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* Cis and trans per sequence, run.
*
* One pass, fed identically from the whole-file block or from the pixel table —
* the same two roads `run/coverage.ts` takes, and for the same reason: a
* marginal cannot be taken from one sequence's square, because a sequence's own
* block knows nothing about the contacts leaving it and a cis fraction computed
* from one comes out at exactly `1` everywhere.
*
* The arithmetic is `analysis/cistrans.ts`. What is here is which rows to show,
* which normalisation to show them in, which of the two fractions the bars
* stand for, and the three sentences a reader has to be told when the file does
* not permit the whole answer.
*/
import { DEFAULT_COUNT_COLUMN } from '../../metacooler/matrix'
import { binContigMap } from '../coverage'
import { SequenceContactAccumulator, transExpectation } from '../cistrans'
import {
boolParam,
contigIdsFor,
numParam,
strParam,
tickedSequences,
type TaskRunner,
} from '../job'
import { MATRIX_SEQUENCE_LIMIT } from '../tasks/cistrans'
import type {
CurveOutput,
CurveSeries,
MatrixOutput,
TableOutput,
TaskOutput,
} from '../types'
import { missingSequencesNote, validBins } from './blocks'
export const runCisTrans: TaskRunner = async (job) => {
const mc = job.mc
const balance = boolParam(job.params, 'balance', false)
const weights = validBins(mc, balance)
const contigs: Array<{ startBin: number; bins: number }> = []
for (let cid = 0; cid < mc.nContigs; cid++) {
const [from, to] = mc.contigExtent(cid)
contigs.push({ startBin: from, bins: Math.max(0, to - from) })
}
const contigOf = binContigMap(contigs, mc.nBins)
const accumulator = new SequenceContactAccumulator(mc.nContigs)
// Unanswered is every sequence and an empty list is nothing (§18.2): a run
// that never met a form — a stored session, a `chromosomix` line with no
// `--sequences` — is the whole file, and a reader who pressed **none** is
// told so rather than handed a whole-file answer. The estimate refuses that
// run before it is sent; this is what one that arrives anyway hears, and it
// hears it before the pass over the pixel table rather than after it.
const ticked = tickedSequences(job.params, 'sequences')
if (ticked !== null && ticked.length === 0) {
job.note('No sequence is ticked, so there is nothing to report.')
return []
}
const block = job.inputs.block
const wholeFileBlock =
block !== undefined &&
block.binsPerCell === 1 &&
job.framing.balance === balance &&
block.rowExtent[0] === 0 &&
block.rowExtent[1] === mc.nBins &&
block.colExtent[0] === 0 &&
block.colExtent[1] === mc.nBins
if (wholeFileBlock && block !== undefined) {
job.progress(0, 1, 'summing the block on screen')
// The block holds every off-diagonal pair twice, once at `(i, j)` and once
// at `(j, i)`, so only the upper triangle is walked. Adding both would double
// every trans total *and* every trans expectation, which cancels in the
// enrichment and does not cancel in the table.
for (let r = 0; r < block.nrows; r++) {
job.throwIfCancelled()
const row = r * block.ncols
for (let c = r; c < block.ncols; c++) {
const value = block.values[row + c]
if (value === 0) continue
accumulator.add(contigOf[r], contigOf[c], value)
}
}
} else {
if (job.framing.value !== '' && job.framing.value !== DEFAULT_COUNT_COLUMN) {
job.note(
`The map is drawn from the ${job.framing.value} column, but a whole-file pass reads ` +
`${DEFAULT_COUNT_COLUMN}. These numbers are of the counts.`,
)
}
job.progress(0, 1, 'reading pixels')
await mc.scanPixels({
onChunk: (chunk) => {
job.throwIfCancelled()
for (let i = 0; i < chunk.length; i++) {
const bin1 = chunk.bin1[i]
const bin2 = chunk.bin2[i]
const raw = chunk.count[i]
accumulator.add(
contigOf[bin1],
contigOf[bin2],
weights === null ? raw : raw * weights[bin1] * weights[bin2],
)
}
return true
},
onProgress: (done, total) => job.progress(done, total, 'reading pixels'),
})
}
job.throwIfCancelled()
if (accumulator.pairsOverflowed) {
job.note(
'This file has more sequence pairs with contact than the pair table holds, so the ranked ' +
'list below is of the pairs seen first rather than of the strongest. The per-sequence ' +
// Not *or read it as a metagenome*: this runs in a worker, which cannot
// know whether the page shows that format (§29), and the advice is a
// file the reader would have to make rather than a thing they can do.
'rows are unaffected. Tick fewer sequences.',
)
}
if (accumulator.dropped > 0) {
job.note(
`${Math.round(accumulator.dropped).toLocaleString()} contacts have an end outside every ` +
'sequence and are left out. A bin belonging to no contig means the bin table and the ' +
'contig table disagree about this file.',
)
}
// Which rows are reported: every sequence where the run was never asked, and
// the ticked ones this file has where it was — the pass above read the whole
// file either way. A ticked name this file has not got is named and left out
// (§5.9), and a list of nothing but those is said as that, not as nothing
// ticked.
let shown: number[]
if (ticked === null) {
shown = contigs.map((_contig, cid) => cid)
} else {
const found = contigIdsFor(mc, ticked)
const said = missingSequencesNote(mc, found.missing, found.ids.length)
if (said !== null) job.note(said)
shown = found.ids
}
if (shown.length === 0) return []
const rows = shown.map((cid) => {
const cis = accumulator.cis[cid]
const trans = accumulator.trans[cid]
const total = cis + trans
return {
sequence: mc.chromnames[cid],
bins: contigs[cid].bins,
cis,
trans,
total,
// Zero of zero is not zero: a sequence with no contact at all has no cis
// fraction, and sorting it among the genuinely trans-heavy ones would be
// the most misleading possible reading of no data.
fraction: total > 0 ? cis / total : Number.NaN,
ratio: cis > 0 ? trans / cis : Number.NaN,
perBin: contigs[cid].bins > 0 ? total / contigs[cid].bins : Number.NaN,
}
})
const outputs: TaskOutput[] = [
{
kind: 'table',
id: 'cistrans',
label: 'Cis and trans per sequence',
columns: [
{ key: 'sequence', label: 'Sequence', kind: 'text' },
{ key: 'bins', label: 'Bins', kind: 'number', digits: 0 },
{ key: 'cis', label: 'Cis', kind: 'number', digits: 0 },
{ key: 'trans', label: 'Trans', kind: 'number', digits: 0 },
{ key: 'total', label: 'Total', kind: 'number', digits: 0 },
{
key: 'fraction',
label: 'Cis fraction',
kind: 'number',
digits: 3,
hint: 'Of the contacts touching this sequence, how many stay on it.',
},
{ key: 'ratio', label: 'Trans / cis', kind: 'number', digits: 3 },
{ key: 'perBin', label: 'Contacts per bin', kind: 'number', digits: 2 },
],
// In the file's own order rather than ranked, because the file's order is
// the one the map is drawn in and this table is read beside it.
rows,
} satisfies TableOutput,
fractionBars(rows, strParam(job.params, 'bars', 'cis')),
]
const mode = strParam(job.params, 'normalise', 'enrichment')
const minContacts = Math.max(0, numParam(job.params, 'minContacts', 10))
const maxEdges = Math.max(10, Math.round(numParam(job.params, 'maxEdges', 500)))
const expectedOf = transExpectation(accumulator.trans, accumulator.transTotal)
const valueOf = (a: number, b: number, raw: number): number => {
if (mode === 'raw') return raw
if (mode === 'bins') {
const cells = contigs[a].bins * contigs[b].bins
return cells > 0 ? raw / cells : Number.NaN
}
const expected = expectedOf(a, b)
return expected > 0 ? raw / expected : Number.NaN
}
const inShown = new Set(shown)
const edges: Array<{ a: string; b: string; raw: number; value: number; expected: number }> = []
for (const [a, b, raw] of accumulator.pairs()) {
if (!inShown.has(a) || !inShown.has(b)) continue
if (raw < minContacts) continue
const value = valueOf(a, b, raw)
if (!Number.isFinite(value)) continue
edges.push({
a: mc.chromnames[a],
b: mc.chromnames[b],
raw,
value,
expected: expectedOf(a, b),
})
}
edges.sort((x, y) => y.value - x.value)
if (edges.length > 0) {
outputs.push({
kind: 'table',
id: 'cistrans-pairs',
label:
mode === 'enrichment'
? 'Sequence pairs, against indifference'
: 'Sequence pairs, ranked',
columns: [
{ key: 'a', label: 'Sequence', kind: 'text' },
{ key: 'b', label: 'Sequence', kind: 'text' },
{ key: 'raw', label: 'Contacts', kind: 'number', digits: 0 },
...(mode === 'enrichment'
? [
{
key: 'expected',
label: 'Expected',
kind: 'number' as const,
digits: 1,
hint: 'From the two sequences’ own trans coverage, under indifference.',
},
]
: []),
{
key: 'value',
label:
mode === 'raw' ? 'Contacts' : mode === 'bins' ? 'Per bin pair' : 'Observed / expected',
kind: 'number',
digits: mode === 'raw' ? 0 : mode === 'bins' ? 5 : 2,
},
],
rows: edges.slice(0, maxEdges),
} satisfies TableOutput)
if (edges.length > maxEdges) {
job.note(
`${edges.length.toLocaleString()} sequence pairs pass the threshold and the strongest ` +
`${maxEdges.toLocaleString()} are listed. Raise “pairs to list” to see more.`,
)
}
}
if (boolParam(job.params, 'matrix', true)) {
if (shown.length > MATRIX_SEQUENCE_LIMIT) {
job.note(
`${shown.length.toLocaleString()} sequences is past the ` +
`${MATRIX_SEQUENCE_LIMIT.toLocaleString()} this draws a square for, so the ranked ` +
'table above is the answer. Tick fewer sequences for the picture.',
)
} else {
const m = shown.length
const values = new Float32Array(m * m)
for (let r = 0; r < m; r++) {
for (let c = 0; c < m; c++) {
const a = shown[r]
const b = shown[c]
// The diagonal is the sequence's own cis contact, which is a different
// quantity from every other cell and is left out rather than drawn: on
// any real map it is one to three orders of magnitude above the trans
// cells, so including it sets the colour scale and turns the square
// into a picture of its own diagonal.
values[r * m + c] = a === b ? Number.NaN : valueOf(a, b, accumulator.pair(a, b))
}
}
const ticks = m <= 40 ? shown.map((cid) => mc.chromnames[cid]) : []
outputs.push({
kind: 'matrix',
id: 'cistrans-matrix',
label:
mode === 'enrichment'
? 'Between sequences, against indifference'
: 'Between sequences',
nrows: m,
ncols: m,
values,
xLabel: 'Sequence',
yLabel: 'Sequence',
xTicks: ticks,
yTicks: ticks,
colormap: mode === 'enrichment' ? 'RdBu_r' : 'default',
...(mode === 'enrichment' ? { centre: 1 } : {}),
} satisfies MatrixOutput)
}
}
return outputs
}
/** What the bars read off the per-sequence table; structurally its rows. */
interface SequenceRow {
sequence: string
cis: number
trans: number
total: number
}
/** The stack the two fractions share, where the reader asked for both. */
const CONTACT_STACK = 'contacts'
/**
* The per-sequence fractions, as one bar per sequence.
*
* The numbers are the table's own and the picture is the point. A column
* reading `0.994, 0.991, 0.987, 0.612, 0.989` is a list a reader has to scan
* and subtract; the same numbers as bars in the file's order put the one
* sequence that is a third trans a head below its neighbours before anybody has
* read a digit — and on a metagenome, where the table is four thousand rows
* long, that is the difference between a record and an answer.
*
* **Fractions rather than counts**, and that is the whole of why this is worth
* drawing. A bar of each sequence's cis *contacts* is a picture of how long the
* sequences are: chromosome I gets a stub and chromosome IV a tower, on any file
* whatever, because a longer sequence holds more of everything. Dividing by what
* the sequence has in total takes the length back out and leaves the quantity
* the task is named for, which is comparable from one sequence to the next and
* from one library to the next.
*
* A sequence with no contact at all gets a **gap**, not a zero bar: zero of zero
* is not zero, which is the same rule its row in the table keeps.
*
* And there is no ceiling on the number of bars, unlike the square
* ({@link MATRIX_SEQUENCE_LIMIT}). A square goes from a picture to a grey band
* because its cells shrink in both directions at once; a row of four thousand
* bars is a silhouette of the same shape, still read the same way, and the mark
* control turns it into the line that silhouette already is.
*/
function fractionBars(rows: readonly SequenceRow[], which: string): CurveOutput {
// Each half against the sequence's own total rather than one of them against
// `1 - other`: the two are the same number to within a float, and computing
// one by subtraction would hand a sequence with no contact a fraction of 1.
const share = (part: number, total: number): number =>
total > 0 ? part / total : Number.NaN
// One abscissa for both series rather than two copies of it: they are the same
// bars, and the worker's transfer list already expects two views of one buffer
// (`worker/protocol.analysisTransfers`, which a profile and its extent share).
const at = Float64Array.from(rows, (_row, index) => index)
const both = which === 'both'
const cis: CurveSeries = {
name: 'cis',
x: at,
y: Float64Array.from(rows, (row) => share(row.cis, row.total)),
mark: 'bars',
...(both ? { stack: CONTACT_STACK } : {}),
}
const trans: CurveSeries = {
name: 'trans',
x: at,
y: Float64Array.from(rows, (row) => share(row.trans, row.total)),
mark: 'bars',
...(both ? { stack: CONTACT_STACK } : {}),
}
return {
kind: 'curve',
id: 'cistrans-fractions',
label: both
? 'Cis and trans fraction per sequence'
: which === 'trans'
? 'Trans fraction per sequence'
: 'Cis fraction per sequence',
series: both ? [cis, trans] : [which === 'trans' ? trans : cis],
xLabel: 'Sequence',
// Per cent, which is how §26.2 has a fraction said on a surface that
// summarises it; the values behind the axis stay fractions, so the TSV holds
// the `0.994` the table holds.
yLabel: 'Share of the sequence’s contacts (%)',
xScale: 'linear',
yScale: 'linear',
// The whole of a fraction, rather than the part these fractions happen to
// occupy. Fitted, an axis over `0.987` to `0.994` draws seven parts in a
// thousand as the height of the picture and two libraries that agree as two
// that do not — and it would put each run of this task against a ceiling of
// its own. A default like every other declared window (§18.7): the marquee
// and the boxes still move it.
yDomain: [0, 1],
// The sequences, in the file's own order, from where every other output
// takes them. One name per bar, so the axis names the bar under the pointer
// rather than counting them.
xTicks: rows.map((row) => row.sequence),
}
}
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