liver mrd

Is disease still present after the resection?
512 draws (Python, shipped) · recomputed in 87 ms
headline

Informative molecules from tumour transrenal

0.00512 (2.1e-4–0.0721) informative molecules of tumour transrenal reach the detector, against 10,000 needed.

  • Detection at the operating tumour fraction of 0.1%, tumour-informed aggregate readout: 50.1% (50%–50.3%).
  • Limit of detection at 95%: ∞ (∞–∞).
  • Feasibility ratio, achieved over required molecules: 5.1e-7 (2.1e-8–7.2e-6).
  • 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 transrenal0.00512 (2.1e-4–0.0721)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

3,725 genome equivalents of tumour transrenal shed a day become 0.00512 informative in the tube: 5.9 decades lost, the steepest drop at M2 past the sieve, which keeps 0.189%.

under 60 bp60–100 bp100–170 bp170–300 bp300 bp and longer1e-40.01110010,000genome equivalents of the target source, log scale60–100 bp: 225 GE at M0 to 7.42 GE at M1100–170 bp: 1,672 GE at M0 to 55 GE at M1170–300 bp: 1,654 GE at M0 to 54.4 GE at M1300 bp and longer: 170 GE at M0 to 5.59 GE at M1−96.7%dilution: 50 mL of the day's urinekept 3.25% (1.85%–5.95%)under 60 bp: 0.128 GE at M1 to 0.0171 GE at M260–100 bp: 7.42 GE at M1 to 0.113 GE at M2100–170 bp: 55 GE at M1 to 0.0877 GE at M2170–300 bp: 54.4 GE at M1 to 0.0112 GE at M2300 bp and longer: 5.59 GE at M1 to 1.5e-4 GE at M2−99.8%the renal sieve on length and chromatinkept 0.189% (0.0203%–1.3%)under 60 bp: 0.0171 GE at M2 to 0.0821 GE at M360–100 bp: 0.113 GE at M2 to 0.107 GE at M3100–170 bp: 0.0877 GE at M2 to 0.0378 GE at M3170–300 bp: 0.0112 GE at M2 to 0.00197 GE at M3−<0.01%the nuclease: the leak below the gridkept 100% (100%–100%)under 60 bp: 0.0821 GE at M3 to 0.029 GE at M460–100 bp: 0.107 GE at M3 to 0.0559 GE at M4100–170 bp: 0.0378 GE at M3 to 0.0234 GE at M4170–300 bp: 0.00197 GE at M3 to 0.00132 GE at M4−49.5%void capture and the kit's recoverykept 50.5% (19.5%–115%)under 60 bp: 0.029 GE at M4 to 2.5e-4 GE at M560–100 bp: 0.0559 GE at M4 to 0.00205 GE at M5100–170 bp: 0.0234 GE at M4 to 0.00261 GE at M5170–300 bp: 0.00132 GE at M4 to 2.0e-4 GE at M5−95.3%library conversion and the footprint gatekept 4.72% (1.98%–9.92%)M0 shed3,725 GE a dayM0 shed · 60–100 bp: 6.05%, 225 GE a dayM0 shed · 100–170 bp: 44.9%, 1,672 GE a dayM0 shed · 170–300 bp: 44.4%, 1,654 GE a dayM0 shed · 300 bp and longer: 4.56%, 170 GE a dayM1 in the collected urine123 GEM1 in the collected urine · 60–100 bp: 6.05%, 7.42 GEM1 in the collected urine · 100–170 bp: 44.9%, 55 GEM1 in the collected urine · 170–300 bp: 44.4%, 54.4 GEM1 in the collected urine · 300 bp and longer: 4.56%, 5.59 GEM2 past the sieve0.229 GEM2 past the sieve · under 60 bp: 7.48%, 0.0171 GEM2 past the sieve · 60–100 bp: 49.2%, 0.113 GEM2 past the sieve · 100–170 bp: 38.3%, 0.0877 GEM2 past the sieve · 170–300 bp: 4.91%, 0.0112 GEM3 after the nuclease0.229 GEM3 after the nuclease · under 60 bp: 35.9%, 0.0821 GEM3 after the nuclease · 60–100 bp: 46.8%, 0.107 GEM3 after the nuclease · 100–170 bp: 16.5%, 0.0378 GEM3 after the nuclease · 170–300 bp: 0.86%, 0.00197 GEM4 collected and extracted0.11 GEM4 collected and extracted · under 60 bp: 26.5%, 0.029 GEM4 collected and extracted · 60–100 bp: 51%, 0.0559 GEM4 collected and extracted · 100–170 bp: 21.3%, 0.0234 GEM4 collected and extracted · 170–300 bp: 1.21%, 0.00132 GEM5 informative0.00512 GEM5 informative · under 60 bp: 4.82%, 2.5e-4 GEM5 informative · 60–100 bp: 40.2%, 0.00205 GEM5 informative · 100–170 bp: 51%, 0.00261 GEM5 informative · 170–300 bp: 3.97%, 2.0e-4 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: 45% shorter than 100 bp, 51% between 100 and 170 bp, 4% longer.
  • The neck against the requirement: 0.00512 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 readout (100% unreachable)single-locus counting (100% unreachable)operating pointshare of draws12510limit 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 transrenal go

The largest single loss at the medians is M2 past the sieve, which removes 99.8% of what reaches it.

M1 shed and diluted2.45 (1.11–5.37)M2 past the sieve0.00458 (3.9e-4–0.0368)M3 after the nuclease0.00458 (3.9e-4–0.0368)M4 collected and extracted0.00219 (1.4e-4–0.0213)M5 informative (post-footprint)1.0e-4 (4.2e-6–0.00144)1e-51e-40.0010.010.11genome 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: 6.91 (2.33–22.3) 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 mL50.1%
50%–50.2%
0.00324 mol.		50%
50%–50.2%
0.00234 mol.		50%
50%–50.2%
0.00149 mol.		50%
50%–50.1%
4.7e-4 mol.
25 mL50.1%
50%–50.3%
0.00491 mol.		50.1%
50%–50.2%
0.00347 mol.		50%
50%–50.2%
0.00222 mol.		50%
50%–50.1%
7.3e-4 mol.
50 mL50.1%
50%–50.3%
0.00744 mol.		50.1%
50%–50.3%
0.00512 mol.		50.1%
50%–50.2%
0.00323 mol.		50%
50%–50.2%
0.001 mol.
100 mL50.1%
50%–50.3%
0.0105 mol.		50.1%
50%–50.3%
0.00733 mol.		50.1%
50%–50.3%
0.00474 mol.		50%
50%–50.2%
0.00153 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.