renal cell localised

Does this patient have a tumour now?
512 draws (Python, shipped) · recomputed in 336 ms
headline

Informative molecules from tumour luminal

7,199 (1,053–34,570) 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% (99.8%–100%).
  • Limit of detection at 95%: 0.062% (0.0179%–0.349%).
  • Feasibility ratio, achieved over required molecules: 2.4 (0.351–11.5).
  • 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 luminal7,199 (1,053–34,570)tumour transrenal1.71 (0.0704–24.2)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

6.0e6 genome equivalents of tumour luminal shed a day become 7,199 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: 7.5e5 GE at M0 to 23,406 GE at M160–100 bp: 1.5e6 GE at M0 to 46,045 GE at M1100–170 bp: 1.9e6 GE at M0 to 60,388 GE at M1170–300 bp: 1.3e6 GE at M0 to 41,574 GE at M1300 bp and longer: 4.8e5 GE at M0 to 14,737 GE at M1−96.7%dilution: 50 mL of the day's urinekept 3.25% (1.85%–5.95%)under 60 bp: 23,406 GE at M1 to 23,406 GE at M260–100 bp: 46,045 GE at M1 to 46,045 GE at M2100–170 bp: 60,388 GE at M1 to 60,388 GE at M2170–300 bp: 41,574 GE at M1 to 41,574 GE at M2300 bp and longer: 14,737 GE at M1 to 14,737 GE at M20%no sieve on the luminal routekept 100% (100%–100%)under 60 bp: 23,406 GE at M2 to 70,813 GE at M360–100 bp: 46,045 GE at M2 to 65,901 GE at M3100–170 bp: 60,388 GE at M2 to 38,843 GE at M3170–300 bp: 41,574 GE at M2 to 9,690 GE at M3300 bp and longer: 14,737 GE at M2 to 903 GE at M3−<0.01%the nuclease: the leak below the gridkept 100% (100%–100%)under 60 bp: 70,813 GE at M3 to 25,814 GE at M460–100 bp: 65,901 GE at M3 to 36,537 GE at M4100–170 bp: 38,843 GE at M3 to 26,166 GE at M4170–300 bp: 9,690 GE at M3 to 7,146 GE at M4300 bp and longer: 903 GE at M3 to 686 GE at M4−48.1%void capture and the kit's recoverykept 51.9% (19.5%–116%)under 60 bp: 25,814 GE at M4 to 238 GE at M560–100 bp: 36,537 GE at M4 to 1,581 GE at M5100–170 bp: 26,166 GE at M4 to 3,503 GE at M5170–300 bp: 7,146 GE at M4 to 1,665 GE at M5300 bp and longer: 686 GE at M4 to 212 GE at M5−92.9%library conversion and the footprint gatekept 7.12% (2.47%–14.9%)M0 shed6.0e6 GE a dayM0 shed · under 60 bp: 12.6%, 7.5e5 GE a dayM0 shed · 60–100 bp: 24.7%, 1.5e6 GE a dayM0 shed · 100–170 bp: 32.4%, 1.9e6 GE a dayM0 shed · 170–300 bp: 22.3%, 1.3e6 GE a dayM0 shed · 300 bp and longer: 7.92%, 4.8e5 GE a dayM1 in the collected urine1.9e5 GEM1 in the collected urine · under 60 bp: 12.6%, 23,406 GEM1 in the collected urine · 60–100 bp: 24.7%, 46,045 GEM1 in the collected urine · 100–170 bp: 32.4%, 60,388 GEM1 in the collected urine · 170–300 bp: 22.3%, 41,574 GEM1 in the collected urine · 300 bp and longer: 7.92%, 14,737 GEM2 past the sieve1.9e5 GEM2 past the sieve · under 60 bp: 12.6%, 23,406 GEM2 past the sieve · 60–100 bp: 24.7%, 46,045 GEM2 past the sieve · 100–170 bp: 32.4%, 60,388 GEM2 past the sieve · 170–300 bp: 22.3%, 41,574 GEM2 past the sieve · 300 bp and longer: 7.92%, 14,737 GEM3 after the nuclease1.9e5 GEM3 after the nuclease · under 60 bp: 38%, 70,813 GEM3 after the nuclease · 60–100 bp: 35.4%, 65,901 GEM3 after the nuclease · 100–170 bp: 20.9%, 38,843 GEM3 after the nuclease · 170–300 bp: 5.21%, 9,690 GEM3 after the nuclease · 300 bp and longer: 0.485%, 903 GEM4 collected and extracted96,348 GEM4 collected and extracted · under 60 bp: 26.8%, 25,814 GEM4 collected and extracted · 60–100 bp: 37.9%, 36,537 GEM4 collected and extracted · 100–170 bp: 27.2%, 26,166 GEM4 collected and extracted · 170–300 bp: 7.42%, 7,146 GEM4 collected and extracted · 300 bp and longer: 0.712%, 686 GEM5 informative7,199 GEM5 informative · under 60 bp: 3.3%, 238 GEM5 informative · 60–100 bp: 22%, 1,581 GEM5 informative · 100–170 bp: 48.7%, 3,503 GEM5 informative · 170–300 bp: 23.1%, 1,665 GEM5 informative · 300 bp and longer: 2.95%, 212 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: 7,199 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 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 diluted3,723 (1,530–10,398)M2 past the sieve3,723 (1,530–10,398)M3 after the nuclease3,723 (1,529–10,398)M4 collected and extracted1,927 (488–8,465)M5 informative (post-footprint)144 (21.1–691)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: 13.8 (4.29–46.9) 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%
97%–100%
3,829 mol.		100%
93.6%–100%
2,944 mol.		100%
88.3%–100%
2,220 mol.		99.9%
75.3%–100%
1,204 mol.
25 mL100%
99.7%–100%
6,371 mol.		100%
98.6%–100%
4,914 mol.		100%
95.5%–100%
3,698 mol.		100%
80.3%–100%
2,004 mol.
50 mL100%
100%–100%
9,457 mol.		100%
99.8%–100%
7,199 mol.		100%
98.4%–100%
5,444 mol.		100%
86.8%–100%
2,981 mol.
100 mL100%
100%–100%
13,161 mol.		100%
100%–100%
10,122 mol.		100%
99.5%–100%
7,702 mol.		100%
91.9%–100%
4,136 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.