METHODOLOGY COMPARED

 

Three ways to monitor ctDNA. They are not interchangeable.


Tumour-informed monitoring splits broadly into three approaches: tracking single nucleotide variants, tracking structural variants, or using fixed tumour-naive panels. Each has consequences for your samples. Most platforms hide this choice. We think it deserves daylight.

AT A GLANCE

 

The three approaches, in plain terms.


Each is a real, valid methodology. Each is the right answer for a different set of samples and a different clinical question.

———
SNV-based

 SIMSEN APPROACH

Personalised panel built from the patient's own tumour profile. Tracks single nucleotide variants at parts-per-million sensitivity, including actionable and resistance variants.

Best when: small biopsies, low tumour burden, you want resistance signal, paediatric and early-stage samples.

 

———
SV-based

  

Personalised panel built around structural variants identified in the tumour. Sensitive in tumour types with high SV burden. Does not return resistance information.

Best when: SV-rich tumours, resistance tracking not required, when SV breakpoints are well characterised.

 

———
Tumour-naive

  

Fixed panel covering common variants. No tumour tissue needed. Lower sensitivity at very low allele frequencies; misses patient-specific variants outside the fixed panel..

Best when: no tissue available, sensitivity is secondary, broad surveillance is acceptable.

 
SIDE BY SIDE

 

What each approach actually delivers, attribute by attribute.

Independent of vendor names. This is the underlying methodology comparison; specific products from any provider sit inside one of these three columns.

ATTRIBUTE SNV-based SiMSen approach SV-based Tumour-naive
Limit of detection (VAF) ✓ <0.001%
Single-molecule resolution with consensus depth.
 ✓ ~0.01%
SV breakpoints provide strong signal, where present.
 ~ 0.1-1%
Limited by fixed-panel background error.
Tumour-tissue required ✓ Yes
FFPE block or fresh sample, once, for panel design.
 ✓ Yes
For SV characterisation.
 – No
Fixed panel, no biopsy needed.
Actionable / resistance variants ✓ Yes
Personalised panel surfaces clinically actionable and resistance variants.
 – No
SV breakpoints carry no resistance information.
 – Limited
Only variants on the fixed panel are returned.
Performance in small biopsies / low input ✓ Strong
10-50 ng cfDNA input. Validated on paediatric and surgical samples.
 ~ Variable
Depends on SV burden in the tumour type.
 – Weaker
Lower sensitivity makes low-input cases marginal.
Longitudinal monitoring ✓ Yes
Same personalised panel reused across plasma points.
 ✓ Yes
Same SV panel reused.
 ✓ Yes
Fixed panel reused.
Panel design lead time ~ 2-3 weeks
From tumour sample receipt. One-off; subsequent plasma runs are standard turnaround.
 ~ 2-3 weeks
SV characterisation adds time.
 ✓ None
Off-the-shelf, no design step.
Cost per sample ~ Mid-high
Personalised design cost amortised across longitudinal samples.
 ~ Mid-high
Similar economics to SNV-based.
 ✓ Lower
Off-the-shelf, lower per-sample cost.
Raw data access ✓ Yes
FASTQ + BAM. Open pipeline. Bring your own bioinformatics in.
 ~ Vendor-dependent
Varies by provider.
 ~ Vendor-dependent
Often summary only.
CHOOSING WELL

 

When each approach is the right choice, including when ours is not.


We are tumour-informed SNV specialists, and we will say so when another method is a better fit for your samples. The clinical question, the sample type and the tissue availability decide the methodology, in that order.

CHOOSE SNV-BASED WHEN

Sensitivity is the constraint and tissue is available.

—Minimal residual disease monitoring after curative-intent treatment.
—Paediatric tumours, low-burden cases, small biopsies.
—You need actionable variants and resistance tracking, not just yes/no.
—Co-publication, raw data and pipeline transparency matter to you.

CHOOSE SV-BASED WHEN

The tumour type carries strong SV signal and resistance is not the question.

—SV-rich tumour types where breakpoints are well characterised.
—SV-rich tumour types where breakpoints are well characterised.
—SV-specific bioinformatics expertise is available in your team or your provider.

CHOOSE SNV-BASED WHEN

Sensitivity is the constraint and tissue is available.

—Minimal residual disease monitoring after curative-intent treatment.
—Paediatric tumours, low-burden cases, small biopsies.
—You need actionable variants and resistance tracking, not just yes/no.
—Co-publication, raw data and pipeline transparency matter to you.

DECISION GUIDE

Four questions to your best-fit methodology.

Answer four short questions about your samples, your tumour type and your clinical question. The guide returns the methodology that fits, with a transparent reason for the recommendation, even when it is not ours.
 
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A real human, in CET/CEST time zone, who has run samples like yours.