Pathway-to-Model Reference Chart: Key Genes × Recommended Cell Models

A one-page answer to the question that precedes every model build.

What This Chart Is

Forty gene and pathway entries, each mapped to four things:

  • • the question the gene is usually studied to answer,
  • • the model that can answer it,
  • • the readout that carries weight,
  • • and the artefact most often mistaken for a result.

It exists because the most common model failure is not technical. It is choosing a cell system that cannot express the pathway in question, then interpreting the absence of a phenotype as biology. The chart makes that mismatch visible before the build.

How to Use It

StepWhat you doWhy
1Find the gene or the closest pathway nodePathway-level entries apply when the specific gene is one of several paralogues
2Read the recommended modelIf that model is unavailable, treat the row as a constraint, not a suggestion
3Design the assay from the readout columnA model without the readout produces no interpretable data
4Read the last column before committingIt names the artefact reviewers will look for

The full chart is a two-sheet spreadsheet: the matrix itself, and a "how to use" page with the three rules that apply to every row.

Sample Rows

Gene / nodePathwayRecommended modelPrimary readoutWatch out for
YAP1HippoMCF10A or HEK293 at controlled densityYAP nuclear fraction; TEAD reporterTotal YAP is not activity
CTNNB1WNTCRC line with defined APC statusNuclear β-catenin; AXIN2Reporter activation ≠ canonical WNT
PTENPI3K–AKTIsogenic PTEN knockoutpAKT; FOXO localizationpAKT is transient
PDCD1Immune checkpointPrimary T cells, RNP deliveryCytokine output; killingDonor variability and activation state
GCKGlucose handlingiPSC-derived β cellsInsulin secretion vs glucoseLine must retain secretion
KRASMAPK dependencyIsogenic G12C/D panel, lineage-matchedGrowth; pERKCo-occurring lesions dominate

Forty entries cover Hippo, WNT, PI3K–AKT, immune checkpoints and targets, hepatic and β-cell metabolism, fatty-acid oxidation and glycolysis, common cancer dependencies, and the neurodegeneration genes most often modelled in iPSC-derived cells.

Three Rules That Apply to Every Row

A model that lacks the pathway cannot report on it. Check baseline pathway activity in the model before editing anything. A knockout in a line where the pathway is already off will look inert, and that is a statement about the line.

One readout is never enough. Pair a pathway-state readout (localization, phospho-signal, reporter) with a functional endpoint (growth, secretion, killing). The first explains the mechanism; the second shows it matters.

Context is part of the claim. Lineage, passage, stimulation and media all change pathway state. A row in this chart tells you what to measure, not what you will find.

Need the chart applied to your target?

Send us the gene or pathway node and the cell type you have access to. We will tell you whether the model can support the question, which readout to build first, and what the pilot should look like — before a single guide is ordered.

Contact EDITGENE to request a project consultation or quote.

Scientific scope and validation note

Entries reflect common practice across published work; model performance varies by protocol, passage, and donor. The chart is a planning aid, not a protocol library.

Every recommendation should be confirmed with a pilot in the intended cell type before a build is committed.

Selected references for further reading

  • • Tsherniak A, et al. Defining a cancer dependency map. Cell. 2017;170:564–576.
  • • Nott A, et al. Brain cell type-specific enhancer–promoter interactome maps and disease-risk association. Science. 2019;366:1134–1139.
  • • Fruman DA, et al. The PI3K pathway in human disease. Cell. 2017;170:605–635.

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