peptide
Version:
160 lines • 7.48 kB
JavaScript
;
Object.defineProperty(exports, "__esModule", { value: true });
exports.digestPeptide = digestPeptide;
const ml_spectra_processing_1 = require("ml-spectra-processing");
/**
* Digest a peptide sequence using a specified enzyme.
* @param {string} sequence - The peptide sequence to digest.
* @param {object} [options={}] - Digestion options.
* @param {string} options.enzyme - The enzyme to use for digestion. Required. Supported values: 'chymotrypsin', 'trypsin', 'lysc', 'glucph4', 'glucph8', 'thermolysin', 'cyanogenbromide', 'any'.
* @param {number} [options.minMissed=0] - Minimum number of missed cleavages.
* @param {number} [options.maxMissed=0] - Maximum number of missed cleavages.
* @param {number} [options.minResidue=0] - Minimum number of residues in a fragment.
* @param {number} [options.maxResidue=Infinity] - Maximum number of residues in a fragment.
* @param {number} [options.minDigestions=0] - Minimum number of cleavage sites to use. Generates all combinations with at least this many cleavages. Defaults to `0`.
* @param {number} [options.maxDigestions=Infinity] - Maximum number of cleavage sites to use. Generates all combinations with at most this many cleavages. Defaults to `Infinity`.
* @returns {string[]} Array of digested peptide fragments.
*/
function digestPeptide(sequence, options = {}) {
const { enzyme, minMissed = 0, maxMissed = 0, minResidue = 0, maxResidue = Number.MAX_VALUE, minDigestions = 0, maxDigestions = Number.MAX_VALUE, } = options;
if (!enzyme) {
return [];
}
sequence = sequence.replace(/^H([^a-z])/, '$1').replace(/OH$/, '');
let regexp = getRegexp(enzyme);
let allFragments = sequence.replace(regexp, '$1 ').split(/ /).filter(Boolean);
const numCleavages = allFragments.length - 1;
// Return empty if minDigestions is impossible to achieve
if (minDigestions > numCleavages) {
return [];
}
const effectiveMaxDigestions = Math.min(maxDigestions, numCleavages);
const effectiveMinDigestions = minDigestions;
if (effectiveMinDigestions > effectiveMaxDigestions) {
return [];
}
// Determine if we need combinatorial approach
// Use combinatorial logic when maxDigestions explicitly limits cleavages OR minDigestions > 0
const useCombinatorial = maxDigestions < numCleavages || minDigestions > 0;
// When using combinatorial due to maxDigestions limit, ensure at least 1 cleavage
const startDigestions = useCombinatorial
? Math.max(1, effectiveMinDigestions)
: effectiveMinDigestions;
if (!useCombinatorial) {
// Default behavior: use all available cleavage sites
const results = [];
const fragments = [];
let fragmentStart = 0;
for (let i = 0; i < allFragments.length; i++) {
let nbResidue = allFragments[i]
.replaceAll(/([A-Z][a-z]{2})/g, ' $1')
.split(/ /)
.filter(Boolean).length;
fragments.push({
sequence: allFragments[i],
nbResidue,
from: fragmentStart,
to: fragmentStart + nbResidue - 1,
});
fragmentStart += nbResidue;
}
for (let i = 0; i < fragments.length - minMissed; i++) {
for (let j = minMissed; j <= Math.min(maxMissed, fragments.length - i - 1); j++) {
let fragment = '';
let nbResidue = 0;
for (let k = i; k <= i + j; k++) {
fragment += fragments[k].sequence;
nbResidue += fragments[k].nbResidue;
}
let from = fragments[i].from + 1;
let to = fragments[i + j].to + 1;
if (fragment && nbResidue >= minResidue && nbResidue <= maxResidue) {
results.push(`H${fragment}OH$D${from}>${to}`);
}
}
}
return results;
}
// Combinatorial approach: generate all combinations of cleavage sites
const allResults = new Set();
for (let numDigestions = startDigestions; numDigestions <= effectiveMaxDigestions; numDigestions++) {
const combinations = (0, ml_spectra_processing_1.getCombinationsIterator)(numCleavages, numDigestions);
for (const cleavageSites of combinations) {
// Create fragments based on selected cleavage sites
const fragments = createFragmentsFromCleavages(allFragments, cleavageSites);
// Generate results with missed cleavages
for (let i = 0; i < fragments.length - minMissed; i++) {
for (let j = minMissed; j <= Math.min(maxMissed, fragments.length - i - 1); j++) {
let fragment = '';
let nbResidue = 0;
for (let k = i; k <= i + j; k++) {
fragment += fragments[k].sequence;
nbResidue += fragments[k].nbResidue;
}
let from = fragments[i].from + 1;
let to = fragments[i + j].to + 1;
if (fragment && nbResidue >= minResidue && nbResidue <= maxResidue) {
allResults.add(`H${fragment}OH$D${from}>${to}`);
}
}
}
}
}
return [...allResults];
}
/**
* Create fragments from selected cleavage sites.
* @param {string[]} allFragments - All possible fragments if all sites were cleaved.
* @param {number[]} cleavageSites - Indices of cleavage sites to use.
* @returns {Array<{sequence: string, nbResidue: number, from: number, to: number}>} Fragment objects.
*/
function createFragmentsFromCleavages(allFragments, cleavageSites) {
const fragments = [];
const cleavageSet = new Set(cleavageSites);
let currentFragment = '';
let fragmentStartIndex = 0;
for (let i = 0; i < allFragments.length; i++) {
currentFragment += allFragments[i];
// If this is a cleavage site or the last fragment, close the current fragment
if (cleavageSet.has(i) || i === allFragments.length - 1) {
const nbResidue = currentFragment
.replaceAll(/([A-Z][a-z]{2})/g, ' $1')
.split(/ /)
.filter(Boolean).length;
const from = fragmentStartIndex;
const to = from + nbResidue - 1;
fragments.push({
sequence: currentFragment,
nbResidue,
from,
to,
});
fragmentStartIndex = to + 1;
currentFragment = '';
}
}
return fragments;
}
function getRegexp(enzyme) {
switch (enzyme.toLowerCase().replaceAll(/[^\da-z]/g, '')) {
case 'chymotrypsin':
return /(Phe|Tyr|Trp)(?!Pro)/g;
case 'trypsin':
return /(Lys|Arg)(?!Pro)/g;
case 'lysc':
return /(Lys)(?!Pro)/g;
case 'glucph4':
return /(Glu)(?!Pro|Glu)/g;
case 'glucph8':
return /(Asp|Glu)(?!Pro|Glu)/g;
case 'thermolysin': // N-term of Leu, Phe, Val, Ile, Ala, Met
return /()(?=Ile|Leu|Val|Ala|Met|Phe)/g;
case 'cyanogenbromide':
return /(Met)/g;
case 'any':
return /()(?=[A-Z][a-z]{2})/g;
default:
throw new Error(`Digestion enzyme: ${enzyme} is unknown`);
}
}
//# sourceMappingURL=digestPeptide.js.map