NMD-VCell Research Workbench Module: Study design · evidence-to-experiment workflow NMD = neuromuscular disorders
v1.0 candidate Frozen 25 Jul 2026 DOI pending
v1.0.0-database-resource Schema 1.1 Model ridge-safe-v2.3 Benchmark repeated-fold-v2.2 Build EA-20260729-15 v1.0 is a database and evidence-governance release; it is not a validated disease-prediction or clinical decision-support release.
Current evidence ceiling L2 observed HepG2 limited L3a context No independent DMD perturbation validation Open boundary

Stable Study Card 1.5

SC:v1.0.0-database-resource:INTS13:1.5-DRAFTDRAFT

INTS13

risk context review Risk/context review

Does perturbing INTS13 have a context-dependent dependency or toxicity profile that blocks escalation?

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

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 L2 observed same context perturbation Assessment does not imply support
Target closure layer L4 DMD functional validation required
DMD source agreement 100% 4/4 sources · consistent up
Muscle expression 10.99 TPM above 1 TPM context flag
a

Frozen evidence route

  1. L1Resource recordHGNC-resolved typed research object
  2. L2Observed HepG2 perturbation157 observed cells
  3. L3aExternal context screennot assessed
  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 agreement100%
Skeletal-muscle TPM10.99
External screennot assessed
Dependency cautionmoderate
DepMap effect-0.377
c

Evidence-to-experiment route

Context

Matched disease-relevant and non-disease human myogenic contexts plus a tissue-breadth/dependency audit.

Perturb

Dose/time perturbation series only after expression feasibility; include at least two reagents where feasible.

Endpoint

Predeclared viability or essentiality endpoint across dose and time.

Infer

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

Model

Mixed-effects dose-response model with context interaction and blocked reagent 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.

Predeclared design scaffold

Biological context

Matched disease-relevant and non-disease human myogenic contexts plus a tissue-breadth/dependency audit.

Perturbation modality

Dose/time perturbation series only after expression feasibility; include at least two reagents where feasible.

Primary endpoint

Predeclared viability or essentiality endpoint across dose and time.

Primary estimand

Context-by-dose interaction for the primary safety endpoint.

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 context for a pilot dose/time grid; final n requires interaction-effect power analysis.

Randomisation unit

Independent culture well/biological replicate.

Statistical model

Mixed-effects dose-response model with context interaction and blocked reagent estimates.

Decision-blocking gap

GAP-08 Safety and dependency context blocks escalation

Highest missing evidence layer

L4 dmd functional validation

GAP-02 independent muscle-context perturbation; 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

Secondary endpoints

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

Assay QC 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

Primary safety endpoint across frozen doses/times; functional endpoints are secondary.

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

Replication rules

Escalation requires directionally compatible safety estimates from two reagents.

A favourable window must not be attributable to one donor/context.

Stop rules

Time and cost6–12 weeks after model 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.
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.