upper tract

Does this patient have a tumour now?
512 draws (Python, shipped) · recomputed in 370 ms
headline

Informative molecules from tumour luminal

9,671 (1,414–46,437) informative molecules of tumour luminal reach the detector, against 3,000 needed.

  • Detection at the operating tumour fraction of 1%, tumour-informed aggregate readout: 100% (100%–100%).
  • Limit of detection at 95%: 0.034% (0.011%–0.167%).
  • Feasibility ratio, achieved over required molecules: 3.22 (0.471–15.5).
  • The 5% quantile of detection clears the 90% target, so this design is viable under the priors.
requiredurothelium6,815 (1,143–26,605)renal tubule676 (113–2,638)leukocyte0.072 (0.00346–1.06)hepatocyte0.0313 (0.00148–0.452)tumour luminal9,671 (1,414–46,437)tumour transrenal0.102 (0.0042–1.44)0.0010.010.11101001,00010,000informative molecules in the tube (GE)
Median, 25–75% box and 5–95% whisker over 512 draws. The target source is drawn solid.
funnel

From shedding to the detector

8.1e6 genome equivalents of tumour luminal shed a day become 9,671 informative in the tube: 2.9 decades lost, the steepest drop at M1 in the collected urine, which keeps 3.25%.

under 60 bp60–100 bp100–170 bp170–300 bp300 bp and longer1,0001e51e7genome equivalents of the target source, log scaleunder 60 bp: 1.0e6 GE at M0 to 31,441 GE at M160–100 bp: 2.0e6 GE at M0 to 61,852 GE at M1100–170 bp: 2.6e6 GE at M0 to 81,118 GE at M1170–300 bp: 1.8e6 GE at M0 to 55,845 GE at M1300 bp and longer: 6.4e5 GE at M0 to 19,797 GE at M1−96.7%dilution: 50 mL of the day's urinekept 3.25% (1.85%–5.95%)under 60 bp: 31,441 GE at M1 to 31,441 GE at M260–100 bp: 61,852 GE at M1 to 61,852 GE at M2100–170 bp: 81,118 GE at M1 to 81,118 GE at M2170–300 bp: 55,845 GE at M1 to 55,845 GE at M2300 bp and longer: 19,797 GE at M1 to 19,797 GE at M20%no sieve on the luminal routekept 100% (100%–100%)under 60 bp: 31,441 GE at M2 to 95,122 GE at M360–100 bp: 61,852 GE at M2 to 88,524 GE at M3100–170 bp: 81,118 GE at M2 to 52,177 GE at M3170–300 bp: 55,845 GE at M2 to 13,016 GE at M3300 bp and longer: 19,797 GE at M2 to 1,213 GE at M3−<0.01%the nuclease: the leak below the gridkept 100% (100%–100%)under 60 bp: 95,122 GE at M3 to 34,675 GE at M460–100 bp: 88,524 GE at M3 to 49,079 GE at M4100–170 bp: 52,177 GE at M3 to 35,149 GE at M4170–300 bp: 13,016 GE at M3 to 9,599 GE at M4300 bp and longer: 1,213 GE at M3 to 921 GE at M4−48.1%void capture and the kit's recoverykept 51.9% (19.5%–116%)under 60 bp: 34,675 GE at M4 to 319 GE at M560–100 bp: 49,079 GE at M4 to 2,124 GE at M5100–170 bp: 35,149 GE at M4 to 4,705 GE at M5170–300 bp: 9,599 GE at M4 to 2,237 GE at M5300 bp and longer: 921 GE at M4 to 285 GE at M5−92.9%library conversion and the footprint gatekept 7.12% (2.47%–14.9%)M0 shed8.1e6 GE a dayM0 shed · under 60 bp: 12.6%, 1.0e6 GE a dayM0 shed · 60–100 bp: 24.7%, 2.0e6 GE a dayM0 shed · 100–170 bp: 32.4%, 2.6e6 GE a dayM0 shed · 170–300 bp: 22.3%, 1.8e6 GE a dayM0 shed · 300 bp and longer: 7.92%, 6.4e5 GE a dayM1 in the collected urine2.5e5 GEM1 in the collected urine · under 60 bp: 12.6%, 31,441 GEM1 in the collected urine · 60–100 bp: 24.7%, 61,852 GEM1 in the collected urine · 100–170 bp: 32.4%, 81,118 GEM1 in the collected urine · 170–300 bp: 22.3%, 55,845 GEM1 in the collected urine · 300 bp and longer: 7.92%, 19,797 GEM2 past the sieve2.5e5 GEM2 past the sieve · under 60 bp: 12.6%, 31,441 GEM2 past the sieve · 60–100 bp: 24.7%, 61,852 GEM2 past the sieve · 100–170 bp: 32.4%, 81,118 GEM2 past the sieve · 170–300 bp: 22.3%, 55,845 GEM2 past the sieve · 300 bp and longer: 7.92%, 19,797 GEM3 after the nuclease2.5e5 GEM3 after the nuclease · under 60 bp: 38%, 95,122 GEM3 after the nuclease · 60–100 bp: 35.4%, 88,524 GEM3 after the nuclease · 100–170 bp: 20.9%, 52,177 GEM3 after the nuclease · 170–300 bp: 5.21%, 13,016 GEM3 after the nuclease · 300 bp and longer: 0.485%, 1,213 GEM4 collected and extracted1.3e5 GEM4 collected and extracted · under 60 bp: 26.8%, 34,675 GEM4 collected and extracted · 60–100 bp: 37.9%, 49,079 GEM4 collected and extracted · 100–170 bp: 27.2%, 35,149 GEM4 collected and extracted · 170–300 bp: 7.42%, 9,599 GEM4 collected and extracted · 300 bp and longer: 0.712%, 921 GEM5 informative9,671 GEM5 informative · under 60 bp: 3.3%, 319 GEM5 informative · 60–100 bp: 22%, 2,124 GEM5 informative · 100–170 bp: 48.7%, 4,705 GEM5 informative · 170–300 bp: 23.1%, 2,237 GEM5 informative · 300 bp and longer: 2.95%, 285 GErequired 3,000
Each stop is the median over draws of the target source's genome equivalents, its width on a log scale, so equal tapers are equal factors wherever they happen. The whisker at each stop is the 5–95% spread. The ribbons carry the length classes through; the grey behind them is what the stage removed. Hover a ribbon or a stop for its numbers.
  • What gets through at M5: 25.3% shorter than 100 bp, 48.7% between 100 and 170 bp, 26.1% longer.
  • The neck against the requirement: 9,671 informative against 3,000 needed, the neck clears it at the median.
detection

Detection probability against tumour fraction

The curve says where the assay starts to work; the band says how sure the priors are of it.

00.20.40.60.81tumour-informed aggregate readout (median, 5–95%)single-locus counting (median, 5–95%)operating pointprobability of detection1e-43e-40.0010.0030.010.030.10.3tumour fraction
Median with the 5–95% band over draws, at the current collection and assay.
00.250.50.751tumour-informed aggregate readoutsingle-locus countingoperating pointshare of draws3e-51e-43e-40.0010.0030.010.03limit of detection at 95% (tumour fraction)
Cumulative share of draws whose 95% limit of detection lies below each tumour fraction. Draws that never reach 95% are counted as unreachable.
cascade

Where the molecules of tumour luminal go

The largest single loss at the medians is M5 informative (post-footprint), which removes 92.5% of what reaches it.

M1 shed and diluted5,001 (2,055–13,968)M2 past the sieve5,001 (2,055–13,968)M3 after the nuclease5,001 (2,054–13,967)M4 collected and extracted2,588 (655–11,371)M5 informative (post-footprint)193 (28.3–929)301003001,0003,00010,000genome equivalents per mL of urine
Each stage's total for the target source, in GE/mL. M3 only redistributes mass over length, so its loss is the sub-detectable leak; the footprint gate at M5 is where a long amplicon costs the most.
  • Extracted DNA yield, all sources: 16 (4.9–56.4) ng/mL.
  • Median fragment length of the extracted population: 65 (50–80) bp.
length

What the nuclease and the footprint leave

The population after M3 sits far below the footprint for most of its molecules; the informative population is the tail the assay can still read.

00.020.040.060.080.1after the nuclease (M3) (median, 5–95%)informative (M5) (median, 5–95%)footprintshare of molecules per bin2004006008001,000fragment length (bp)
Weighted mean over draws of each draw's normalised molecule-count profile for the target source.
design

Collected volume against assay footprint

Each cell replays the same draws through one design; the comparison is between designs, not between samplings.

volume \ footprint30 bp45 bp60 bp90 bp
10 mL100%
99.7%–100%
5,143 mol.		100%
98.7%–100%
3,954 mol.		100%
96%–100%
2,982 mol.		100%
84%–100%
1,618 mol.
25 mL100%
100%–100%
8,558 mol.		100%
99.9%–100%
6,602 mol.		100%
99.3%–100%
4,967 mol.		100%
91.7%–100%
2,691 mol.
50 mL100%
100%–100%
12,703 mol.		100%
100%–100%
9,671 mol.		100%
99.9%–100%
7,312 mol.		100%
94.9%–100%
4,004 mol.
100 mL100%
100%–100%
17,679 mol.		100%
100%–100%
13,597 mol.		100%
100%–100%
10,346 mol.		100%
98.1%–100%
5,555 mol.

Detection at the operating point: median, 5–95% range, and the median informative molecules. Green clears the target at the 5% quantile, amber clears it only at the median, red has too few molecules for the assay class. The current design is outlined. Every other control applies to every cell.

method

How this page computes

  • The chain M0 to M6 runs in this page in JavaScript, checked against the Python model on fixed draws to a relative 1e-8 on every stage and readout.
  • The 512 shipped draws are Python's, seeds 0 to 511, with their post-nuclease states solved at build time. Volume, kit, footprint, chemistry, platform, tumour volume, injury and urine output are downstream or linear, so they recompute in the page.
  • Hold, temperature, preservative, pH, filtration and proteinuria change the nuclease input, so the page re-solves the fragmentation master equation for every draw in a pool of workers, by the action of the matrix exponential on each draw's own profiles.
  • A prior edit reweights the draws by the ratio of the new density to the old, which is exact but thins the sample; the effective sample size says by how much. Fresh draws sample the edited priors in the page and re-solve.