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.

Simsen approach

SNV-based

Personalised and ultra-sensitive, surfacing clinically actionable variants alongside tumour markers.

Best when: small biopsies, low tumour burden, you want resistance signal.

SV-based

Personalised, sensitive in tumour types with high structural-variant burden, but no resistance information.

Best when: SV-rich tumours, resistance tracking not required.

Tumour-naive

Fixed panel, no biopsy needed, lower sensitivity at very low allele frequencies.

Best when: no tissue available, sensitivity is secondary.

Side by side

What each approach actually delivers, attribute by attribute.

Attribute	SNV-basedSimsen Approach	SV-based	Tumour-naive
Limit of detection (VAF)	~0.001% (panel-level) per-variant ~0.01%; aggregate across the ~20–30 variant panel ~0.001% 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 reuse
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 time
Cost per sample	Low-high Personalised design cost amortised across longitudinal samples. Many timepoints decrease cost per sample to lesser than tumour-naive panels.	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.
You want personalised tracking but resistance variants are not the clinical question.
SV-specific bioinformatics expertise is available in your team or your provider.

Choose tumour-naive when

No tissue, broad surveillance, or sensitivity is secondary.

No tumour tissue available for personalised panel design.
Population-level screening or broad surveillance use cases.
Sensitivity at low VAF is not the deciding factor for your question.
You need a faster, lower-cost per-sample option and can accept the trade-off.