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* Per-cell contact QC, run.
*
* One pass per cell, through `MetaCooler.scanCells` — which is `scanAll` with
* the chunks told which cell they came out of, and costs exactly what summing
* the same cells costs (§3.8).
*
* The arithmetic is a histogram of separations with three edges in it, and the
* only thing worth care is *which denominator*. Nagano's percentages are of
* **all** of a cell's contacts, trans included, rather than of its cis ones — a
* cell whose trans fraction is enormous is a cell with a problem, and hiding
* that by normalising it away would make the very cells the QC is for look
* ordinary. So the bands are fractions of the total, and the cis fraction is a
* column of its own beside them.
*/
import { binContigMap } from '../coverage'
import { boolParam, numParam, strParam, type TaskRunner } from '../job'
import { MITOTIC_TO, NEAR_FROM, NEAR_TO } from '../tasks/cellqc'
import type { CurveOutput, TableOutput, TaskOutput } from '../types'
import { validBins } from './blocks'
/** What one cell's pixels add up to. */
interface CellTotals {
contacts: number
nnz: number
cis: number
trans: number
/** Cis contacts below the near band. */
short: number
near: number
mitotic: number
/** Cis contacts beyond the mitotic band. */
far: number
}
export const runCellQc: TaskRunner = async (job) => {
const mc = job.mc
if (mc.cells.length === 0) {
job.note('This file has no cells, so there is nothing to measure per cell.')
return []
}
// **The whole file by default**, and it is restored afterwards. The reader's
// ticked set is the thing this task exists to help them choose, so measuring
// only what they have already ticked answers a question they have already
// answered. The mount is this worker's own (§18.3), so re-selecting here
// cannot disturb the map on screen — but a later task on the same mount would
// inherit whatever was left behind, which is why it is put back.
const everyCell = strParam(job.params, 'cells', 'all') !== 'selected'
const ticked = mc.activeCells
if (everyCell) mc.selectCells(null)
try {
return await measure(job, ticked)
} finally {
if (everyCell) mc.selectCells(ticked)
}
}
async function measure(
job: Parameters<TaskRunner>[0],
ticked: readonly string[],
): Promise<TaskOutput[]> {
const mc = job.mc
const names = mc.activeCells
const balance = boolParam(job.params, 'balance', false)
const weights = validBins(mc, balance)
const contigs: Array<{ startBin: number; bins: number }> = []
let longest = 0
for (let cid = 0; cid < mc.nContigs; cid++) {
const [from, to] = mc.contigExtent(cid)
contigs.push({ startBin: from, bins: Math.max(0, to - from) })
longest = Math.max(longest, (to - from) * mc.binsize)
}
const contigOf = binContigMap(contigs, mc.nBins)
const nearFrom = Math.max(0, numParam(job.params, 'nearFrom', NEAR_FROM))
const nearTo = Math.max(nearFrom + 1, numParam(job.params, 'nearTo', NEAR_TO))
const mitoticTo = Math.max(nearTo + 1, numParam(job.params, 'mitoticTo', MITOTIC_TO))
// The one thing that makes this measurement meaningless without saying so: the
// paper's bands are mouse-sized, and on an assembly whose longest sequence is
// shorter than the mitotic band's floor every cell scores exactly zero there —
// which draws as a column of points on the axis and reads as a result.
if (longest <= nearTo) {
job.note(
`The longest sequence here is ${Math.round(longest).toLocaleString()} bp, which is inside ` +
'the near band — so the mitotic and far bands are empty by construction and the phasing ' +
'plot says nothing. Set the band edges to this assembly’s own scale.',
)
}
const totals: CellTotals[] = names.map(() => ({
contacts: 0,
nnz: 0,
cis: 0,
trans: 0,
short: 0,
near: 0,
mitotic: 0,
far: 0,
}))
job.progress(0, names.length, 'reading cells')
await mc.scanCells({
onCell: (index, name) => job.progress(index, names.length, name),
onChunk: (cell, chunk) => {
job.throwIfCancelled()
const into = totals[cell]
for (let i = 0; i < chunk.length; i++) {
const bin1 = chunk.bin1[i]
const bin2 = chunk.bin2[i]
const raw = chunk.count[i]
const value = weights === null ? raw : raw * weights[bin1] * weights[bin2]
if (!Number.isFinite(value)) continue
into.nnz++
into.contacts += value
const c1 = contigOf[bin1]
const c2 = contigOf[bin2]
if (c1 < 0 || c2 < 0) continue
if (c1 !== c2) {
into.trans += value
continue
}
into.cis += value
// The separation of the **bins**, in base pairs. A contact inside one
// bin has a separation of zero, which lands in the short band, and that
// is the right home for it: a self-ligation and an unligated end are
// exactly what the short band is there to hold apart from structure.
const separation = Math.abs(bin2 - bin1) * mc.binsize
if (separation < nearFrom) into.short += value
else if (separation < nearTo) into.near += value
else if (separation < mitoticTo) into.mitotic += value
else into.far += value
}
return true
},
onProgress: () => job.throwIfCancelled(),
})
job.progress(names.length, names.length, 'done')
job.throwIfCancelled()
const tickedSet = new Set(ticked)
const share = (part: number, whole: number): number => (whole > 0 ? part / whole : Number.NaN)
const rows = names.map((name, i) => {
const cell = totals[i]
return {
cell: name,
ticked: tickedSet.has(name) ? 'yes' : '',
contacts: cell.contacts,
nnz: cell.nnz,
cis: share(cell.cis, cell.contacts),
trans: share(cell.trans, cell.contacts),
short: share(cell.short, cell.contacts),
near: share(cell.near, cell.contacts),
mitotic: share(cell.mitotic, cell.contacts),
far: share(cell.far, cell.contacts),
}
})
const empty = rows.filter((row) => row.contacts === 0).length
if (empty > 0) {
job.note(
`${empty.toLocaleString()} cell${empty === 1 ? ' has' : 's have'} no contact at all, so ` +
`${empty === 1 ? 'its' : 'their'} fractions are blank rather than zero.`,
)
}
const outputs: TaskOutput[] = [
{
kind: 'table',
id: 'cellqc',
label: `${names.length.toLocaleString()} cells`,
columns: [
{ key: 'cell', label: 'Cell', kind: 'text' },
{ key: 'ticked', label: 'Ticked', kind: 'text', hint: 'Whether this cell is in the set the map is drawn from.' },
{ key: 'contacts', label: 'Contacts', kind: 'number', digits: 0 },
{ key: 'nnz', label: 'Stored pixels', kind: 'number', digits: 0 },
{ key: 'cis', label: 'Cis', kind: 'number', digits: 3 },
{ key: 'trans', label: 'Trans', kind: 'number', digits: 3 },
{
key: 'short',
label: `< ${short(nearFrom)}`,
kind: 'number',
digits: 3,
hint: 'Self-ligation and unligated ends, mostly.',
},
{
key: 'near',
label: `${short(nearFrom)}–${short(nearTo)}`,
kind: 'number',
digits: 3,
hint: 'The near band. High in G1, low just after mitosis.',
},
{
key: 'mitotic',
label: `${short(nearTo)}–${short(mitoticTo)}`,
kind: 'number',
digits: 3,
hint: 'The mitotic band. The condensed chromosome’s signature.',
},
{ key: 'far', label: `> ${short(mitoticTo)}`, kind: 'number', digits: 3 },
],
rows,
} satisfies TableOutput,
]
const x = Float64Array.from(rows, (row) => row.near)
const y = Float64Array.from(rows, (row) => row.mitotic)
outputs.push({
kind: 'curve',
id: 'cellqc-phase',
label: 'Cell-cycle phasing',
series: [
{
name: `${names.length.toLocaleString()} cells`,
x,
y,
n: names.length,
// Points, because the cells have no order along x and a line through
// them would draw a path nothing travelled.
mark: 'points',
},
],
xLabel: `Contacts ${short(nearFrom)}–${short(nearTo)} (near)`,
yLabel: `Contacts ${short(nearTo)}–${short(mitoticTo)} (mitotic)`,
xScale: 'linear',
yScale: 'linear',
} satisfies CurveOutput)
return outputs
}
/** `2 Mb`, `23 kb` — a band edge short enough to be a column heading. */
function short(bp: number): string {
if (bp >= 1e6) return `${Number((bp / 1e6).toFixed(1))} Mb`
if (bp >= 1e3) return `${Number((bp / 1e3).toFixed(1))} kb`
return `${Math.round(bp)} bp`
}
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