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mutationVector.js
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mutationVector.js
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// Domain logic for mutation datasets.
var _ = require('../underscore_ext').default;
var widgets = require('../columnWidgets');
var xenaQuery = require('../xenaQuery');
var Rx = require('../rx').default;
var exonLayout = require('../exonLayout');
var intervalTree = require('static-interval-tree');
var {pxTransformInterval} = require('../layoutPlot');
var {hexToRGB, colorStr} = require('../color_helper').default;
var jStat = require('jStat').jStat;
var parsePos = require('../parsePos');
import sortOrder from './sparseSortOrder';
//function groupedLegend(colorMap, valsInData) { //eslint-disable-line no-unused-vars
// var inData = new Set(valsInData),
// groups = _.groupBy(
// _.filter(_.keys(colorMap), val => inData.has(val)), k => colorMap[k]),
// colors = _.keys(groups);
// return {
// colors,
// labels: _.map(colors, c => groups[c].join(', ')),
// align: 'left'
// };
//}
//
//function sortedLegend(colorMap, valsInData) { //eslint-disable-line no-unused-vars
// var inData = new Set(valsInData),
// colorList = _.filter(_.pairs(colorMap), ([val]) => inData.has(val))
// .sort(([, c0], [, c1]) => c0 > c1 ? -1 : 1);
// return {
// colors: _.pluck(colorList, 1),
// labels: _.pluck(colorList, 0),
// align: 'left'
// };
//}
var colors = {
categoryMutation: [
["#9b9b9b", 'Intron/RNA'], // darker grey code: 0
["#2CA02C", 'Silent'], // green code:1
["#1F77B4", 'Missense/Inframe'], // blue code:2
["#FF7F0E", 'Splice'], // orange code:3
["#D62728", 'Deleterious'], // red code:4
["#c5b0d5", "Complex/Other/Unannotated"] // light lavender missing/no code
],
af: {r: 255, g: 0, b: 0},
SVdefaultColor: "#c5b0d5", // light lavender
missing: "#c5b0d5" // light lavender for no impact annotation or annotation outside of impact code
};
var getSNVEffect = (colorMap, effect) => { // match case insensitive, beginning of word
var effectKey = _.keys(colorMap).find(key => {
var patt = new RegExp('^' + key, "i");
return patt.test(effect);
});
return effectKey;
};
function impactLegend(colorMap, valsInData) {
var missing = _.filter(valsInData, v => !getSNVEffect(colorMap, v)),
colorList = _.filter(_.pairs(colorMap), ([val]) => {
var patt = new RegExp('^' + val, "i");
return valsInData.find(effect => patt.test(effect));
}).reverse(); // Legend reverses
if (missing.length !== 0) {
colorList = _.merge(colorList, [["unannotated", colors.missing]]);
}
//groupBy color
let colorGroups = _.mapObject(_.groupBy(colorList, ([, color]) => color), (val) => _.pluck(val, 0)),
mutationColors = _.keys(colorGroups), // color square
titles = _.values(colorGroups).map(impactList => impactList.join("\n")), // mouse over text
labels = mutationColors.map(color => _.find(colors.categoryMutation, ([c, ]) => color === c)[1]); //visible text
return {
colors: mutationColors,
titles: titles,
labels: labels,
};
}
var impact = {
//destroy protein, color red
'Nonsense': 4,
'stop_gained': 4,
'Frameshift': 4,
'Frame_Shift': 4,
'De_novo_Start_OutOfFrame': 4,
//splice related, color orange
'splice': 3,
//modify protein, color blue
'missense': 2,
'NON_SYNONYMOUS': 2,
'NONSYNONYMOUS': 2,
'MultiAAMissense': 2,
'start_lost': 2,
'start_gained': 2,
'STOP_LOST': 2,
'Nonstop_Mutation': 2,
'Translation_Start_Site': 2,
'CdsStartSNV': 2,
'De_novo_Start_InFrame': 2,
'initiator_codon': 2,
'5_prime_UTR_premature_start_codon_gain': 2,
'disruptive_inframe_deletion': 2,
'disruptive_inframe_insertion': 2,
'inframe': 2,
'In_Frame': 2,
'CODON': 2,
//do not modify protein, color green
'Synonymous': 1,
'Silent': 1,
'stop_retained': 1,
'TF_BINDING_SITE': 1,
//mutations effect we don't know, default color grey
'lincRNA': 0,
'RNA': 0,
'exon_variant': 0,
'NON_CODING_EXON': 0,
'upstream': 0,
'downstream': 0,
"5'Flank": 0,
"3'Flank": 0,
"3'UTR": 0,
"5'UTR": 0,
'UTR_3_PRIME': 0,
'UTR_5_PRIME': 0,
'5_prime_UTR': 0,
'3_prime_UTR': 0,
'intron': 0,
'intergenic': 0,
'IGR': 0,
'INTRAGENIC': 0
},
chromColorGB = { //genome browser chrom coloring
"1": "#996600",
"2": "#666600",
"3": "#99991E",
"4": "#CC0000",
"5": "#FF0000",
"6": "#FF00CC",
"7": "#FFCCCC",
"8": "#3FF990",
"9": "#FFCC00",
"10": "#FFFF00",
"11": "#CCFF00",
"12": "#00FF00",
"13": "#358000",
"14": "#0000CC",
"15": "#6699FF",
"16": "#99CCFF",
"17": "#00FFFF",
"18": "#CCFFFF",
"19": "#9900CC",
"20": "#CC33FF",
"21": "#CC99FF",
"22": "#666666",
"X": "#999999",
"Y": "#CCCCCC",
"M": "#CCCC99"
},
chromColorPCAWG = { // PCAWG chrom coloring
"1": "#DE47AB",
"2": "#72BE97",
"3": "#F7F797",
"4": "#7C749B",
"5": "#E85726",
"6": "#B395F8",
"7": "#DC8747",
"8": "#96D53D",
"9": "#DC85EE",
"10": "#7D32B3",
"11": "#88DB68",
"12": "#78AAF1",
"13": "#D9C6CA",
"14": "#336C80",
"15": "#F7CA44",
"16": "#32C7C7",
"17": "#D4C5F2",
"18": "#995493",
"19": "#F88B78",
"20": "#475ECC",
"21": "#E0BD8C",
"22": "#9E2800",
"X": "#F2BBD2",
"Y": "#B6EBEA"
},
impactColor = _.mapObject(impact, i => colors.categoryMutation[i][0]),
saveUndef = f => v => v == null ? v : f(v),
round = Math.round,
decimateFreq = saveUndef(v => round(v * 31) / 32), // reduce to 32 vals
vafLegend = () => ({
colors: [0, 0.5, 1].map(a => colorStr({...colors.af, a})),
labels: ['0%', '50%', '100%'],
align: 'center'
}),
getSVLegend = chromColorMap => ({
// have to explicitly call hexToRGB to avoid map passing in index.
colors: chromColorMap ?
_.values(chromColorMap).map(h => hexToRGB(h)).map(colorStr).reverse() :
[colors.SVdefaultColor],
labels: chromColorMap ? _.keys(chromColorMap).map(key => "chr" + key).reverse() :
['structural variant'],
align: 'left'
}),
features = {
impact: {
get: v => v.effect,
color: (colorMap, v) => colorMap[getSNVEffect(colorMap, v)] || colors.missing,
legend: impactLegend
},
// dna_vaf and rna_vaf need to be updated to reflect the call params.
'dna_vaf': {
get: v => v.dna_vaf == null ? undefined : decimateFreq(v.dna_vaf),
color: v => colorStr(v == null ? colors.missing : _.assoc(colors.af, 'a', v)),
legend: vafLegend
},
'rna_vaf': {
get: v => v.rna_vaf == null ? undefined : decimateFreq(v.rna_vaf),
color: v => colorStr(v == null ? colors.missing : _.assoc(colors.af, 'a', v)),
legend: vafLegend
}
};
function chromFromAlt(alt) {
var start = alt.search(/[\[\]]/),
end = alt.search(":");
return alt.slice(start + 1, end).replace(/chr/i, "");
}
function posFromAlt(alt) {
var end = alt.search(/[\[\]\A\T\G\C]{1,2}$/),
start = alt.search(":");
return alt.slice(start + 1, end);
}
function structuralVariantClass(alt) {
var firstBase = _.first(alt),
lastBase = _.last(alt);
return firstBase === '[' || firstBase === ']' ? 'left' :
(lastBase === '[' || lastBase === ']' ? 'right' : null);
}
function joinedVariantDirection(alt) {
var firstBase = _.first(alt),
lastBase = _.last(alt);
return firstBase === ']' || lastBase === ']' ? 'left' :
(firstBase === '[' || lastBase === '[' ? 'right' : null);
}
var getExonPadding = mutationDataType => {
if (mutationDataType === "SV") {
return {
padTxStart: 2000,
padTxEnd: 0
};
} else if (mutationDataType === "mutation") {
return {
padTxStart: 1000,
padTxEnd: 1000
};
} else {
return {
padTxStart: 1000,
padTxEnd: 1000
};
}
};
function evalMut(flip, mut) {
return {
// impact: features.impact.get(mut),
right: flip ? -mut.end : mut.start
};
}
function cmpMut(mut1, mut2) {
/*
if (mut1.impact !== mut2.impact) {
if (mut1.impact === undefined){
return 1;
} else if (mut2.impact === undefined) {
return -1;
} else {
return mut2.impact - mut1.impact; // high impact sorts first
}
}
*/
return mut1.right - mut2.right; // low coord sorts first
}
function rowOrder(row1, row2, flip) {
var row1a, row2a;
// Native map is a lot faster than _.map. Need an es5 polyfill, or
// perhaps lodash, or ramda.
row1a = row1.map(m => evalMut(flip, m));
row2a = row2.map(m => evalMut(flip, m));
return cmpMut(_.maxWith(row1a, cmpMut), _.maxWith(row2a, cmpMut));
}
function cmpRowOrNoVariants(v1, v2, xzoom, flip) {
var vf1 = v1.filter(v => v.start <= xzoom.end && v.end >= xzoom.start),
vf2 = v2.filter(v => v.start <= xzoom.end && v.end >= xzoom.start);
if (vf1.length === 0) {
return (vf2.length === 0) ? 0 : 1;
}
return (vf2.length === 0) ? -1 : rowOrder(vf1, vf2, flip);
}
function cmpRowOrNull(v1, v2, xzoom, flip) {
if (v1 == null) {
return (v2 == null) ? 0 : 1;
}
return (v2 == null) ? -1 : cmpRowOrNoVariants(v1, v2, xzoom, flip);
}
function cmpSamples(xzoom, sample, flip, s1, s2) {
return cmpRowOrNull(sample[s1], sample[s2], xzoom, flip);
}
// XXX Instead of checking strand here, it should be set as a column
// property as part of the user input: flip if user enters a gene on
// negative strand. Don't flip for genomic range view, or positive strand.
function cmp(column, data, index) {
var {fields: [field], xzoom, sortVisible} = column,
pos = parsePos(field),
appliedZoom = sortVisible && xzoom ? xzoom : {start: -Infinity, end: Infinity},
refGene = _.getIn(data, ['refGene']),
flip = !pos && refGene && _.getIn(_.values(refGene), [0, 'strand']) === '-',
samples = _.getIn(index, ['bySample']);
return samples ?
(s1, s2) => cmpSamples(appliedZoom, samples, flip, s1, s2) :
() => 0;
}
var {sparseDataRange, refGeneRange} = xenaQuery;
// XXX Might want to optimize this before committing. We could mutate in-place
// without affecting anyone. This may be slow for large mutation datasets.
//
// Map sampleIDs to index into 'samples' array.
function mapSamples(samples, data) {
var sampleMap = _.object(samples, _.range(samples.length));
return _.updateIn(data,
['req', 'rows'], rows => _.map(rows,
row => _.assoc(row, 'sample', sampleMap[row.sample])),
['req', 'samplesInResp'], sIR => _.map(sIR, s => sampleMap[s]));
}
//user input is a gene, get the mutations by the gene's genomic coordinates
function fetchGeneByCoordinate({dsID, fields, fieldType, assembly}, samples) {
var {name, host} = xenaQuery.refGene[assembly] || {};
return name ? xenaQuery.refGeneExons(host, name, fields)
.flatMap(refGene => {
var coords = _.values(refGene)[0];
if (!coords) {
return Rx.Observable.of(null);
}
var {txStart, txEnd, chrom} = coords,
{padTxStart, padTxEnd} = getExonPadding(fieldType);
return sparseDataRange(dsID, samples, chrom, txStart - padTxStart, txEnd + padTxEnd)
.map(req => mapSamples(samples, {req, refGene}));
}) : Rx.Observable.of(null);
}
/*
//user input is a gene, get the mutations by gene annotation that comes with the data
var {sparseData} = xenaQuery;
function fetchGeneByAnnotation({dsID, fields, assembly}, [samples]) {
var {name, host} = xenaQuery.refGene[assembly] || {};
return Rx.Observable.zipArray(
sparseData(dsID, samples, fields[0]),
name ? xenaQuery.refGeneExonCase(host, name, fields) : Rx.Observable.of({})
).map(resp => mapSamples(samples, _.object(['req', 'refGene'], resp)));
}*/
function fetchChrom({dsID, assembly}, samples, pos) {
var {name, host} = xenaQuery.refGene[assembly] || {};
return refGeneRange(host, name, pos.chrom, pos.baseStart, pos.baseEnd)
.flatMap(refGene =>
sparseDataRange(dsID, samples, pos.chrom, pos.baseStart, pos.baseEnd)
.map(req => mapSamples(samples, {req, refGene})));
}
function fetch(column, cohortSamples) {
var pos = parsePos(column.fields[0]),
method = pos ? fetchChrom : fetchGeneByCoordinate;
return method(column, cohortSamples, pos);
}
// Group by, returning groups in sorted order. Scales O(n) vs.
// sort's O(n log n), if the number of values is much smaller than
// the number of elements.
function sortByGroup(arr, keyfn) {
var grouped = _.groupBy(arr, keyfn);
return _.map(_.sortBy(_.keys(grouped), _.identity),
k => grouped[k]);
}
function findSNVNodes(byPosition, layout, colorMap, feature, samples) {
var sindex = _.object(samples, _.range(samples.length)),
{get, color} = features[feature],
minSize = ([s, e]) => [s, e - s < 1 ? s + 1 : e],
// sortfn is about 2x faster than sortBy, for large sets of variants
sortfn = (coll, keyfn) => _.flatten(sortByGroup(coll, keyfn), true);
// _.uniq is something like O(n^2). Using ES6 Set, which should be more like O(n).
var matches = _.groupBy([...new Set(_.flatmap(layout.chrom,
([start, end]) => intervalTree.matches(byPosition, {start, end})))],
v => v.variant.sample);
return _.flatmap(matches, vars => {
var count = vars.length;
return sortfn(vars.map((v, i) => {
var [xStart, xEnd] = minSize(pxTransformInterval(layout, [v.start, v.end]));
return {
xStart,
xEnd,
y: sindex[v.variant.sample],
color: color(colorMap, get(v.variant)), // needed for sort, before drawing.
subrow: i,
rowCount: count,
data: v.variant
};
}), v => v.color);
});
}
function findSVNodes(byPosition, layout, colorMap, samples) {
var sindex = _.object(samples, _.range(samples.length)),
minSize = ([s, e]) => [s, e - s < 1 ? s + 1 : e];
// _.uniq is something like O(n^2). Using ES6 Set, which should be more like O(n).
var matches = _.groupBy([...new Set(_.flatmap(layout.chrom,
([start, end]) => intervalTree.matches(byPosition, {start, end})))],
v => v.variant.sample);
return _.flatmap(matches, vars => {
var count = vars.length;
return vars.map((v, i) => {
var [xStart, xEnd] = minSize(pxTransformInterval(layout, [v.start, v.end])),
y = sindex[v.variant.sample],
{chr, alt} = v.variant;
return {
xStart,
xEnd,
y,
color: colorMap ?
colorMap[chromFromAlt(alt)] || colorMap[chr.replace(/chr/i, "")] || colors.SVdefaultColor :
colors.SVdefaultColor,
subrow: i,
rowCount: count,
data: v.variant
};
});
});
}
var swapIf = (strand, [x, y]) => strand === '-' ? [y, x] : [x, y];
function defaultXZoom(pos, refGene, type) {
if (pos) { // User supplied chrom position
return {
start: pos.baseStart,
end: pos.baseEnd
};
}
var {txStart, txEnd, strand} = refGene,
{padTxStart, padTxEnd} = getExonPadding(type),
[startPad, endPad] = swapIf(strand, [padTxStart, padTxEnd]);
return {
start: txStart - startPad,
end: txEnd + endPad
};
}
var getCustomColor = (dataset, type) =>
_.getIn(dataset, ['customcolor', type], impactColor);
function svDataToDisplay(column, vizSettings, data, sortedSamples, index) {
var pos = parsePos(column.fields[0]);
if (_.isEmpty(data) || _.isEmpty(data.req) || (!pos && _.isEmpty(data.refGene))) {
return {};
}
var colorMapping = {
"chromosomeGB": chromColorGB,
"chromosomePCAWG": chromColorPCAWG
};
var getColorMapping = svColor => colorMapping[svColor];
var refGeneObj = _.values(data.refGene)[0],
maxXZoom = defaultXZoom(pos, refGeneObj, 'SV'), // exported for zoom controls
{width, showIntrons = false, xzoom = maxXZoom} = column,
createLayout = pos ? exonLayout.chromLayout : (showIntrons ? exonLayout.intronLayout : exonLayout.layout),
layout = createLayout(refGeneObj, width, xzoom, pos),
colorMap = (vizSettings && vizSettings.svColor) ?
getColorMapping(vizSettings.svColor) : undefined,
//function to get custom color from metadata: getCustomColor(column.fieldSpecs, datasets, 'SV'),
nodes = findSVNodes(index.byPosition, layout, colorMap, sortedSamples);
return {
layout,
nodes,
maxXZoom,
legend: getSVLegend(colorMap)
};
}
function snvDataToDisplay(column, vizSettings, data, sortedSamples, index) {
var pos = parsePos(column.fields[0]);
if (_.isEmpty(data) || _.isEmpty(data.req) || (!pos && _.isEmpty(data.refGene))) {
return {};
}
var refGeneObj = _.values(data.refGene)[0],
maxXZoom = defaultXZoom(pos, refGeneObj, 'mutation'), // exported for zoom controls
{dataset, width, showIntrons = false,
sFeature = 'impact', xzoom = maxXZoom} = column,
allVals = _.uniq(data.req.rows.map(features[sFeature].get)),
createLayout = pos ? exonLayout.chromLayout : (showIntrons ? exonLayout.intronLayout : exonLayout.layout),
layout = createLayout(refGeneObj, width, xzoom, pos),
colorMap = getCustomColor(dataset, 'SNV'),
nodes = findSNVNodes(index.byPosition, layout, colorMap, sFeature, sortedSamples);
return {
layout,
nodes,
maxXZoom,
legend: features[sFeature].legend(colorMap, allVals)
};
}
function index(fieldType, data) {
if (!_.get(data, 'req')) {
return null;
}
var {req: {rows, samplesInResp}} = data,
bySample = _.groupBy(rows, 'sample'),
empty = []; // use a single empty object.
rows = rows.map(row => {
var alt = row.alt,
virtualStart = row.start,
virtualEnd = row.end;
if (row.start === row.end) { // SV vcf starndard: start is equal to end position
let vclass = structuralVariantClass(alt);
if (vclass === 'left') {
//SV: new segment to the left
virtualStart = -Infinity;
} else if (vclass === 'right') {
//SV: new segment on the right
virtualEnd = Infinity;
}
}
return {
start: virtualStart,
end: virtualEnd,
variant: row
};
});
return {
byPosition: intervalTree.index(rows),
bySample: _.object(
samplesInResp,
samplesInResp.map(s => bySample[s] || empty))
};
}
// SNV P value calculation is an approximation Jing's got from the internet, it is not tested against the exact calculation.
// it is ok to use in the mupit viz, but not confident it can be used to represent the true p value
// in addition, the K value should be the size of the gene coding region, or gene's exon region, or the size of the whole gene including introns, currently set as 1000.
function SNVPvalue (rows, total, k) {
//total: instances, like total number of people in the experiments
//k: possible variaty, like 365 days for birthday
let newRows = _.map(rows, n => `${n.chr}:${n.start}`);
return _.values(_.mapObject(_.countBy(newRows, n => n),
function (val, key) {
// a classic birthday problem: https://en.wikipedia.org/wiki/Birthday_problem
// a strong birthday problem: extend to trio (at least a trio) or Quadruple (at least four) etc
// Journal of Statistical Planning and Inference 130 (2005) 377 – 389 https://www.math.ucdavis.edu/~tracy/courses/math135A/UsefullCourseMaterial/birthday.pdf
// Poisson approximation
// http://math.stackexchange.com/questions/25876/probability-of-3-people-in-a-room-of-30-having-the-same-birthday/25880#25880
// no. 28
// simulation: http://www.drmoron.org/3-birthday-problem/
// total = 30;
// val = 4;
// k = 365;
// result ≈0.028537
// P(365,30,3)≃2,85%
// P(365,30,4)≃0,0532%
var T = jStat.combination(total, val) / Math.pow(k, (val - 1)),
pValue = 1 - (Math.exp(-T) + Math.exp( - (T / (1 + val * (total - val) / (2 * k))))) / 2, // no 28
//pValue2 = 1 - Math.exp(- jStat.combination(total, val) / Math.pow(k, (val - 1))); //no 51
[chr, start] = key.split(':');
return {
chr: chr,
start: start,
total: total,
class: k,
count: val,
pValue: pValue
};
}
));
}
////////////////////////////////
// download of on-screen data
function makeRow(fields, sampleGroup, row) {
let fieldValue;
if (_.isArray(sampleGroup) && sampleGroup.length === 0) {
fieldValue = 'no variant';
}
if (_.isEmpty(sampleGroup)) {
sampleGroup = [row];
}
return _.flatmap(sampleGroup, row =>
_.map(fields, f => (row && row[f]) || fieldValue));
}
function getRowFields(rows, sampleGroups) {
if (_.isEmpty(sampleGroups)) {
return []; // When no samples exist
} else if (!_.isEmpty(rows)) {
return _.keys(rows[0]); // When samples have mutation(s)
} else {
return ['sample', 'result']; // default fields for mutation-less columns
}
}
function formatSamples(sampleFormat, rows) {
return rows ? _.map(rows, r => _.updateIn(r, ['sample'], sampleFormat)) : rows;
}
function download({data: {req: {rows}}, samples, index, sampleFormat}) {
let groupedSamples = _.getIn(index, ['bySample']) || [],
rowFields = getRowFields(rows, groupedSamples),
allRows = _.map(samples, (sId) => {
let alternateRow = {sample: sampleFormat(sId)}; // only used for mutation-less samples
return makeRow(rowFields, formatSamples(sampleFormat, groupedSamples[sId]),
alternateRow);
});
return [rowFields, allRows];
}
widgets.cmp.add('mutation', cmp);
widgets.index.add('mutation', index);
widgets.data.add('mutation', sortOrder(cmp));
widgets.transform.add('mutation', snvDataToDisplay);
widgets.download.add('mutation', download);
widgets.cmp.add('SV', cmp);
widgets.index.add('SV', index);
widgets.data.add('SV', sortOrder(cmp));
widgets.transform.add('SV', svDataToDisplay);
widgets.download.add('SV', download);
module.exports = {
features,
chromFromAlt,
posFromAlt,
structuralVariantClass,
joinedVariantDirection,
chromColorGB,
SNVPvalue,
fetch,
impact,
getSNVEffect
};