Applicability and evidence gaps

Evidence levels

One shared ladder across gene pages and the Workbench

Level	Definition
L1	Resource record and technical completeness
L2	Observed perturbation or model support within the same HepG2 background
L3a	External-context screen; not the same perturbation replication
L3b	Same perturbation replicated in an independent dataset
L4	Functional validation in a DMD-relevant muscle background
L5	Therapeutic or clinical utility

Disease Module Explorer

Disease	Module depth	Perturbation data	Disease prior	Functional data
DMD	Full beta	HepG2 only	Legacy integrated prior; source conflict retained	Not covered in current release
SMA	Indexed	Limited HepG2 coverage	Not built	Missing
ALS/FTD	Indexed	Limited HepG2 coverage	Not built	Missing
Other NMD	Indexed	Gene-dependent	Not built	Missing

Coverage, not biological truth. For a disease gene such as DMD, “not supported in the current atlas” means that this release lacks an eligible direct DMD-gene perturbation record. It does not mean the gene is unrelated to the disease, functionally inactive or a negative result.

Page-specific boundary. Evidence labels describe what was measured and where. Missing coverage is not a negative result, and L1–L2 support cannot be promoted to muscle/DMD, target, therapeutic or clinical validity.

Coverage by evidence level

Current applicability matrix
Evidence layer	Coverage	Level	Supported use	Unsupported inference
Technical aggregate reliability	Resource-wide	L1	Query, audit and reproduce released objects	Biological or clinical validity
Observed HepG2 candidate perturbation	21/21	L2	Bounded same-HepG2 hypothesis triage	Muscle or DMD target validation
Human-myoblast fusion phenotype	9/21 assessed; 0/9 current hits	L3a external context screen (not perturbation replication)	Coverage-aware risk/exclusion review	Safety, efficacy or a negative result for 12 unassessed genes
Independent muscle/DMD perturbation transcriptome	0/21	L4 unsupported	Evidence-gap declaration	Disease-relevant perturbation validity
Therapeutic or clinical utility	0 validated endpoints	L5 unsupported	None in this release	Treatment benefit or clinical recommendation

What evidence is needed next?

NMD scope records and next-data needs
gene	disease_family	disease_group	mechanism_group	in_hepg2_trade	n_cells	support_level	nar_claim_language	next_data_need
SETX	ALS/FTD-spectrum	ALS4/ataxia	rna_dna_helicase	True	92	direct_benchmarkable	Can support direct perturbation-response and benchmark interpretation in current HepG2 TRADE context.	Add disease-relevant muscle or neuron context for biological specificity.
TARDBP	ALS/FTD-spectrum	ALS	rna_binding	True	262	direct_low_power_or_caution	Can support boundary analysis; direct response exists but needs caution from low cell count or safety/dependency flags.	Increase perturbation support or validate in a more relevant context.
SOD1	ALS/FTD-spectrum	ALS	motor_neuron_oxidative	True	24	direct_sparse_boundary	Only sparse perturbation evidence; use as coverage boundary, not a predictive claim.	Need stronger perturbation support before candidate prioritization.
C9orf72	ALS/FTD-spectrum	ALS/FTD	repeat_expansion	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
FUS	ALS/FTD-spectrum	ALS	rna_binding	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
MATR3	ALS/FTD-spectrum	distal myopathy/ALS overlap	rna_binding	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
NEFL	ALS/FTD-spectrum	CMT/ALS overlap	neurofilament	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SQSTM1	ALS/FTD-spectrum	multisystem proteinopathy/ALS overlap	autophagy	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
TIA1	ALS/FTD-spectrum	distal myopathy/ALS overlap	rna_binding	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
DNM2	CMT/peripheral-neuropathy	centronuclear myopathy/CMT	membrane_trafficking	True	14	direct_sparse_boundary	Only sparse perturbation evidence; use as coverage boundary, not a predictive claim.	Need stronger perturbation support before candidate prioritization.
HSPB1	CMT/peripheral-neuropathy	CMT/dHMN	chaperone	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
HSPB8	CMT/peripheral-neuropathy	CMT/dHMN	chaperone	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
DMD	DMD/BMD	Duchenne/Becker muscular dystrophy	muscle_membrane	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SGCA	DMD/BMD	sarcoglycanopathy/LGMD	dystrophin_complex	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SGCB	DMD/BMD	sarcoglycanopathy/LGMD	dystrophin_complex	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SGCD	DMD/BMD	sarcoglycanopathy/LGMD	dystrophin_complex	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SGCG	DMD/BMD	sarcoglycanopathy/LGMD	dystrophin_complex	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SMN2	SMA/motor-neuron	spinal muscular atrophy modifier	motor_neuron_rna	True	452	direct_benchmarkable_candidate_queue	Can support direct perturbation-response and benchmark interpretation in current HepG2 TRADE context.	Add disease-relevant muscle or neuron context for biological specificity.
DYNC1H1	SMA/motor-neuron	SMA-LED/CMT	motor_neuron_transport	True	35	direct_low_power_or_caution	Can support boundary analysis; direct response exists but needs caution from low cell count or safety/dependency flags.	Increase perturbation support or validate in a more relevant context.
BICD2	SMA/motor-neuron	SMA-LED	motor_neuron_transport	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
GARS1	SMA/motor-neuron	CMT/SMA	trna_synthetase	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
IGHMBP2	SMA/motor-neuron	SMARD1	helicase	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
SMN1	SMA/motor-neuron	spinal muscular atrophy	motor_neuron_rna	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
VRK1	SMA/motor-neuron	motor neuron disease	kinase	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
GMPPB	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	True	36	direct_low_power_or_caution	Can support boundary analysis; direct response exists but needs caution from low cell count or safety/dependency flags.	Increase perturbation support or validate in a more relevant context.
ACTA1	muscular-dystrophy/myopathy	actin myopathy/nemaline myopathy	sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
ANO5	muscular-dystrophy/myopathy	ANO5 myopathy/LGMD	membrane_repair	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
B3GALNT2	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
BAG3	muscular-dystrophy/myopathy	myofibrillar myopathy	protein_quality_control	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
BIN1	muscular-dystrophy/myopathy	centronuclear myopathy	t_tubule	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
CAPN3	muscular-dystrophy/myopathy	calpainopathy/LGMD	protease_sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
COL6A1	muscular-dystrophy/myopathy	collagen VI myopathy	extracellular_matrix	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
COL6A2	muscular-dystrophy/myopathy	collagen VI myopathy	extracellular_matrix	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
COL6A3	muscular-dystrophy/myopathy	collagen VI myopathy	extracellular_matrix	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
CRPPA	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
DNAJB6	muscular-dystrophy/myopathy	LGMD/myofibrillar myopathy	protein_quality_control	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
DYSF	muscular-dystrophy/myopathy	dysferlinopathy/LGMD	membrane_repair	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
FHL1	muscular-dystrophy/myopathy	FHL1 myopathy	sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
FKRP	muscular-dystrophy/myopathy	dystroglycanopathy/LGMD	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
GNE	muscular-dystrophy/myopathy	GNE myopathy	sialic_acid	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
LARGE1	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
LMNA	muscular-dystrophy/myopathy	LMNA-related muscular dystrophy/cardiomyopathy	nuclear_envelope	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
MTM1	muscular-dystrophy/myopathy	myotubular myopathy	phosphoinositide	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
MYH2	muscular-dystrophy/myopathy	myosin myopathy	sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
MYH7	muscular-dystrophy/myopathy	myosin myopathy/cardiomyopathy	sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
NEB	muscular-dystrophy/myopathy	nemaline myopathy	sarcomere	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
POMGNT1	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
POMGNT2	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
POMT1	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.
POMT2	muscular-dystrophy/myopathy	dystroglycanopathy	glycosylation	False	Not available	not_supported_current_atlas	Not supported by the current HepG2 perturbation atlas.	Need disease-relevant external signature or perturbation dataset.

Measurement reliability boundary

Cells estimate target-level deltas; they are not inferential replicates.

Data table: replicate_definition, n_rows, n_targets
replicate_definition	n_rows	n_targets	median_rmse	median_cosine	median_sign_concordance	statistical_unit
cell_split_half	10,800	2,160	0.136	0.331	0.569	target-level replicate delta
batch_split	2,160	2,160	0.137	0.333	0.569	target-level replicate delta
guide_pair	133	133	0.143	0.00605	0.502	target-level replicate delta

Applicability JSON · NMD scope JSON · Global claim boundary

One shared ladder across gene pages and the Workbench

Disease Module Explorer

Coverage by evidence level

What evidence is needed next?