Localizes a cross-link by the chemistry of the cross-linker, within the residues the fragment ions support. More...

#include <OpenNuXL/include/NuXLSiteLocalization.h>

Classes
struct	ProteinTermini
	Protein N- and C-terminal peptides of a digest, sorted, to look them up with isProteinNTerminal and isProteinCTerminal. More...

struct	Site
	Result of localizing one cross-link. More...

Static Public Member Functions
static std::vector< int >	supportedResidues (const std::vector< double > &n_shifts, const std::vector< double > &n_noshifts, const std::vector< double > &c_shifts, const std::vector< double > &c_noshifts, double tolerance=DEFAULT_TOLERANCE)
	Residues at which a cross-link explains the fragment ions best.

static Site	localizeNHS (const std::string &sequence, bool reactive_protein_n_term, const std::vector< double > &n_shifts, const std::vector< double > &n_noshifts, const std::vector< double > &c_shifts, const std::vector< double > &c_noshifts, double tolerance=DEFAULT_TOLERANCE, const std::vector< bool > &blocked={})
	Localizes a cross-link attached through an NHS ester.

static void	digestProtein (const EnzymaticDigestion &digestion, std::string_view protein, size_t min_length, size_t max_length, bool clip_nterm_methionine, std::vector< std::string_view > &peptides)
	The peptides of a protein as searched: its digest and, optionally, its N-terminal peptides after removal of the initial methionine.

static ProteinTermini	proteinTermini (const std::vector< std::string_view > &proteins, const EnzymaticDigestion &digestion, size_t min_length, size_t max_length, bool clip_nterm_methionine)
	The protein-terminal peptides among the peptides digestProtein yields for `proteins`.

static bool	isProteinNTerminal (const ProteinTermini &termini, std::string_view peptide)
	Whether `peptide` is a protein N-terminal digestion product (see proteinTermini)

static bool	isProteinCTerminal (const ProteinTermini &termini, std::string_view peptide)
	Whether `peptide` is a protein C-terminal digestion product (see proteinTermini)

Static Public Attributes
static constexpr double	DEFAULT_TOLERANCE = 0.1
	Default fraction of the fragment intensity by which a residue's support may fall short of the best and still count as supported.

Detailed Description

Localizes a cross-link by the chemistry of the cross-linker, within the residues the fragment ions support.

Used for cross-linkers that bind the protein through an NHS ester (e.g. SDA): these react with the protein N-terminus and lysines, and much less with serine, threonine and tyrosine (mainly next to a histidine, see Mädler et al., J. Mass Spectrom. 2009, 44, 694-706).

Localization works in two steps:

supportedResidues determines the residues the fragment ions can't tell apart (the ambiguity stretch, like the lower-case range in the MSFragger localization).
localizeNHS picks the site in that stretch by the NHS chemistry.

The fragment evidence is passed per residue, as summed intensities of the a/b- and y-ions: index i of n_shifts / n_noshifts is the prefix ion that ends at residue i (b_i+1), index i of c_shifts / c_noshifts is the suffix ion that starts at residue i (y_length-i). "shifts" are ions carrying a cross-linker fragment adduct, "noshifts" ions without. All residue positions are 0-based.

Class Documentation

◆ OpenMS::NuXLSiteLocalization::ProteinTermini

struct OpenMS::NuXLSiteLocalization::ProteinTermini

Protein N- and C-terminal peptides of a digest, sorted, to look them up with isProteinNTerminal and isProteinCTerminal.

Class Members
vector< string >	c_terminal	peptides that end a protein
vector< string >	n_terminal	peptides that start a protein (also right behind a clipped initial methionine)

◆ OpenMS::NuXLSiteLocalization::Site

struct OpenMS::NuXLSiteLocalization::Site

Result of localizing one cross-link.

Class Members
string	method = "unlocalized"	how the site was chosen: "N-term", "K", "STY+H" or "unlocalized"
int	position = -1	localized residue, -1 if unlocalized
int	range_begin = -1	first residue supported by the fragment ions, -1 without fragment evidence
int	range_end = -1	last residue supported by the fragment ions, -1 without fragment evidence

Member Function Documentation

◆ digestProtein()

void digestProtein	(	const EnzymaticDigestion &	digestion,
		std::string_view	protein,
		size_t	min_length,
		size_t	max_length,
		bool	clip_nterm_methionine,
		std::vector< std::string_view > &	peptides
	)

static

The peptides of a protein as searched: its digest and, optionally, its N-terminal peptides after removal of the initial methionine.

Parameters

[in]	digestion	the enzyme and missed cleavages of the search
[in]	protein	protein sequence
[in]	min_length	minimum peptide length
[in]	max_length	maximum peptide length (0: no limit)
[in]	clip_nterm_methionine	also the N-terminal products of the protein without its initial methionine, if it starts with M
[out]	peptides	views into `protein`

References EnzymaticDigestion::digestUnmodified().

Referenced by NuXLSiteLocalization::proteinTermini().

◆ isProteinCTerminal()

bool isProteinCTerminal	(	const ProteinTermini &	termini,
		std::string_view	peptide
	)

static

Whether peptide is a protein C-terminal digestion product (see proteinTermini)

References NuXLSiteLocalization::ProteinTermini::c_terminal.

Referenced by NuXLAnnotateAndLocate::annotateAndLocate_().

◆ isProteinNTerminal()

bool isProteinNTerminal	(	const ProteinTermini &	termini,
		std::string_view	peptide
	)

static

Whether peptide is a protein N-terminal digestion product (see proteinTermini)

References NuXLSiteLocalization::ProteinTermini::n_terminal.

Referenced by NuXLAnnotateAndLocate::annotateAndLocate_().

◆ localizeNHS()

NuXLSiteLocalization::Site localizeNHS	(	const std::string &	sequence,
		bool	reactive_protein_n_term,
		const std::vector< double > &	n_shifts,
		const std::vector< double > &	n_noshifts,
		const std::vector< double > &	c_shifts,
		const std::vector< double > &	c_noshifts,
		double	tolerance = `DEFAULT_TOLERANCE`,
		const std::vector< bool > &	blocked = `{}`
	)

static

Localizes a cross-link attached through an NHS ester.

Among the supportedResidues, in this order:

the peptide N-terminus, if reactive_protein_n_term (the peptide starts the protein and its N-terminus is free) and the first residue is supported;
the lysine closest to the middle of the supported residues;
the serine, threonine or tyrosine closest to the middle of the supported residues that has a histidine within four residues in the peptide;
otherwise the cross-link stays unlocalized.

Ties go to the residue closer to the N-terminus. Residues flagged in blocked are skipped.

Parameters

[in]	sequence	unmodified peptide sequence
[in]	reactive_protein_n_term	whether the peptide N-terminus is the free N-terminus of a protein
[in]	n_shifts	intensity of the shifted prefix (a/b) ions ending at each residue
[in]	n_noshifts	intensity of the unshifted prefix (a/b) ions ending at each residue
[in]	c_shifts	intensity of the shifted suffix (y) ions starting at each residue
[in]	c_noshifts	intensity of the unshifted suffix (y) ions starting at each residue
[in]	tolerance	see supportedResidues
[in]	blocked	per residue, whether a modification blocks its reactive group (e.g. an acetylated lysine); empty: none

References NuXLSiteLocalization::Site::method, NuXLSiteLocalization::Site::position, NuXLSiteLocalization::Site::range_begin, NuXLSiteLocalization::Site::range_end, and NuXLSiteLocalization::supportedResidues().

Referenced by NuXLAnnotateAndLocate::annotateAndLocate_().

◆ proteinTermini()

NuXLSiteLocalization::ProteinTermini proteinTermini	(	const std::vector< std::string_view > &	proteins,
		const EnzymaticDigestion &	digestion,
		size_t	min_length,
		size_t	max_length,
		bool	clip_nterm_methionine
	)

static

The protein-terminal peptides among the peptides digestProtein yields for proteins.

Only digestion products count: a peptide that merely is a prefix or suffix of a protein, without being produced from its terminus, is not protein-terminal.

References NuXLSiteLocalization::ProteinTermini::c_terminal, NuXLSiteLocalization::digestProtein(), and NuXLSiteLocalization::ProteinTermini::n_terminal.

◆ supportedResidues()

vector< int > supportedResidues	(	const std::vector< double > &	n_shifts,
		const std::vector< double > &	n_noshifts,
		const std::vector< double > &	c_shifts,
		const std::vector< double > &	c_noshifts,
		double	tolerance = `DEFAULT_TOLERANCE`
	)

static

Residues at which a cross-link explains the fragment ions best.

For every residue, sums the intensity of the ions consistent with a cross-link there (shifted ions that contain the residue, unshifted ions that don't) minus the intensity of the inconsistent ones. Returns the residues whose sum is at most tolerance times the total fragment intensity below the highest one, so that a single weak or misassigned ion doesn't decide. They are usually contiguous; contradicting ions can support residues on both sides of unsupported ones. Residues no ion separates get the same sum (e.g., the first two residues without a₁/b₁ and y_length-1 ions). Unshifted ions alone also limit the range. Unshifted a₁/b₁ ions are ignored: b₁ of lysine coincides with common lysine ions of any peptide.

Parameters

[in]	n_shifts	intensity of the shifted prefix (a/b) ions ending at each residue
[in]	n_noshifts	intensity of the unshifted prefix (a/b) ions ending at each residue
[in]	c_shifts	intensity of the shifted suffix (y) ions starting at each residue
[in]	c_noshifts	intensity of the unshifted suffix (y) ions starting at each residue
[in]	tolerance	fraction of the total fragment intensity by which a residue's sum may fall short of the highest

Returns: supported residues (0-based, ascending); empty without any fragment evidence

Referenced by NuXLSiteLocalization::localizeNHS().

Member Data Documentation

◆ DEFAULT_TOLERANCE

constexpr double DEFAULT_TOLERANCE = 0.1

staticconstexpr

Default fraction of the fragment intensity by which a residue's support may fall short of the best and still count as supported.

Referenced by NuXLAnnotateAndLocate::annotateAndLocate_().

Classes

Static Public Member Functions

Static Public Attributes

Detailed Description

Class Documentation

◆ OpenMS::NuXLSiteLocalization::ProteinTermini

◆ OpenMS::NuXLSiteLocalization::Site

Member Function Documentation

◆ digestProtein()

◆ isProteinCTerminal()

◆ isProteinNTerminal()

◆ localizeNHS()

◆ proteinTermini()

◆ supportedResidues()

Member Data Documentation

◆ DEFAULT_TOLERANCE