| evidence-finding-1 | KF1: Four public myocardial datasets supplied discovery and external subtype-assignment data. | Article-reported analysis subsets for DCM network taxonomy; no newly recruited clinical cohort | Four public myocardial datasets supplied discovery and external subtype-assignment data. discovery subset: GSE5406: 86 DCM and 16 controls; external subsets: GSE57338: 82/136; GSE116250: 37/14; GSE19303: 40/8 DCM/control samples; reported sample totals: 245 DCM and 174 controls across four datasets; no verified unique-person total | Secondary human myocardial transcriptomics | Article-reported analysis subsets for DCM network taxonomy; no newly recruited clinical cohort | Methods: Data collection and preprocessing (Par6); Results: Cohort characteristics and interactome construction (Par22); Table 1 (Tab1); Figure 2E-G | KF1 |
|---|
| evidence-finding-2 | KF2: Rank-based perturbation features provided a network representation for subtype discovery. | Expression-rank differences were compared with a control-derived reference before feature selection | Rank-based perturbation features provided a network representation for subtype discovery. mapped network: 5,593 nodes and 107,063 edges; selected features: 27,937 discriminative edges; feature-selection rule: intersection of the top 50% of edges for case-control difference and the top 50% for DCM variability | Computational interaction-feature engineering | Expression-rank differences were compared with a control-derived reference before feature selection | Methods: Quantifying gene interactions and Edge perturbation matrix construction (Par8-Par11); Results: Cohort characteristics and interactome construction (Par22) and Edge perturbation profiling (Par24); Figure 1 | KF2 |
|---|
| evidence-finding-3 | KF3: Three network subtypes were recovered and assigned across the discovery and validation datasets. | Retrospective molecular clustering evaluated with UMAP, silhouette analysis and nearest-template prediction | Three network subtypes were recovered and assigned across the discovery and validation datasets. selected cluster count: K = 3; EPS1 range: 43.2-52.5% across analyzed datasets; EPS2 range: 40.0-44.2% across analyzed datasets; EPS3 range: 7.5-13.5% across analyzed datasets | Retrospective clustering and external subtype assignment | Retrospective molecular clustering evaluated with UMAP, silhouette analysis and nearest-template prediction | Methods: Consensus clustering for subtype identification and Validation of clustering stability (Par13-Par14); Results: Consensus clustering identifies three stable DCM subtypes (Par25-Par26); Figure 2A-G | KF3 |
|---|
| evidence-finding-4 | KF4: Coexpression modules and inferred immune patterns differed between the molecular subtypes. | Computational associations in the 74-sample WGCNA subset and gene-expression-based immune profiling; not direct immune-cell counting or causal perturbation | Coexpression modules and inferred immune patterns differed between the molecular subtypes. WGCNA subset and modules: 74 DCM samples after outlier exclusion; 10 modules; EPS1-associated module: 540 genes; module-subtype r = 0.84; EPS2-associated module: 513 genes; module-subtype r = 0.74; EPS3-associated module: 87 genes; module-subtype r = 0.78; interpretation: energy/proteostasis, humoral/platelet-related and respiratory-chain/endocytosis enrichment patterns differed; immune composition was inferred by ssGSEA | Coexpression, enrichment and inferred immune associations | Computational associations in the 74-sample WGCNA subset and gene-expression-based immune profiling; not direct immune-cell counting or causal perturbation | Methods: Identification of subtype-specific gene modules and Immune cell infiltration analysis (Par15-Par17); Results: Subtype-specific co-expression modules (Par28), Functional annotation of molecular subtypes (Par30-Par32), Distinct immune infiltration patterns (Par34); Figures 3-6A-C | KF4 |
|---|
| evidence-finding-5 | KF5: EPS1 showed expression similarity to the IA/IgG responder group in an exploratory retrospective analysis. | Submap compared subtype expression with responder/non-responder profiles in GSE19303; this is not a randomized treatment comparison | EPS1 showed expression similarity to the IA/IgG responder group in an exploratory retrospective analysis. response definition in the source cohort: at least 20% relative LVEF improvement together with at least 5 percentage points absolute improvement; reported expression-matching result: EPS1 association with responder profiles remained significant after Bonferroni correction; an exact corrected P value is not supplied in the Results prose; clinical boundary: no demonstrated benefit of assigning IA/IgG according to EPS subtype | Exploratory retrospective expression-profile matching | Submap compared subtype expression with responder/non-responder profiles in GSE19303; this is not a randomized treatment comparison | Methods: Prediction of IA/IgG therapy sensitivity (Par18); Results: IA/IgG therapy response prediction (Par36); Figure 6D | KF5 |
|---|
| evidence-finding-6 | KF6: A cell stress model reproduced the direction of eight selected EPS1-associated gene-expression differences. | qPCR in angiotensin-II-treated AC16 cells checked genes intersecting EPS1-versus-control and DCM-versus-control contrasts, rather than validating all subtype mechanisms | A cell stress model reproduced the direction of eight selected EPS1-associated gene-expression differences. cell treatment: 10 micromolar angiotensin II for 48 hours; higher-expression genes: 3: ASPN, LUM and NPPA; lower-expression genes: 5: MYOT, FKBP5, SERPINE1, CD163 and ANKRD2; scope: 8 genes; no cell-replicate count or patient-level diagnostic accuracy is inferred | Cell-line qPCR expression-direction check | qPCR in angiotensin-II-treated AC16 cells checked genes intersecting EPS1-versus-control and DCM-versus-control contrasts, rather than validating all subtype mechanisms | Methods: Cell culture and treatment (Par20) and Quantitative real-time PCR analysis (Par19); Results: qPCR confirmation of subtype-specific DEGs (Par37); Figure 7; Discussion: qPCR validation of core subtype genes (Par55) | KF6 |
|---|