NMD-VCell Neuromuscular Virtual Cell Research Platform Module: Design · Evidence → perturbation → experiment → outcome NMD = neuromuscular disorders
For Reviewers Current Release

Release 2026.08DMD context observedDMD candidate-conditioned prediction not yet eligible

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Evidence freeze: 3 August 2026 Resource: v1.2.0-measured-dmd-evidence Schema: 1.1 Open release status →

Execution amendment · v08.8 draft

A governed path from sensitivity result to accountable execution.

One shared evidence base · three accountable review lanes · prospective randomization and outcome access remain sealed until external registration.

Open evidence-to-experiment bridge

ADAM10 Study Card

Prospective design sensitivity · v08.7

ADAM10 remains a bounded two-pair pilot.

Standardized simulation: 480 scenarios × 20,000 replicates; independent server repeat exact. This is not an observed DMD outcome or efficacy claim.

Formal lockBLOCKED · 39 inputs pendingOpen synchronized evidence object

Truth-generation Study Card

SC:v1.2.0-measured-dmd-evidence:ADAM10:1.5-DRAFTDRAFT

ADAM10

computational replication Computational replication

Does the ADAM10 evidence pattern replicate in an independent dataset under a frozen analysis plan?

Registration completeness50%
Missing before registration
  • direction rationale
  • numeric minimally important effect
  • numeric negligible-effect margin
  • final powered sample size

Decision summary

ADAM10 is ready for a bounded next step, not a DMD response claim.

Does the ADAM10 evidence pattern replicate in an independent dataset under a frozen analysis plan?

What we know
observed same context perturbation
What remains uncertain
GAP-07 Independent computational replication is absent
Experiment entry state
Draft design; registration fields remain open
Next action
Computational replication
Lifecycle track
Generate new truth. A prediction is not required for this study.
First fields to close
  • direction rationale
  • numeric minimally important effect
  • numeric negligible-effect margin
  • final powered sample size
Continue the designInspect the evidence

Study Freeze Gate

Complete the required design fields before creating a review-ready frozen dossier.

Readiness: 50% · 4 required fields remain open.

Complete required fields

Freezing creates an immutable, checksum-bound Study dossier. External registration remains a separate authority action.

Research object trace

GENE:v1.2.0-measured-dmd-evidence:ADAM10 → comparison-not-available → PLN:v1.2.0-measured-dmd-evidence:ADAM10:1.0-DRAFT → SC:v1.2.0-measured-dmd-evidence:ADAM10:1.5-DRAFT → OUT:v1.2.0-measured-dmd-evidence:ADAM10:PENDING

Traceability only; object links do not register a prediction or measured DMD outcome.

SuggestedSelectedFrozenMeasuredCurrent protocol values are suggestions until experimental authority selects and freezes them.

Study Card visual summary

Frozen evidence and registration route

This multi-panel view turns the frozen Study Card fields into a visual audit of what is known, what is missing and what must be registered next.

BoundaryDescriptive frozen evidence snapshot only; no score, rank, cluster, prediction claim or intervention recommendation is generated.
Registration readiness 50% 4 open fields
Current supported level L2 observed same context perturbation Observed evidence ceiling in this record
Highest assessed context L3a external context screen Assessment does not imply support
Target closure layer L4 DMD functional validation required
DMD source agreement 50% 2/4 sources · conflicted
Muscle expression 3.12 TPM above 1 TPM context flag
a

Frozen evidence route

  1. L1Resource recordHGNC-resolved typed research object
  2. L2Observed HepG2 perturbation161 observed cells
  3. L3aExternal context screenassessed no current hit
  4. L3bIndependent perturbation replicationsame-perturbation replication absent
  5. L4DMD muscle functional validationDMD-relevant functional validation absent
  6. REGRegistered Study Card4 open fields before registration
b

Bioinformatics result snapshot

Legacy integrated DMD priorup
Source agreement50%
Skeletal-muscle TPM3.12
External screenassessed no hit
Dependency cautionnot flagged
DepMap effect0.012
c

Evidence-to-experiment route

Context

At least one independent dataset with declared tissue/cell state, disease status and gene-mapping coverage.

Perturb

No new wet-lab perturbation is nominated; rerun the frozen direction, pathway and robustness analyses.

Endpoint

Predeclared gene-level direction or effect estimate in the independent dataset.

Infer

Independent biological replicate or independently generated perturbation unit; cells within one aggregate are not inferential replicates.

Model

Dataset-appropriate pseudobulk or aggregate model with donor/sample as the inferential unit.

d

Registration gap map

  • direction rationale
  • numeric minimally important effect
  • numeric negligible-effect margin
  • final powered sample size

These bars are field-state indicators only. They do not create a target score, rank, cluster or prediction claim.

Field state · Suggested

Design options for experimental review

Biological context

At least one independent dataset with declared tissue/cell state, disease status and gene-mapping coverage.

Perturbation modality

No new wet-lab perturbation is nominated; rerun the frozen direction, pathway and robustness analyses.

Primary endpoint

Predeclared gene-level direction or effect estimate in the independent dataset.

Primary estimand

Independent-dataset gene effect and uncertainty under the frozen contrast.

Inferential unit

Independent biological replicate or independently generated perturbation unit; cells within one aggregate are not inferential replicates.

Planning sample size

One or more independent datasets; donor/sample adequacy must be justified from the source design rather than a generic target count.

Randomisation unit

Independent donor/sample/study unit defined by the source dataset.

Statistical model

Dataset-appropriate pseudobulk or aggregate model with donor/sample as the inferential unit.

Decision-blocking gap

GAP-07 Independent computational replication is absent

Highest missing evidence layer

L4 dmd functional validation

GAP-02 independent muscle-context perturbation; GAP-03 DMD-relevant functional validation

Perturbation-direction rationale

Current selection: unresolved requires registration

State whether the disease-associated direction is hypothesized as causal, compensatory or accompanying, and preserve the opposite-direction alternative. DMD direction and counteralignment never choose an intervention automatically.

Allowed registered hypotheses: activation; inhibition; bidirectional exploration; direction not identifiable.

Comparator and controls

  • Frozen null and simple baselines.
  • Leave-one-source-out analysis.
  • Negative-control genes or permuted labels.
  • Complete unmatched-identifier report.

Secondary endpoints

  • Pathway concordance.
  • Leave-one-source-out robustness.
  • Coverage and null-result diagnostics.

State-transition extension

Mechanism hypothesis and registered time axis

Scientific object: perturbation × cell state × disease context × time × phenotype

Required before registration: state the proposed early molecular mediator, the expected cell-state transition and the downstream functional consequence.

6–12 hearly molecular or signalling response

planning default requires assay calibration

24–48 hregulatory program and cell-state transition

planning default requires assay calibration

4–7 ddifferentiation and functional phenotype

planning default requires assay calibration

Cell context fields

Required before registration: healthy, DMD or isogenic corrected. Required before registration: proliferating myoblast, early differentiation, fusion or maturing myotube. Required before registration; preserve donor-specific estimates.

Cell–cell consequence

Current status: not assessed. Future levels: conditioned medium; two-cell co-culture; three-dimensional muscle model; spatial perturbation model.

Blocking factors

  • Study/donor.
  • Batch.
  • Cell state.
  • Dataset-specific covariates.

Assay QC thresholds

  • Minimum donor/sample coverage.
  • Gene detectability.
  • Frozen mapping and exclusion thresholds.

Minimally important effect

Required before registration; derive from assay biology or a justified pilot and store the numeric value with units.

Negligible-effect margin

Required before interpreting a null result; store a symmetric or asymmetric numeric margin with units.

Multiplicity and missing data

Frozen gene and pathway families with declared adjustment method.

Define exclusions before unblinding; report all missing units and reasons; do not single-impute primary outcomes without a prespecified sensitivity analysis.

Replication rules

Not applicable unless the independent dataset contains multiple perturbation reagents.

A result must persist beyond a single donor/sample and disclose leave-one-unit-out sensitivity.

Stop rules

  • Stop or classify as infeasible if a required numeric QC threshold fails.
  • Do not interpret a nonsignificant result as no material effect without a negligible-effect interval.
  • Do not change canonical candidate status automatically; require governed review.
Time and cost1–4 weeks after data access; planning estimate only. Institution- and assay-dependent; obtain a local itemised quote before registration.
Preregistration statusdraft requires direction rationale numeric effect margin sample size and qc thresholds
Lifecycle ruleThis draft is editable. Registration requires a timestamp and checksum; a registered revision is immutable and any correction must supersede it.
Escalation ruleEscalate from L2 to L3b only after independent context-matched perturbation replication; L4 requires replicated DMD-relevant muscle evidence.
Evidence transitionCurrent evidence state → predeclared independent test → governed evidence-level review.

Version history

Study Card 1.4 → 1.5

Field groupChangeScientific effect
Object identityCard schema and object version advanced to 1.5.Traceability only
State-transition designCell context, timepoint roles, mechanism hypothesis and cell–cell consequence fields added.Design scaffold expanded
Frozen evidenceNo supporting evidence, evidence level or outcome was added.Unchanged

This is a draft-to-draft schema revision, not a registered-study amendment and not an evidence upgrade.

Data-release planRelease the frozen card, protocol identifiers, analysis code, complete denominators and results irrespective of direction; never overwrite the registered card.
Boundary: This Study Card is an evidence-gated design scaffold, not a protocol, power calculation, safety claim, prediction or therapeutic recommendation.