04 · 21 proprietary layers
Layer 2 of 21 · Six shared core layers
SourceGuard Somatic and germline interpretation.
Why it's needed
Is a finding interpreted as tumour-acquired, potentially inherited, or unresolved in the context of available samples and workflow?
What it draws on
2 of 8 evidence domains.
What it produces
Classification or context of findings, and items that may need confirmation or clinical genetics review.
Why it's essential
Layer 2 of 21.
1 · What it does
What SourceGuard does
Not every variant found in tumour DNA was acquired by the tumour. Some are inherited and present in every cell of the body. SourceGuard is intended to flag whether a finding looks tumour-acquired (somatic), potentially inherited (germline) or unresolved, because each needs a different interpretation framework and has different implications.
2 · Scientific question
The question it addresses
Is a finding interpreted as tumour-acquired, potentially inherited, or unresolved in the context of available samples and workflow?
Intended function
Explain how tumour and germline context may be distinguished or flagged.
3 · Data inputs and required context
What it draws on
- 01 Molecular & genomic
- 07 Patient factors
Tumour and, where the pathway includes it, germline data. Twin Liquid includes hereditary testing for germline filtering.
4 · Scientific basis
The science behind it
Scientific basis
With a matched normal sample, somatic and germline variants can be separated by direct comparison. In tumour-only testing, origin is inferred from allele fraction, population-frequency data and known patterns, and that inference can be wrong in either direction. In plasma, variants from clonal haematopoiesis (age-related changes in blood cells) can resemble tumour variants.
5 · Output and evidence sources
What it produces
Main output
Classification or context of findings, and items that may need confirmation or clinical genetics review.
Output type
- Computational inference. Estimated by analysis of available data rather than measured directly.
- Assay-derived finding. Reported from laboratory sequencing data, subject to assay scope and quality.
6 · Why it\u2019s essential
How it powers the Twin
Decides which interpretation framework applies downstream: germline pathogenicity or somatic oncogenicity and actionability. Possible inherited findings are routed for confirmation and genetic counselling rather than reported as tumour findings.
Report section
7 · Why it\u2019s needed
What it changes — for doctors, patients and researchers
Clinicians
Flags findings that may warrant confirmatory germline testing and referral for genetic counselling.
Doctor & Clinical TeamPatients & caregivers
A possibly inherited finding can matter for relatives as well as the patient. It needs counselling, consent and confirmation before it is treated as a diagnosis.
Patient & CaregiverResearchers
Correct origin assignment keeps germline variation out of somatic analyses.
Industry & Research8 · Dependencies and limitations
Limitations
- Clonal haematopoiesis can produce plasma variants that are neither tumour-derived nor inherited.
9 · Review and uncertainty
How the output is handled
Output status
An AI-assisted analytical output presented as structured findings for clinician review. It becomes part of a report only after the treating oncologist has reviewed and signed it.
How uncertainty is communicated
Findings are labelled as likely somatic, possibly germline (confirmation advised) or unresolved, rather than forced into a single category.
10 · Claim boundary
What this layer does not establish
A 'possibly germline' flag is not a hereditary diagnosis. Confirmatory germline testing with appropriate consent and counselling is required.
The treating oncologist owns every decision. Every Twin report is reviewed and signed by the treating oncologist, then taken to KPCIRC's Molecular Tumour Board.
KPCIRC sign-off process