Stable server-rendered gene record · v1.2.0-measured-dmd-evidence

ADAM10

Computational replication

G4 · muscle-context screen, not DMD replicationR2 · muscle-context bridge evidenceSupported · L2 observed same context perturbationAssessed · L3a external context screen

What this meansADAM10 has been experimentally perturbed in HepG2 cells, but it has not been independently perturbed in a DMD muscle model. Different DMD datasets do not completely agree on its disease-associated direction. The next useful step is computational replication—not a therapeutic claim.

通俗解释ADAM10已经在HepG2细胞中做过扰动，但尚未在DMD肌肉模型中独立验证。不同DMD数据集对它的疾病相关方向并不完全一致。下一步应完成能弥补当前证据缺口的受控实验，而不能把它直接称为治疗靶点。

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Prediction readinessR2 · muscle-context bridge evidence

Current evidenceObserved perturbation in the same HepG2 context

Additional contextAssessed · no current hit

Historical DMD prior (legacy)up

Source agreement2/4 sources

Open core JSON Complete typed record Historical detailed audit

Gene Entity Page 2.1 · quantitative layer

Dataset-level evidence for ADAM10

Every row keeps its original context, metric and denominator. Empty fields remain explicit; no cross-source meta-effect is computed.

Download evidence JSON →

IdentityReleasedHGNC:188 · ENSG00000137845

PerturbationMeasured in HepG2161 contributing cells

Muscle contextScreen assessed3.1162 TPM in skeletal muscle

DMD context4 source rowsDirectional conflict retained

DMD perturbation truthMissingNo independent DMD-muscle perturbation outcome

Calibrated predictionLockedR2 · no calibrated DMD response model

Dataset-level evidence rows for ADAM10
Dataset / evidence	Context and endpoint	Observed value	Denominator / support	State and source
HEPG2_CRISPRI_FROZEN_AGGREGATEperturbation observation	Eligible cells contributing to the frozen target-level aggregateHepG2; CRISPRi; non-muscle, non-DMD context	161 cells	161 cells	measuredOpen sourceObserved perturbation coverage in HepG2. The cells are not independent biological replicates and do not establish a DMD effect.
GTEX_V8_SKELETAL_MUSCLEexpression context	Expression feasibility contextHuman skeletal muscle tissue	3.1162 TPM	1 contexts · row count unavailable	context onlyOpen sourceTissue expression supports assay feasibility only; it does not establish cell-type expression, function or perturbation response.
DEPMAP_CONTEXT_METRICdependency context	Median gene-effect context metricDepMap cell-line dependency context; not muscle-specific	0.012093 DepMap gene-effect score	Denominator not carried	context onlyOpen sourceA broad dependency context metric. It is not a safety result and is not evidence of disease-selective dependency.
HEPG2_CONTEXT_RELATIONSHIP_V06context relationship	Contextual signature relationshipSame processed HepG2 perturbation substrate	0.016578 unitless score	161 cells contributing to the target aggregate	context onlyOpen sourceA descriptive relationship within the same processed context; it is not therapeutic rescue or an independently validated effect.
GSE293514screen result	Fusion-positive enrichmentHealthy human myoblast fusion CRISPR screen	-0.075195 log fold-changeFDR 0.999999	1 contexts · 1 rows0 significant rows	assessed no hitOpen sourceHealthy-myoblast fusion endpoint only. A no-hit result is endpoint-specific and is not evidence of no muscle or DMD effect.
DMD single-cell baseline pseudobulkdisease context effect	Disease-associated baseline expressionDMD skeletal-muscle single-cell source; baseline pseudobulk summaries	-0.168192 source-specific effect scaleMedian signed score -0.00000456	21 contexts · 21 rows0 significant rows	context onlyOpen sourceObserved-expression source summary; contextual evidence rather than candidate perturbation truth.
DMD single-cell delta / DIDdisease context effect	Disease-associated change across declared contextsDMD skeletal-muscle single-cell source; final-label delta / DID summaries	0.188389 source-specific effect scaleMedian signed score 0.00000248	20 contexts · 20 rows0 significant rows	context onlyOpen sourceObserved-expression source summary; contextual evidence rather than candidate perturbation truth.
SEMA3C DESeq2 source-statedisease context effect	Source-specific differential expressionDMD skeletal-muscle source-state analysis	0.171343 source-specific effect scaleMedian signed score 0.00001158	9 contexts · 9 rows0 significant rows	context onlyOpen sourceObserved-expression source summary; contextual evidence rather than candidate perturbation truth.
SEMA3C NicheNet target-statedisease context effect	Inferred target-state relationshipDMD skeletal-muscle regulatory-inference context	-0.029278 source-specific effect scaleMedian signed score -0.00399435	2 contexts · 2 rows0 significant rows	context onlyOpen sourceRegulatory-inference channel; displayed separately and not pooled as an independent expression cohort.

Source-specific effect display

DMD source-effect forest

Position is scaled to the largest absolute effect shown for this gene. Values remain on source-specific scales and are not pooled.

sc baseline pseudobulk-0.16819221 contexts · 0/21 significant rows

sc delta/DID+0.18838920 contexts · 0/20 significant rows

DESeq2 source-state+0.1713439 contexts · 0/9 significant rows

NicheNet target-state-0.0292782 contexts · 0/2 significant rows

independent dmd muscle perturbationmissing not negativeUnlock: Run an independent, quality-controlled perturbation in a declared DMD-relevant human myogenic model with biological replication.

per gene deg pathway and cell state profilesource context summary only dmd perturbation missingUnlock: The v1.7 bridge publishes a HepG2 source-context summary and cross-DMD-source pathway projections. A disease-matched candidate perturbation with a biological denominator remains required.

calibrated dmd response predictionlockedUnlock: Accumulate prospective DMD perturbation outcomes and pass the registered calibration, applicability and external-validation gates.

Dataset rows preserve their original context and scale. They are not pooled into a causal effect, therapeutic rank or calibrated DMD prediction.

Frozen candidate bridge · PCB-v0.2-20260804

Cross-context DMD statistical bridge

Measured HepG2 response is compared with three separately measured DMD pathway axes. Individual source results come first; pooled values are exploratory descriptive summaries only.

Download all 21 rows →

Measured candidate DMD perturbations0/21

Validated candidate-level predictions0

Cross-context projection is not a measured ADAM10 response in DMD muscle and does not establish rescue, efficacy, or a target rank.

HepG2 candidate / control cells161 / 4,976Cell-level exploratory comparison; no biological-replicate column.

Target-gene delta-0.30044Target present in the expression panel.

Exploratory DE rows415592 rows at cell-level FDR < 0.05; donor/disease inference blocked.

Robust Reactome pathways33193 up · 238 down of 1,378 tested.

Cross-DMD-source pathway projections for ADAM10
Measured DMD source	Direct projection ρ	Cascade projection ρ	Statistical unit and ceiling
GSE233606	0.192991,360 pathways	0.161051,360 pathways	one line per condition3566 cells · descriptive unselected gene-axis concordance
GSE272233	0.342081,320 pathways	0.331521,320 pathways	3 reported biological repeats per group21 samples · background-specific correction response
GSE277637	0.001781,360 pathways	0.076851,360 pathways	4 lines with one shared WT10480 cells; 4 pseudobulks · line-specific descriptive effects

Direct projection heterogeneityI² 97.6% · Q 84.4Pooled ρ 0.18084 · source direction consistent

Cascade projection heterogeneityI² 96% · Q 49.76Pooled ρ 0.19081 · source direction consistent

DMD-correction alignmentρ 0.214491,320 pathways · contextual alignment, not candidate validation.

Bridge projection statePROVISIONAL CROSS CONTEXT PRIORITY REQUIRES DMD PERTURB SEQL2 CROSS CONTEXT NETWORK HYPOTHESIS ONLY · does not override the governed current action or create a rank.

Why validation is still required

No additional abstention reason recorded; disease-matched validation is still required.

Bridge JSON Statistical contract Manifest + SHA-256 ADAM10 evidence TSV

Pathways overlap and the three source vectors are not independent studies. HepG2 cell-level statistics support source-context exploration only. The disease-matched functional-validation gate remains open.

What this candidate is for

Does the ADAM10 evidence pattern survive an independent dataset and frozen analysis workflow?

A candidate record authorizes a bounded question and next experiment. It does not authorize a therapeutic or clinical claim.

GAP-07

Practical useDecide whether the computational signal is reproducible enough to justify experimental escalation.

Decision available nowExperimental escalation remains provisional until the signal is independently reproduced.

What blocks itIndependent computational replication is absent

Minimum next actionRepeat the ADAM10 analysis with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.

How would the result change the decision?

SupportiveRetain the candidate and move to its next context-specific gate if direction and uncertainty reproduce.

NullRetain the negative result and do not escalate from the original analysis alone if replication fails with adequate QC.

Inconclusive / QC failureMark the replication non-evaluable when coverage, mapping or source design prevents a fair test.

Open Study Card Plan the experiment Compare decision gaps

Gene Entity Page 2.1

Entity graph: identity, evidence and prospective objects

This chain shows which objects exist for ADAM10, which are still drafts and which registries are empty. Empty is not a negative experimental result.

v1.2.0-measured-dmd-evidence

Object IDGENE:v1.2.0-measured-dmd-evidence:ADAM10

HGNCHGNC:188

EnsemblENSG00000137845

NCBI Gene102

Disease scopeDMD evidence context

01 · Gene objectRELEASEDStable identity and typed core record

02 · Evidence objectObserved · context-boundedNo DMD perturbation truth is implied

03 · Model gateR2 · R2 · muscle-context bridge evidencePredictionReadiness governance state

04 · Study objectDRAFT · editableCandidate Study Card available

05 · Prediction objectEMPTYNo immutable prospective prediction

06 · Outcome objectEMPTYNo linked measured outcome

Core JSON Compare evidence Open draft Study Card Prediction registry

Claim boundary: object connectivity improves traceability; it does not raise the evidence tier or authorize a therapeutic claim.

Gene visual profile · 基因证据剖面

One-page evidence profile for ADAM10

A four-panel, descriptive view of the same bounded gene record: evidence depth, DMD source matrix, context gauges and the current decision gap. No score, target rank or prediction claim is computed.

Evidence profile

L1 resourceStable record released
L2 HepG2 perturbationassessed
L3a external screenAssessed · no current hit
L3b independent replicationNot assessed
L4 DMD / muscle validationMissing
L5 therapeutic / clinicalUnsupported

DMD source matrix

sc baseline pseudobulkNegative source directionMedian effect -0.168192 · signed score -0.00000456observed expression · 21 contexts · 0/21 significant rows

sc delta/DIDPositive source directionMedian effect +0.188389 · signed score 0.00000248observed expression · 20 contexts · 0/20 significant rows

DESeq2 source-statePositive source directionMedian effect +0.171343 · signed score 0.00001158observed expression · 9 contexts · 0/9 significant rows

NicheNet target-stateNegative source directionMedian effect -0.029278 · signed score -0.00399435regulatory inference · 2 contexts · 0/2 significant rows

Observed-expression and regulatory-inference channels are displayed side by side and are not pooled as independent cohorts.

Context gauges

Source agreement2/4 sources

This measures agreement among source pipelines; it is not biological ground truth.

Muscle expression3.116 TPM

Visual guide; ≥1 TPM is the current triage threshold.

Cells contributing to the aggregate161

Coverage count, not a power calculation.

External screenAssessed · no current hit

This no-hit result is specific to the fusion-screen endpoint; it does not show that the gene has no muscle function.

Gap ladder

GAP-07Independent computational replication is absent

Current actionComputational replication
Highest missing layerL4 dmd functional validation
Claim boundaryNo P1/P2 prediction claim unlocked

Interpretation boundary: this visual profile reorganizes frozen fields for inspection. It does not create a source-balanced successor result, a causal conclusion, a therapeutic direction or a clinical decision-support claim.

Decision boundary

What must be resolved next

Decision-blocking gapGAP-07 · Independent computational replication is absent

Highest missing layerL4 dmd functional validation

Readiness upgrade requiredRun an independent DMD/control myogenic perturbation with predeclared molecular, state and functional endpoints.

The decision-blocking gap is the next missing layer that prevents the current action from advancing. The highest missing layer is the longer-term evidence ceiling; it is not necessarily the next experiment.

DMD context

Source-state record

DMD source-state fields for ADAM10
Direction state	conflicted
Variant stability	sign varied across variants
Evidence modules	direction conflicted
Statistical support	direction only no significant context rows
Coverage	4 of 4 sources
Uncertainty	direction conflict retained

Identifiers and context

Machine-resolvable core

Machine-resolvable identifiers and context for ADAM10
HGNC	HGNC:188
Ensembl	ENSG00000137845
NCBI Gene	102
HepG2 perturbation	assessed
HepG2 observed cells	161
Observed counteralignment	0.01657791
Myoblast screen	assessed
Myoblast fusion-screen effect	-0.075195 log fold-change
Myoblast fusion-screen FDR	0.999999
Skeletal-muscle expression	3.1162 TPM
DepMap median gene effect	0.01209277

Cite this record

Stable identity

Object ID: GENE:v1.2.0-measured-dmd-evidence:ADAM10

NMD-VCell. ADAM10 evidence record. Resource v1.2.0-measured-dmd-evidence; evidence freeze 2026-08-03; schema 1.1; build EA-20260817-57. DOI pending.

Schema 1.1 · evidence freeze 2026-08-03 · build EA-20260817-57 · one of 17,921 stable core records.