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 →

ZNF133 Study Card

Truth-generation Study Card

SC:v1.2.0-measured-dmd-evidence:ZNF133:1.5-DRAFTDRAFT

ZNF133

muscle perturbation Muscle-context assay

Does perturbing ZNF133 change one predeclared muscle phenotype in an independent human myogenic model?

Registration completeness38%
Missing before registration
  • direction rationale
  • numeric minimally important effect
  • numeric negligible-effect margin
  • QC thresholds
  • final powered sample size

Decision summary

ZNF133 is ready for a bounded next step, not a DMD response claim.

Does perturbing ZNF133 change one predeclared muscle phenotype in an independent human myogenic model?

What we know
observed same context perturbation
What remains uncertain
GAP-02 Independent muscle-context perturbation is absent
Experiment entry state
Draft design; registration fields remain open
Next action
Muscle-context assay
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
  • QC thresholds
  • 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: 38% · 5 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:ZNF133 → CMP-20260726-A04D03258188 → PLN:v1.2.0-measured-dmd-evidence:ZNF133:1.0-DRAFT → SC:v1.2.0-measured-dmd-evidence:ZNF133:1.5-DRAFT → OUT:v1.2.0-measured-dmd-evidence:ZNF133: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 38% 5 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 75% 3/4 sources · conflicted
Muscle expression 4.56 TPM above 1 TPM context flag
a

Frozen evidence route

  1. L1Resource recordHGNC-resolved typed research object
  2. L2Observed HepG2 perturbation84 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 Card5 open fields before registration
b

Bioinformatics result snapshot

Legacy integrated DMD priorup
Source agreement75%
Skeletal-muscle TPM4.56
External screenassessed no hit
Dependency cautionnot flagged
DepMap effect-0.038
c

Evidence-to-experiment route

Context

Human myoblast or myotube model; healthy/DMD/isogenic background and differentiation state declared before registration.

Perturb

CRISPRi, CRISPRa or siRNA selected for the biological question; at least two independent reagents where feasible.

Endpoint

One predeclared functional muscle endpoint such as fusion, morphology or contractile readout.

Infer

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

Model

Mixed-effects model with treatment fixed effect and donor/batch/reagent blocking; report reagent-specific estimates.

d

Registration gap map

  • direction rationale
  • numeric minimally important effect
  • numeric negligible-effect margin
  • QC thresholds
  • 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

Human myoblast or myotube model; healthy/DMD/isogenic background and differentiation state declared before registration.

Perturbation modality

CRISPRi, CRISPRa or siRNA selected for the biological question; at least two independent reagents where feasible.

Primary endpoint

One predeclared functional muscle endpoint such as fusion, morphology or contractile readout.

Primary estimand

Between-condition mean difference (or prespecified ratio) in the primary functional endpoint at the frozen time point.

Inferential unit

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

Planning sample size

3–6 independent biological replicates per condition and reagent as a pilot planning range; final n requires assay variance and minimally important effect.

Randomisation unit

Independent culture well or biological replicate, not individual cells.

Statistical model

Mixed-effects model with treatment fixed effect and donor/batch/reagent blocking; report reagent-specific estimates.

Decision-blocking gap

GAP-02 Independent muscle-context perturbation is absent

Highest missing evidence layer

L4 dmd functional validation

GAP-03 DMD-relevant functional validation; GAP-07 independent replication

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

  • Non-targeting control.
  • Positive assay control.
  • Mock delivery control when delivery itself can affect phenotype.
  • Target-engagement and viability controls.

Secondary endpoints

  • Target engagement.
  • Viability/toxicity.
  • Directional transcriptomic response.

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

  • Donor/isogenic pair.
  • Differentiation batch.
  • Plate and reagent identity.

Assay QC thresholds

  • Target-engagement threshold must be numeric and frozen.
  • Viability floor and image-quality thresholds must be numeric and frozen.

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

Primary endpoint across the two reagents; secondary endpoints form a separate multiplicity family.

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

Replication rules

Both reagents must agree in direction and neither may fail the engagement/QC gate; discordance is inconclusive.

Direction must replicate beyond a single donor or isogenic pair before L4 escalation.

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 cost6–12 weeks after model and reagent readiness; 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.