A normalized model score used to rank which pathway signals deserve follow-up first.
It is not a measured enzyme percentage, metabolite concentration, diagnosis, or disease probability.
The evidence can strongly support whether a genotype points toward higher burden or lower capacity.
Symptoms, biomarkers, diet, medications, and clinical context decide whether the DNA signal is active now.
Plain rule
Use the score as a follow-up priority, not as a biological percentage
Safe wording
"This pathway has a strong DNA-based signal and should be checked with symptoms, biomarkers, and context."
Avoid this wording
"This pathway is reduced by 52%" or "this enzyme is 52% impaired." The report score is not a direct laboratory or enzyme measurement.
Method
How the model creates a pathway score
- Study evidence is curated first. Each study contributes direction, magnitude, and support for one genotype and one target.
- Studies are aggregated into a claim score. Same-direction evidence accumulates with diminishing returns; magnitude is weighted by study support.
- Claims become gene signals. The strongest matched evidence for that gene is used as the gene-level signal.
- Genes are placed into pathway topology blocks. Direct, serial, backup, and low-impact blocks decide how much each gene can change the pathway result.
- The pathway score ranks follow-up priority. Higher scores deserve more attention, but validation still decides whether the signal is active in real life.
Worked example
Lactose digestion score: why 0.519 can stay
In the sample report, the lactose digestion pathway is driven by the matched genotype rs4988235 GG, equivalent to the older -13910 C/C notation.
The science supports the direction: this genotype points toward lower adult lactase persistence. It does not prove current lactose intolerance.
This is the normalized follow-up score produced by the evidence and topology model. It should not be read as "52% lactase loss."
Calculation used for this sample
Aggregated evidence support0.951
Aggregated magnitude0.546
Claim score0.951 x 0.546 = 0.519
Topology handlingDirect LCT block
Because the lactose pathway is modeled as a direct adult LCT expression-capacity block, the claim score becomes the visible pathway score in this sample.
| Evidence | Direction | Magnitude | Support | Source |
|---|---|---|---|---|
| Enattah 2002Biochemically verified association Identified the C/T-13910 variant upstream of LCT as strongly associated with adult-type hypolactasia in families and population samples. | Lower lactase persistence | 0.62 | 0.68 | Open source |
| Olds and Sibley 2003Functional promoter assay Showed the lactase-persistence allele increased lactase promoter activity more than the non-persistence allele in reporter assays. | Lower enhancer support | 0.55 | 0.66 | Open source |
| ClinVar VCV000007685.6Clinical curation record Records rs4988235 in association with lactase persistence and cites the core functional and association literature. | Lactase persistence association | 0.45 | 0.55 | Open source |
Validation
What to check before acting
Real-life pattern
Symptoms after milk, ice cream, whey, or other lactose-containing foods make the DNA signal more relevant.
Objective testing
Lactose hydrogen breath testing or clinician-guided lactose challenge can help confirm whether lactose malabsorption is currently present.
Practical boundary
DNA can point to lower lactase persistence, but symptoms depend on dose, gut state, microbiome, food context, and individual tolerance.
Bottom line
Keep the score, label it correctly
The report can keep the lactose digestion score because the evidence base is valid for the direction. The customer-facing label should frame it as a strong DNA-based follow-up signal, not a measured percent reduction in lactase activity.