bladder surveillance

Is disease still present after the resection?
512 draws (Python, shipped) · recomputed in 287 ms
headline

Informative molecules from tumour luminal

5,373 (786–25,798) informative molecules of tumour luminal reach the detector, against 10,000 needed.

  • Detection at the operating tumour fraction of 0.1%, tumour-informed aggregate readout: 99.2% (82%–100%).
  • Limit of detection at 95%: 0.0531% (0.0157%–0.289%).
  • Feasibility ratio, achieved over required molecules: 0.537 (0.0786–2.58).
  • The median draw carries fewer informative molecules than the assay class needs (10,000), so this is an architectural failure: no optimisation of depth fixes it.
requiredurothelium6,815 (1,143–26,605)renal tubule676 (113–2,638)leukocyte0.072 (0.00346–1.06)hepatocyte0.0313 (0.00148–0.452)tumour luminal5,373 (786–25,798)tumour transrenal0.0512 (0.0021–0.721)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

4.5e6 genome equivalents of tumour luminal shed a day become 5,373 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: 5.6e5 GE at M0 to 17,467 GE at M160–100 bp: 1.1e6 GE at M0 to 34,362 GE at M1100–170 bp: 1.5e6 GE at M0 to 45,066 GE at M1170–300 bp: 1.0e6 GE at M0 to 31,025 GE at M1300 bp and longer: 3.5e5 GE at M0 to 10,998 GE at M1−96.7%dilution: 50 mL of the day's urinekept 3.25% (1.85%–5.95%)under 60 bp: 17,467 GE at M1 to 17,467 GE at M260–100 bp: 34,362 GE at M1 to 34,362 GE at M2100–170 bp: 45,066 GE at M1 to 45,066 GE at M2170–300 bp: 31,025 GE at M1 to 31,025 GE at M2300 bp and longer: 10,998 GE at M1 to 10,998 GE at M20%no sieve on the luminal routekept 100% (100%–100%)under 60 bp: 17,467 GE at M2 to 52,846 GE at M360–100 bp: 34,362 GE at M2 to 49,180 GE at M3100–170 bp: 45,066 GE at M2 to 28,987 GE at M3170–300 bp: 31,025 GE at M2 to 7,231 GE at M3300 bp and longer: 10,998 GE at M2 to 674 GE at M3−<0.01%the nuclease: the leak below the gridkept 100% (100%–100%)under 60 bp: 52,846 GE at M3 to 19,264 GE at M460–100 bp: 49,180 GE at M3 to 27,266 GE at M4100–170 bp: 28,987 GE at M3 to 19,527 GE at M4170–300 bp: 7,231 GE at M3 to 5,333 GE at M4300 bp and longer: 674 GE at M3 to 512 GE at M4−48.1%void capture and the kit's recoverykept 51.9% (19.5%–116%)under 60 bp: 19,264 GE at M4 to 177 GE at M560–100 bp: 27,266 GE at M4 to 1,180 GE at M5100–170 bp: 19,527 GE at M4 to 2,614 GE at M5170–300 bp: 5,333 GE at M4 to 1,243 GE at M5300 bp and longer: 512 GE at M4 to 158 GE at M5−92.9%library conversion and the footprint gatekept 7.12% (2.47%–14.9%)M0 shed4.5e6 GE a dayM0 shed · under 60 bp: 12.6%, 5.6e5 GE a dayM0 shed · 60–100 bp: 24.7%, 1.1e6 GE a dayM0 shed · 100–170 bp: 32.4%, 1.5e6 GE a dayM0 shed · 170–300 bp: 22.3%, 1.0e6 GE a dayM0 shed · 300 bp and longer: 7.92%, 3.5e5 GE a dayM1 in the collected urine1.4e5 GEM1 in the collected urine · under 60 bp: 12.6%, 17,467 GEM1 in the collected urine · 60–100 bp: 24.7%, 34,362 GEM1 in the collected urine · 100–170 bp: 32.4%, 45,066 GEM1 in the collected urine · 170–300 bp: 22.3%, 31,025 GEM1 in the collected urine · 300 bp and longer: 7.92%, 10,998 GEM2 past the sieve1.4e5 GEM2 past the sieve · under 60 bp: 12.6%, 17,467 GEM2 past the sieve · 60–100 bp: 24.7%, 34,362 GEM2 past the sieve · 100–170 bp: 32.4%, 45,066 GEM2 past the sieve · 170–300 bp: 22.3%, 31,025 GEM2 past the sieve · 300 bp and longer: 7.92%, 10,998 GEM3 after the nuclease1.4e5 GEM3 after the nuclease · under 60 bp: 38%, 52,846 GEM3 after the nuclease · 60–100 bp: 35.4%, 49,180 GEM3 after the nuclease · 100–170 bp: 20.9%, 28,987 GEM3 after the nuclease · 170–300 bp: 5.21%, 7,231 GEM3 after the nuclease · 300 bp and longer: 0.485%, 674 GEM4 collected and extracted71,902 GEM4 collected and extracted · under 60 bp: 26.8%, 19,264 GEM4 collected and extracted · 60–100 bp: 37.9%, 27,266 GEM4 collected and extracted · 100–170 bp: 27.2%, 19,527 GEM4 collected and extracted · 170–300 bp: 7.42%, 5,333 GEM4 collected and extracted · 300 bp and longer: 0.712%, 512 GEM5 informative5,373 GEM5 informative · under 60 bp: 3.3%, 177 GEM5 informative · 60–100 bp: 22%, 1,180 GEM5 informative · 100–170 bp: 48.7%, 2,614 GEM5 informative · 170–300 bp: 23.1%, 1,243 GEM5 informative · 300 bp and longer: 2.95%, 158 GErequired 10,000
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: 5,373 informative against 10,000 needed, the neck does not reach 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 draws1e-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 diluted2,778 (1,141–7,760)M2 past the sieve2,778 (1,141–7,760)M3 after the nuclease2,778 (1,141–7,759)M4 collected and extracted1,438 (364–6,317)M5 informative (post-footprint)107 (15.7–516)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: 12.2 (3.74–40.4) 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 mL96.1%
72.3%–100%
2,857 mol.		93.8%
68.3%–100%
2,197 mol.		91%
64.3%–100%
1,657 mol.		83.9%
58.4%–99.9%
899 mol.
25 mL98.8%
80.8%–100%
4,755 mol.		97.7%
75.7%–100%
3,668 mol.		96%
69.7%–100%
2,759 mol.		90.1%
61.3%–100%
1,495 mol.
50 mL99.7%
86.4%–100%
7,057 mol.		99.2%
82%–100%
5,373 mol.		98.2%
74.7%–100%
4,062 mol.		93.6%
64%–100%
2,225 mol.
100 mL99.9%
91.7%–100%
9,822 mol.		99.8%
86.2%–100%
7,554 mol.		99.4%
79.9%–100%
5,748 mol.		96.7%
67.2%–100%
3,086 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.