NMD-VCell Neuromuscular Virtual Cell Research Platform Module: Models · Evidence → perturbation → experiment → outcome NMD = neuromuscular disorders

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

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

CALR perturbation evidence

Perturbation Lab

What happened when this gene was perturbed?Inspect observed responses and clearly labelled no-interaction previews.

Choose a gene and view the observed response, a simple two-gene preview or an external reference.Choose a context, modality and gene first. Counterfactual, interaction and perturbed-fate predictions remain unavailable until matched data exist.

What happened when this gene was perturbed?

CALR was perturbed with CRISPRi in HepG2 cells.

Cell contextHepG2—not a DMD muscle model
Observed readoutFrozen gene-expression response
Muscle / DMD validationNot independently replicated
Next useful experimentControlled myogenic perturbation with replication

Boundary: the pair view is an additive “no-interaction” preview. This is not a predicted double perturbation.

SIM-L0 · observed CRISPRi

CALR observed CRISPRi

Computational replication. This is an observed HepG2 CRISPRi record linked to descriptive program inputs; independent muscle/DMD perturbation replication is absent.

Observed
Observed experiment
CALR
HepG2 response measured Direct evidence in the released assay context
Target disease context
?
DMD muscle not yet tested Matched perturbation data are required
Observed cells86Frozen HepG2 CRISPRi aggregate
Counteralignment0.034Contextual signature relationship; not therapeutic rescue
Skeletal-muscle expression88.63 TPMExpression context, not perturbation validation
Independent DMD replication0Scientific unlock remains unmet

What this means: this page shows measured or clearly bounded reference information. It does not simulate an unmeasured DMD outcome.

Selected-gene external evidence

Context, correction, time-course and calibration evidence

Not a perturbation replication
GSE293514 · human myoblast KOAssessed

Fusion endpoint context only; not DMD rescue.

GSE272233 · DMD correction1/3 significant contrasts

CALR transcript response after DMD editing, not CALR perturbation.

GSE52529 · myogenic time courseMeasured reference

Unperturbed 0/24/48/72-hour reference; perturbed fate remains locked.

GSE133344 · CRISPRa calibrationExpression feature present

Feature presence is not target coverage and does not unlock overexpression.

Descriptive overlap

Descriptive overlap with frozen gene programs

Not formal pathway enrichment
Myogenic / contractile0

No compact-list overlap

ECM / fibrotic0

No compact-list overlap

Inflammatory / stress2

PYCARD, SOD2

Cell cycle / proliferation1

MKI67

Metabolic / secretory2

APOA1, GPX3

Proteostasis / membrane1

GPX3

Response details

Compact response-gene lists

CALR compact response list
APOA1MATN3MT2AMKI67GPX3PYCARDSOD2CRYABCDT1CTNNAL1SYNE1CFB
Server-rendered frozen inputs; descriptive only.
Current boundary

Observed same-HepG2 CRISPRi evidence only; independent DMD validation is absent.

Open CALR evidence record · Open Study Card
Conceptual virtual-cell state transition from a proliferating myoblast through fusion to a mature multinucleated myotube, with molecular, calcium, mitochondrial and membrane readout layers.

Virtual-cell state transition

Perturbation must be tied to state, time and function.

A useful virtual cell should connect an intervention to early molecular response, cell-state transition and late muscle function—while retaining uncertainty and replication status.

MyoblastFusionMyotubeMolecularFunctional
Concept visual · not a measured trajectory or calibrated prediction.
Read the simulation from left to right A perturbation identity is only the first step toward a DMD outcome Colour indicates the strongest evidence currently available at each stage.
DefineGene + CRISPRiHepG2 · endpoint aggregateObserved
0 hTarget perturbation21 singleton aggregatesObserved
6–12 hEarly mechanismResponse-program descriptionPartial
24–48 hCell-state transitionNeeds perturbed time courseLocked
4–7 dDMD functionNeeds myogenic replicationLocked
Pair previewδA + δBInteraction γAB remains unknown until observed doubles exist.

Perturbation evidence and preview ladder

Every view carries its evidence role

No automatic target ranking
SIM-L0Observed single CRISPRiFrozen HepG2 aggregate
SIM-L1Predicted single CRISPRiExperimental; strict direct gate unsupported
SIM-L2Additive “no-interaction” previewδA + δB; interaction omitted · not a predicted double perturbation
SIM-L3Pair interactionNeeds observed doubles
SIM-L4Context and fateKO, OE, muscle transfer and trajectory locked

Capability boundary

Available now versus data required

Available now

Evidence-backed views

  • Observed CRISPRi · 21 frozen HepG2 singleton aggregates
  • Additive hypothesis · δA + δB null preview with no interaction term
  • Reference trajectory · real unperturbed human-myogenic time course
Unavailable · data required

Locked outputs

  • Knockout · matched KO and editing calibration
  • CRISPRa / overexpression · matched muscle or DMD activation response
  • Interaction · observed same-screen doubles
  • Perturbed fate · dynamic perturbation sampling

Locked items expose only their unlock conditions; they do not emit simulated values.

External evidence registry

Four public reference datasets are qualified—each with a different permitted role

The cards separate direct perturbation evidence, muscle phenotype screening, DMD correction, unperturbed myogenic time evolution and cross-cell-line CRISPRa-combination calibration.

No candidate-level DMD replication
Current substrateHepG2 CRISPRi

21 observed single perturbations remain the only direct response substrate in the browser.

Direct candidates
21
Observed doubles
0
Direct · context-limited
GSE293514Human myoblast fusion screen

Stage B0 now exposes the observed healthy-human-myoblast network; absence from the fusion-hit set remains endpoint-specific.

Published screen hits
250
Individual validation
125
Observed function · not DMD
GSE272233DMD CRISPR-correction reference

Bulk RNA-seq from three exon-duplication backgrounds and matched corrected clones; candidate transcripts are observations, not candidate perturbation effects.

Samples
21
Correction DE calls
5923
Orthogonal reference
GSE52529Human myogenic time course

Primary human skeletal myoblast single cells at 0, 24, 48 and 72 hours, with distributed pseudotime and state assignments.

Cells
271
Candidate coverage
20/21
Reference only · not perturbed
GSE133344CRISPRa + pair calibration

K562 single and combinatorial CRISPRa benchmark. It calibrates method design, not muscle-context candidate overexpression effects.

Reported perturbations
287
Feature coverage
20/21
Method calibration only

Unlock conditions

What the next data release must add

True knockoutMatched KO observations

Editing efficiency, residual expression, controls and context-matched outcomes; CRISPRi cannot be relabelled as KO.

OverexpressionMatched muscle CRISPRa/OE data

GSE133344 now calibrates study and pair design, but activation dose and expression response must be observed in muscle/DMD context; the negative of a knockdown response is not accepted.

Pair interactionObserved double perturbations

Same-screen singletons and doubles with pair-disjoint validation before estimating γAB, synergy or synthetic rescue.

Perturbed trajectoryPair perturbation with dynamic sampling

GSE52529 supplies the unperturbed 0/24/48/72-hour reference. Candidate-conditioned velocity or fate still requires matched perturbation cells sampled across the lineage.

Boundary. The program lens is a descriptive overlap display, not formal pathway enrichment. The pair view is an additive hypothesis, not an observed double perturbation. No output is a treatment, safety, causal-mechanism or clinical recommendation.