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* The replication origin and terminus of each sequence, as a descriptor.
*
* The first step of every analysis of a bacterial chromosome's folding, and one
* that had to be done elsewhere: the map is read *from* the origin — its arms
* are aligned about it, its secondary diagonal crosses the main one there, and a
* figure puts it in the middle — so a reader needs to know where it is before
* the map means anything. Nothing in a `.cool` says, and most assemblies only
* happen to start near it.
*
* The sequence says, and `analysis/oriter.ts` reads it: the turning points of
* the cumulative GC skew are the two candidates, and which is the terminus is
* decided by the sites that mark each end — matS round the terminus of the
* enterobacteria, parS round the origin of most other bacteria — and, failing
* both, by the Hi-C coverage, which is highest where the chromosome was copied
* first. The motifs are parameters and default to the published consensuses:
* parS `TGTTNCACGTGNAACA` (Livny, Yamaichi & Waldor 2007), searched allowing
* one mismatch because each genome carries variants of it, and matS
* `GTGACRNYGTCAC` (Mercier et al. 2008), searched exactly because at one
* mismatch it turns up dozens of times by chance in a genome with no MatP.
*
* What it makes is **loci**: an `ori` and a `ter` per sequence, and the parS and
* matS sites they were placed against, as interval sets that draw on the map and
* leave as BED. The origin it finds is also the one the rest of the app reads
* the arms from (§8.15): the declaration is filled in on the Chromosomes table
* for every sequence the reader has not already given one.
*/
import { compileMotif, isMotifRefusal } from '../../annotations/motif'
import { tickedContigs } from '../context'
import type { AnalysisTask, CostEstimate, Params, ParamSpec, TableOutput, TaskOutput } from '../types'
import { READY, waitingFor } from '../types'
/** parS, the ParB binding site: the bacterial consensus of Livny, Yamaichi & Waldor (2007). */
export const PARS_CONSENSUS = 'TGTTNCACGTGNAACA'
/** matS, the MatP binding site, as Mercier et al. (2008) give it. */
export const MATS_CONSENSUS = 'GTGACRNYGTCAC'
const PARAMS: readonly ParamSpec[] = [
{
kind: 'sequence',
key: 'sequence',
label: 'reference',
hint: 'The FASTA to read the skew and the sites from.',
},
{ kind: 'sequences', key: 'sequences', label: 'sequences' },
{
kind: 'track',
key: 'coverage',
label: 'coverage',
optional: true,
noneLabel: 'Do not use coverage',
hint: 'Raw Hi-C coverage: breaks a tie, and gives the ori/ter ratio.',
startsEmpty: true,
},
{
kind: 'number',
key: 'window',
label: 'skew window',
unit: 'bp',
default: 5000,
min: 100,
integer: true,
section: 'GC skew',
},
{
kind: 'number',
key: 'step',
label: 'skew step',
unit: 'bp',
default: 1000,
min: 10,
integer: true,
section: 'GC skew',
},
{
kind: 'text',
key: 'parS',
label: 'parS motif',
default: PARS_CONSENSUS,
placeholder: PARS_CONSENSUS,
hint: 'Sites cluster round the origin; empty skips them.',
section: 'Sites',
},
{
kind: 'number',
key: 'parSMismatches',
label: 'parS mismatches',
default: 1,
min: 0,
max: 4,
integer: true,
section: 'Sites',
},
{
kind: 'text',
key: 'matS',
label: 'matS motif',
default: MATS_CONSENSUS,
placeholder: MATS_CONSENSUS,
hint: 'Ten or more sites place the terminus; empty skips them.',
section: 'Sites',
},
{
kind: 'number',
key: 'matSMismatches',
label: 'matS mismatches',
default: 0,
min: 0,
max: 4,
integer: true,
section: 'Sites',
},
{
kind: 'number',
key: 'knots',
label: 'spline knots',
hint: 'Of the cubic spline the coverage is smoothed with.',
default: 10,
min: 4,
max: 40,
integer: true,
section: 'Coverage',
when: (params) => typeof params.coverage === 'string' && params.coverage !== '',
},
]
/**
* The pattern a text parameter holds, cleaned the way the motif task cleans one.
*
* **Unanswered is the consensus and empty is none** — two answers, kept apart
* the way `sequences` keeps its two (§18.2): a job that never met a form, or a
* session written before a motif was a parameter, searches the published site,
* while a reader who cleared the box asked for that step to be skipped.
*/
export function sitePattern(params: Params, key: 'parS' | 'matS'): string {
const value = params[key]
if (value === undefined || value === null) return key === 'parS' ? PARS_CONSENSUS : MATS_CONSENSUS
return typeof value === 'string' ? value.replace(/\s+/g, '').toUpperCase() : ''
}
function estimate(context: Parameters<AnalysisTask['estimate']>[0], params: Params): CostEstimate {
const free = { class: 'free' as const, requests: 0, bytes: 0, note: 'Nothing to read.' }
const entry = params.sequence
if (typeof entry !== 'string' || entry === '') {
return {
...free,
refusal: 'Choose a reference. A FASTA dropped on the Annotations panel is one.',
}
}
for (const key of ['parS', 'matS'] as const) {
const pattern = sitePattern(params, key)
if (pattern === '') continue
const compiled = compileMotif(pattern)
if (isMotifRefusal(compiled)) return { ...free, refusal: `${key}: ${compiled.reason}` }
}
const chosen = context.hasMap ? tickedContigs(context, params, 'sequences') : context.contigs
if (context.hasMap && chosen.length === 0) {
return { ...free, refusal: 'Tick at least one sequence.' }
}
const bases = chosen.reduce((sum, contig) => sum + contig.length, 0)
const coverage = typeof params.coverage === 'string' && params.coverage !== ''
return {
class: 'free',
requests: 0,
bytes: 0,
note:
`One pass over ${(bases / 1e6).toFixed(1)} Mb of residues for the skew and the two motifs` +
`${coverage ? ', and the coverage track sampled at 5 kb' : ''}`,
}
}
export const ORITER_TASK: AnalysisTask = {
id: 'oriter',
title: 'Origin and terminus',
blurb: 'Where replication starts and ends, from the GC skew, parS, matS and coverage.',
keywords: ['ori', 'ter', 'replication', 'GC skew', 'dif'],
group: '1d',
// The residues are there and nowhere else; the coverage is a track, which is
// there too.
venue: 'annotations',
version: 1,
availability: (context) =>
context.entries.some((entry) => entry.kind === 'sequence')
? READY
: waitingFor('Load the FASTA of the genome.'),
params: PARAMS,
outputs: ['intervals', 'table', 'profile'],
estimate,
}
/**
* The origins a run placed, 0-based, by sequence — what the session declares.
*
* Read from the table's `ori`, which is where the call put it, and not from the
* `ori` locus: that is a window wide and cut at the sequence's ends, so near
* the first base — where most assemblies of a bacterial chromosome start — its
* middle is up to half a window from the origin it was drawn round.
*/
export function declaredOrigins(outputs: readonly TaskOutput[]): Record<string, number> {
const table = outputs.find(
(output): output is TableOutput => output.kind === 'table' && output.id === 'oriter-table',
)
const found: Record<string, number> = {}
for (const row of table?.rows ?? []) {
const at = Number(row.ori)
if (typeof row.sequence === 'string' && Number.isFinite(at) && at >= 1) {
found[row.sequence] = Math.floor(at) - 1
}
}
return found
}
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