiplexDeltaMasses::LabelSet &	label_set,
		int &	index_label_set
	)

staticprotected

Mass shift of the theoretical pattern whose label set equals label_set.

Parameters

[in]	pattern	Theoretical pattern
[in]	label_set	Label set of the detected pattern
[out]	index_label_set	Index within the pattern at which the label set was matched

Returns: Mass shift at the match, or NaN if no delta mass carries this label set

◆ resolve()

void resolve	(	const ConsensusMap &	map_in,
		ConsensusMap &	map_out,
		ConsensusMap &	map_conflicts,
		const MSExperiment &	blacklist = `MSExperiment()`
	)		const

Split the annotated multiplets of map_in into resolved and conflicting ones.

map_out and map_conflicts inherit the meta data of map_in (column headers, protein identifications, unassigned peptide identifications, data processing) and receive the consensus features that could resp. could not be matched to a theoretical mass-shift pattern. Both output maps get fresh unique ids for their features, and the column header sizes of map_out are set to its number of features.

Parameters

[in]	map_in	Multiplets with (at most one) peptide identification each
[out]	map_out	Complete, consistent multiplets; cleared first
[out]	map_conflicts	Multiplets without identification or with conflicting quant/ID information; cleared first
[in]	blacklist	Spectral peaks blacklisted during feature detection (FeatureFinderMultiplexAlgorithm::getBlacklist()). Used to decide whether a dummy feature is absent (intensity 0) or not quantifiable (NaN). May be empty.

Exceptions

Exception::MissingInformation	if an identified feature lacks the `map_index` meta value
Exception::InvalidValue	if the `map_index` does not name a feature handle of the consensus feature

◆ updateMembers_()

void updateMembers_ ( )

overrideprotectedvirtual

This method is used to update extra member variables at the end of the setParameters() method.

Also call it at the end of the derived classes' copy constructor and assignment operator.

The default implementation is empty.

Reimplemented from DefaultParamHandler.

Member Data Documentation

◆ mass_tolerance_

double mass_tolerance_ = 0.1

protected

Mass tolerance in Da for matching detected to theoretical mass shifts.

◆ mz_tolerance_

double mz_tolerance_ = 10.0

protected

m/z tolerance in ppm for the blacklist check

◆ rt_tolerance_

double rt_tolerance_ = 5.0

protected

RT tolerance in seconds for the blacklist check.

Public Member Functions

Protected Member Functions

Static Protected Member Functions

Protected Attributes

Additional Inherited Members

Detailed Description

Constructor & Destructor Documentation

◆ MultiplexResolverAlgorithm()

Member Function Documentation

◆ checkIdentifications()

◆ completeConsensus_()

◆ createGenerator_()

◆ deltaMassFromMapIndex_()

◆ expectedChannelMZs()

◆ findMatchingPattern_()

◆ findNewMZ_()

◆ isBlacklisted_()

◆ matchDeltaMasses_()

◆ matchesResidues_()

◆ matchLabelSet_()

◆ resolve()

◆ updateMembers_()

Member Data Documentation

◆ mass_tolerance_

◆ mz_tolerance_

◆ rt_tolerance_