{ "contract_schema": "nmd-vcell-perturbation-lab/1.3", "feature_build": "PLAB-20260729-04", "resource_release": "v1.0.0-database-resource", "evidence_freeze": "2026-07-25", "interface_build": "EA-20260729-15", "current_context": "HepG2", "candidate_count": 21, "unordered_candidate_pair_count": 210, "server_rendered_routes": { "single_pattern": "/resource/perturbation/{gene}/", "additive_example": "/resource/perturbation/ZNF133+MON1A/additive/", "default_record": "/resource/perturbation/ZNF133/" }, "capabilities": { "available_now": [ "observed_crispri", "additive_null_hypothesis", "unperturbed_reference_trajectory" ], "unavailable_data_required": [ "knockout", "crispra_or_overexpression", "pair_interaction", "perturbed_fate" ] }, "simulator_levels": [ { "level": "SIM-L0", "capability": "observed_single_crispri", "state": "ACTIVE" }, { "level": "SIM-L1", "capability": "predicted_single_crispri", "state": "LIMITED_STRICT_DIRECT_GATE_UNSUPPORTED" }, { "level": "SIM-L2", "capability": "additive_dual_crispri", "state": "BOUNDED_PREVIEW", "formula": "delta_A_plus_delta_B" }, { "level": "SIM-L3", "capability": "pair_interaction", "state": "LOCKED_NO_OBSERVED_DOUBLE" }, { "level": "SIM-L4", "capability": "knockout_overexpression_context_fate", "state": "LOCKED_DATA_MODALITY_MISSING" } ], "modality_boundaries": { "observed_crispri": "Observed same-HepG2 CRISPRi / knockdown-like evidence.", "predicted_crispri": "Experimental held-out single-perturbation view; strict target-specific predictive support is not established.", "additive_pair": "Descriptive combination of single-gene response programs under delta_AB = delta_A + delta_B; gamma_AB is omitted.", "knockout": "Locked: CRISPRi is not a complete knockout.", "overexpression": "Locked: GSE133344 provides cross-cell-line CRISPRa and combination method calibration, but no matched candidate activation response in muscle or DMD.", "trajectory": "Reference available: GSE52529 supplies an unperturbed human-myogenic 0/24/48/72-hour trajectory. Perturbation-conditioned velocity and fate remain locked." }, "pathway_program_panels": [ { "program_id": "myogenic_contractile", "label": "Myogenic / contractile", "color": "teal", "genes": [ "ACTA1", "ACTN2", "CAV3", "CKM", "DES", "MEF2C", "MYH1", "MYH2", "MYH3", "MYH7", "MYLPF", "MYOD1", "MYOG", "NCAM1", "PAX7", "TNNC1", "TNNC2" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." }, { "program_id": "ecm_fibrotic", "label": "ECM / fibrotic", "color": "amber", "genes": [ "COL1A1", "COL1A2", "COL3A1", "COL6A1", "COL6A2", "COL6A3", "COMP", "CTHRC1", "DCN", "FN1", "LUM", "MMP2", "MMP9", "SPP1", "TGFBI", "TIMP1" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." }, { "program_id": "inflammatory_stress", "label": "Inflammatory / stress", "color": "coral", "genes": [ "C3", "DDIT4", "HSPA1A", "IFI30", "IFIT1", "IFITM3", "IL6", "IRF1", "ISG15", "LITAF", "PYCARD", "SERPINA1", "SERPINA3", "SOD2", "STAT1" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." }, { "program_id": "cell_cycle", "label": "Cell cycle / proliferation", "color": "violet", "genes": [ "BIRC5", "CCNB1", "CDC20", "CDK1", "CENPF", "MKI67", "PTTG1", "STMN1", "TOP2A", "TUBA1B", "TUBB" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." }, { "program_id": "metabolic_secretory", "label": "Metabolic / secretory", "color": "blue", "genes": [ "ALB", "ANGPTL8", "APOA1", "APOA2", "APOE", "FABP3", "FDFT1", "GPX3", "IGFBP1", "MLXIPL", "RBP4" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." }, { "program_id": "proteostasis_membrane", "label": "Proteostasis / membrane", "color": "slate", "genes": [ "CALR", "CAV3", "DDIT4", "DYSF", "GPX3", "HSP90AA1", "HSPA1A", "HSPB1", "LAMP1", "SGCA", "SGCB", "VCP" ], "interpretation": "Descriptive overlap against a frozen, project-curated gene panel; not a formal enrichment test, mechanism claim or pathway activity estimate." } ], "external_evidence_registry": { "contract_schema": "nmd-vcell-external-perturbation-evidence/1.1", "feature_build": "EXT-PERT-20260729-02", "datasets": [ { "accession": "GSE293514", "title": "Human myoblast fusion CRISPR screen and single-cell CRISPR/RNA-seq", "evidence_role": "external_human_myoblast_context_and_fusion_safety_screen", "qualification_state": "QUALIFIED_BOUNDED_CONTEXT", "direct_validation_of_current_21_candidates": false, "limitations": [ "healthy-donor myoblast context rather than DMD", "fusion endpoint does not cover all neuromuscular mechanisms", "processed single-cell guide assignment is not fully reconstructable from deposited sidecars" ], "source_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293514", "selected_candidate_summary": { "candidate_count": 21, "in_myo_crispr_library": 9, "not_in_myo_crispr_library": 12, "fusion_hits_fdr_lt_0_1": 0, "individually_validated_hits": 0 } }, { "accession": "GSE272233", "title": "CRISPR correction of DMD exon duplications in patient-derived myogenic cells", "evidence_role": "orthogonal_dmd_crispr_correction_transcriptome_reference", "qualification_state": "QUALIFIED_ORTHOGONAL_REFERENCE", "sample_count": 21, "biological_replicates_per_group": 3, "mutation_contexts": [ "duplication_exon_2", "duplication_exons_2_9", "duplication_exons_8_9" ], "direct_validation_of_current_21_candidates": false, "limitations": [ "bulk RNA-seq rather than single-cell perturbation", "candidate genes were not themselves perturbed", "wild-type comparator is not isogenic", "corrected clones may retain clone-specific effects" ], "source_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272233" }, { "accession": "GSE52529", "title": "Single-cell trajectory reconstruction of human skeletal myoblast differentiation", "evidence_role": "time_anchored_human_myogenic_trajectory_reference", "qualification_state": "QUALIFIED_REFERENCE_ONLY", "cell_count": 271, "physical_timepoints_hours": [ 0, 24, 48, 72 ], "direct_validation_of_current_21_candidates": false, "perturbation_conditioned_trajectory": false, "limitations": [ "unperturbed differentiation reference rather than candidate perturbation", "published pseudotime is descriptive and does not establish causal fate control", "healthy primary myoblast context rather than DMD" ], "source_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52529", "package_url": "https://bioconductor.org/packages/release/data/experiment/html/HSMMSingleCell.html" }, { "accession": "GSE133344", "title": "Mapping cellular behavior with combinatorial CRISPRa perturbations", "evidence_role": "cross_cell_line_crispra_and_combination_method_calibration", "qualification_state": "QUALIFIED_METHOD_CALIBRATION_ONLY", "cell_line": "K562", "reported_perturbations": 287, "reported_single_target_gene_set": 112, "direct_validation_of_current_21_candidates": false, "limitations": [ "K562 rather than muscle or DMD context", "current local compact asset contains expression features, not guide identities", "candidate feature presence does not mean the candidate was a CRISPRa target" ], "source_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133344", "paper_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6746554/" } ], "gse293514_selected_candidate_summary": { "candidate_count": 21, "in_myo_crispr_library": 9, "not_in_myo_crispr_library": 12, "fusion_hits_fdr_lt_0_1": 0, "individually_validated_hits": 0 }, "gse272233_qc": { "raw_gene_rows": 62757, "aggregated_gene_symbols": 62710, "genes_retained_filter_by_expr": 22230, "sample_count": 21, "groups": { "WT": 3, "Dup2": 3, "Dup2_corrected": 3, "Dup2_9": 3, "Dup2_9_corrected": 3, "Dup8_9": 3, "Dup8_9_corrected": 3 } }, "gse272233_contrast_summary": [ { "contrast": "dup2_correction", "tested_genes": 22230, "fdr_lt_0_05": 2812, "fdr_lt_0_05_abs_logfc_ge_1": 1090, "up_fdr_lt_0_05": 1125, "down_fdr_lt_0_05": 1687 }, { "contrast": "dup2_9_correction", "tested_genes": 22230, "fdr_lt_0_05": 375, "fdr_lt_0_05_abs_logfc_ge_1": 167, "up_fdr_lt_0_05": 154, "down_fdr_lt_0_05": 221 }, { "contrast": "dup8_9_correction", "tested_genes": 22230, "fdr_lt_0_05": 2736, "fdr_lt_0_05_abs_logfc_ge_1": 979, "up_fdr_lt_0_05": 1498, "down_fdr_lt_0_05": 1238 } ], "gse52529_qc": { "feature_rows": 47192, "representative_gene_symbols": 46992, "cell_count": 271, "cells_by_physical_timepoint": { "0": 69, "24": 74, "48": 79, "72": 49 }, "cells_by_published_state": { "1": 99, "2": 129, "3": 43 }, "pseudotime_min": 0, "pseudotime_median": 45.04439887, "pseudotime_max": 76.65415946, "candidate_genes_measured": 20, "candidate_genes_total": 21 }, "gse133344_feature_qc": { "expression_features": 33694, "current_candidates_present_as_expression_features": 20, "current_candidate_total": 21, "current_candidates_absent_as_expression_features": "INTS13" }, "claim_boundary": "GSE293514 is a bounded human-myoblast fusion screen; GSE272233 is an orthogonal DMD-correction transcriptome reference; GSE52529 is an unperturbed, time-anchored myogenic trajectory reference; and GSE133344 is cross-cell-line CRISPRa/combination method calibration. None supplies direct independent DMD perturbation validation for the current 21 candidates, observed candidate-pair interactions, candidate overexpression responses in muscle, or perturbation-conditioned fate.", "api": "api/v1.1/external_perturbation_evidence.json" }, "candidates": [ { "gene": "ADAM10", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 161, "observed_counteralignment": 0.016577908426075, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.3990233540534973 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 3.1162, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": -0.075195, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 8.52768073, "correction_effects": { "dup2": { "logfc": 0.34502215, "fdr": 0.02082656 }, "dup2_9": { "logfc": 0.14643984, "fdr": 0.5478339 }, "dup8_9": { "logfc": 0.16224166, "fdr": 0.32438886 } }, "significant_correction_contrasts_fdr_0_05": 1, "exploratory_reversal_contrasts_fdr_0_05": 1, "correction_direction_state": "consistent_up_when_significant", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.97785978, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 0.51360317, "pseudotime_spearman_rho": 0.10573881, "pseudotime_spearman_fdr_among_21_candidates": 0.19545648, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.02824511, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 19.79135986, "median_fpkm": 15.3611, "mean_log1p_fpkm": 2.70495072 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 42.9995621, "median_fpkm": 26.7802, "mean_log1p_fpkm": 3.13894598 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 41.50407899, "median_fpkm": 30.1722, "mean_log1p_fpkm": 3.13697187 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 28.29712898, "median_fpkm": 18.0358, "mean_log1p_fpkm": 2.87821727 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 2.79057486 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 2.72814578 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 2.72916878 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 3.35355625 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 3.18906 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 3.17212527 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 3.06039478 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 2.39226087 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 3.10458352 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 3.27644761 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "SERPINA3", "SERPINE1", "MKI67", "KRT18", "ACTA1", "DDIT4", "SERPINA1", "STMN1", "MT2A", "PYCARD", "SCN9A", "MATN3" ], "disease_like": [ "DLK1", "CTHRC1", "APOA1", "COMP", "PLA2G2A", "TSPAN8", "GPX3", "CTNNAL1", "CLU", "SOD2", "TNFRSF12A", "HMGB2" ], "observed_aligned": [ "TUBA1B", "S100A11", "HMGB2", "S100P", "MALAT1", "PCNA", "KRT19", "HMGN2", "DST", "DEK", "ODC1", "TUBB2B" ], "observed_opposed": [ "TTR", "VTN", "SERPINA6", "TUBB4B", "ERRFI1", "FGB", "TAGLN", "PLIN2", "MYL9", "JUN", "APOM", "FGG" ], "largest_model_errors": [ "TTR", "TUBA1B", "VTN", "SPP1", "SERPINA3", "FGB", "HMGA1", "PLIN2", "LGALS2", "TUBB2A", "MYL9", "C5" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "CALR", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 86, "observed_counteralignment": 0.0342720008433927, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.1070653423666954 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 88.6307, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": -0.065853, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 8.19937769, "correction_effects": { "dup2": { "logfc": -0.42896174, "fdr": 0.0082007 }, "dup2_9": { "logfc": -0.01033944, "fdr": 0.98442435 }, "dup8_9": { "logfc": 0.23596725, "fdr": 0.16220968 } }, "significant_correction_contrasts_fdr_0_05": 1, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "consistent_down_when_significant", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 1, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.57455099, "pseudotime_spearman_rho": 0.08676531, "pseudotime_spearman_fdr_among_21_candidates": 0.24434664, "physical_time_kruskal_wallis_fdr_among_21_candidates": 1.96730949e-7, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 132.54667754, "median_fpkm": 128.54, "mean_log1p_fpkm": 4.80985077 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 152.82966351, "median_fpkm": 138.737, "mean_log1p_fpkm": 4.88525422 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 156.00769494, "median_fpkm": 140.007, "mean_log1p_fpkm": 4.9117559 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 88.97160816, "median_fpkm": 72.9151, "mean_log1p_fpkm": 4.30858799 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 4.75490627 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 4.70426011 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 4.77381639 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 4.82936568 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 4.56547027 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 4.83886601 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 4.84689706 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 4.5261103 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 4.81787166 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 5.02799366 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "APOA1", "MATN3", "MT2A", "MKI67", "GPX3", "PYCARD", "SOD2", "CRYAB", "CDT1", "CTNNAL1", "SYNE1", "CFB" ], "disease_like": [ "DLK1", "SERPINA3", "CTHRC1", "PLA2G2A", "COMP", "ACTA1", "SPP1", "TSPAN8", "S100A2", "HSPA1A", "MLXIPL", "HMGB2" ], "observed_aligned": [ "CALR", "IGFBP1", "HMGB2", "IFITM3", "SAT1", "CENPF", "FABP1", "MKI67", "SNX6", "ORM2", "HMGCS1", "ANGPTL8" ], "observed_opposed": [ "DHRS2", "HIST1H4C", "PLIN2", "FGA", "CCN2", "FOXQ1", "MATN3", "FGB", "ERRFI1", "NPW", "IER3", "SERPINA3" ], "largest_model_errors": [ "CALR", "DHRS2", "SNX6", "SDF2L1", "HSP90B1", "MANF", "NPW", "HSPA5", "CCL20", "HIST1H4C", "ANGPTL8", "DEFB1" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "CPEB1", "current_action": "verify_expression", "current_display_label": "Verify expression", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 100, "observed_counteralignment": 0.0118224730803746, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.8501244187355042 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.6666666666666666, "assessed_sources": 3 }, "muscle_context": { "skeletal_muscle_median_tpm": 0.731389, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 1.05532863, "correction_effects": { "dup2": { "logfc": -0.94693216, "fdr": 0.01005329 }, "dup2_9": { "logfc": 0.58998749, "fdr": 0.32772329 }, "dup8_9": { "logfc": -0.22296312, "fdr": 0.66510356 } }, "significant_correction_contrasts_fdr_0_05": 1, "exploratory_reversal_contrasts_fdr_0_05": 1, "correction_direction_state": "consistent_down_when_significant", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.05904059, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.91154148, "pseudotime_spearman_rho": -0.02239986, "pseudotime_spearman_fdr_among_21_candidates": 0.84734303, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.27414853, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0.42011116, "median_fpkm": 0, "mean_log1p_fpkm": 0.09410543 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0.0572723, "median_fpkm": 0, "mean_log1p_fpkm": 0.03005448 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0.03285971, "median_fpkm": 0, "mean_log1p_fpkm": 0.01880874 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0.17649982, "median_fpkm": 0, "mean_log1p_fpkm": 0.06432559 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.16934294 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.00295131 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.07813727 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.03041963 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.16900316 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.00570472 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.00629358 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.03161179 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "DLK1", "PLA2G2A", "MKI67", "APOA1", "SPP1", "CDT1", "STMN1", "SERPINE1", "CTHRC1", "ACTA1", "MT2A", "CTNNAL1" ], "disease_like": [ "TSPAN8", "SERPINA3", "C3", "APOE", "COMP", "SERPINA1", "HMGB2", "MLXIPL", "CSRP2", "HSPA1A", "TNFRSF12A", "PLTP" ], "observed_aligned": [ "TUBA1B", "H2AFZ", "STMN1", "NEAT1", "HMGB2", "TUBB", "CENPF", "HIST1H4C", "A2M", "CYGB", "S100A6", "PCLAF" ], "observed_opposed": [ "GAS5", "ZFAS1", "SNHG8", "FLNA", "TUBB3", "HSPA1A", "SEL1L", "MAGED2", "ANXA4", "DKK1", "STC2", "HMGCS1" ], "largest_model_errors": [ "MDM2", "TUBB", "TUBA1B", "H2AFZ", "SAA4", "NEAT1", "A2M", "FDXR", "STMN1", "CYGB", "S100A6", "HMGB2" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "DDX19B", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 145, "observed_counteralignment": 0.0181322540721587, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.1254798173904419 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 2 }, "muscle_context": { "skeletal_muscle_median_tpm": 7.22865, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": 0.069099, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 4.01880946, "correction_effects": { "dup2": { "logfc": -0.16249822, "fdr": 0.40020702 }, "dup2_9": { "logfc": -0.28941549, "fdr": 0.24582336 }, "dup8_9": { "logfc": -0.19440813, "fdr": 0.30635495 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.56457565, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.57097177, "pseudotime_spearman_rho": -0.09632341, "pseudotime_spearman_fdr_among_21_candidates": 0.21591921, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.2592999, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 13.66222875, "median_fpkm": 3.10425, "mean_log1p_fpkm": 1.58355623 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 9.53733336, "median_fpkm": 0.093354, "mean_log1p_fpkm": 1.02743076 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 10.95984343, "median_fpkm": 0.314919, "mean_log1p_fpkm": 1.14512394 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 9.16422604, "median_fpkm": 0.886717, "mean_log1p_fpkm": 1.25504107 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 1.47202823 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 1.79839453 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 1.29458891 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 1.26655129 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 1.55392776 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.68134293 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.85428533 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 1.23034735 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 1.14573639 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 1.15116378 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "SERPINA3", "C3", "KRT18", "MLXIPL", "GPX3", "TSPAN8", "LITAF", "SERPINA1", "AK1", "EPB41L1", "APOE", "DDIT4" ], "disease_like": [ "DLK1", "PLA2G2A", "CTHRC1", "MKI67", "MATN3", "COMP", "S100A2", "SOD2", "IFI30", "HSPA1A", "STMN1", "SERPINE1" ], "observed_aligned": [ "IGFBP1", "CKS2", "MCM7", "STMN1", "TTR", "MKI67", "TUBB4B", "PCLAF", "C3", "CKS1B", "CCNB1", "IDI1" ], "observed_opposed": [ "BPIFB2", "GDF15", "SERPINA3", "NEDD9", "KLF6", "MATN3", "AFP", "VTN", "ANKRD1", "FOXQ1", "INSIG2", "BIRC5" ], "largest_model_errors": [ "BPIFB2", "GDF15", "NFKBIA", "SERPINA3", "NEDD9", "KLF6", "MATN3", "VTN", "AFP", "BIRC5", "FBXO2", "NUDT8" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "DNAAF3", "current_action": "verify_expression", "current_display_label": "Verify expression", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 115, "observed_counteralignment": 0.0344381820755609, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.0370117537677288 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "source_limited", "source_direction_agreement": 1, "assessed_sources": 1 }, "muscle_context": { "skeletal_muscle_median_tpm": 0.0755557, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": -1.69156951, "correction_effects": { "dup2": { "logfc": -0.23027013, "fdr": 0.78683638 }, "dup2_9": { "logfc": -0.15010408, "fdr": 0.95519715 }, "dup8_9": { "logfc": -0.8584961, "fdr": 0.35018444 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.00369004, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -2.33776486, "pseudotime_spearman_rho": -0.09257407, "pseudotime_spearman_fdr_among_21_candidates": 0.22189389, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.4253183, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0.40551884, "median_fpkm": 0, "mean_log1p_fpkm": 0.04879179 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.12469013 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "APOA1", "TSPAN8", "CTHRC1", "ACTA1", "C5", "GPX3", "IGF2", "CLU", "MLXIPL", "CTNNAL1", "TNFRSF12A", "DDIT4" ], "disease_like": [ "DLK1", "PLA2G2A", "SERPINA3", "COMP", "C3", "SERPINA1", "RARRES2", "HSPA1A", "IFI30", "MKI67", "FST", "SERPINE1" ], "observed_aligned": [ "AFP", "MARCKS", "ALB", "DHRS2", "A2M", "SERPINA7", "TYMS", "PHLDA3", "ASCC3", "FAM162A", "HSPA5", "FAM50A" ], "observed_opposed": [ "TAGLN", "GPC3", "LCN15", "TNFRSF12A", "DLK1", "ACSL3", "S100A4", "DEFB1", "PLA2G2A", "IL32", "APOA1", "IGFBP1" ], "largest_model_errors": [ "MARCKS", "SLC13A5", "TAGLN", "GPC3", "IGFBP1", "LCN15", "TNFRSF12A", "S100A4", "IL32", "ALDH1A1", "ACSL3", "PLA2G2A" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "DNM1", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 116, "observed_counteralignment": 0.0023798166472955, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.2550452351570129 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 1.39988, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": -1.54084661, "correction_effects": { "dup2": { "logfc": -0.4950344, "fdr": 0.72145172 }, "dup2_9": { "logfc": 1.19036839, "fdr": 0.49654474 }, "dup8_9": { "logfc": 0.00393384, "fdr": 0.99845066 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.09594096, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 0.6269278, "pseudotime_spearman_rho": -0.00405565, "pseudotime_spearman_fdr_among_21_candidates": 0.98808617, "physical_time_kruskal_wallis_fdr_among_21_candidates": 9.82038877e-7, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0.00119026, "median_fpkm": 0, "mean_log1p_fpkm": 0.00114391 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0.15888791, "median_fpkm": 0, "mean_log1p_fpkm": 0.05942777 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0.10138777, "median_fpkm": 0, "mean_log1p_fpkm": 0.05331307 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0.05626539, "median_fpkm": 0, "mean_log1p_fpkm": 0.05087618 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.01413386 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.00389097 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.00484822 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.04651083 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.12675349 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.08193478 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.02906096 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.10175461 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.00504577 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "DLK1", "PLA2G2A", "MKI67", "SERPINE1", "STMN1", "CDT1", "SPP1", "APOA1", "ACTA1", "MLXIPL", "MATN3", "MT2A" ], "disease_like": [ "SERPINA3", "TSPAN8", "CTHRC1", "APOE", "C3", "COMP", "HSPA1A", "HMGB2", "PLTP", "SERPINA1", "GPX3", "SORL1" ], "observed_aligned": [ "TAGLN", "KPNA2", "SPTSSA", "CDK1", "LMNB1", "PRR11", "CENPF", "GLUD1", "RHOBTB3", "PCLAF", "TOP2A", "HSPA8" ], "observed_opposed": [ "IGFBP1", "NEAT1", "MALAT1", "TUBA1B", "LGALS3", "PTTG1", "ANGPTL8", "H2AFZ", "S100P", "C3", "STMN1", "SAA4" ], "largest_model_errors": [ "IGFBP1", "NEAT1", "TUBA1B", "LGALS3", "MALAT1", "H2AFZ", "STMN1", "PTTG1", "ALB", "ANGPTL8", "C3", "S100P" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "EHMT2", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 101, "observed_counteralignment": 0.0298003663560908, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.0329451151192188 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 6.40587, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 3.99795178, "correction_effects": { "dup2": { "logfc": 0.20451853, "fdr": 0.24694616 }, "dup2_9": { "logfc": -0.07007108, "fdr": 0.84707042 }, "dup8_9": { "logfc": 0.02993864, "fdr": 0.91043887 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.54612546, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.25131168, "pseudotime_spearman_rho": -0.00091129, "pseudotime_spearman_fdr_among_21_candidates": 0.98808617, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.00003405, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 5.4572273, "median_fpkm": 0.0932865, "mean_log1p_fpkm": 0.8301313 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 4.24857966, "median_fpkm": 0, "mean_log1p_fpkm": 0.62828076 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 6.91205697, "median_fpkm": 0, "mean_log1p_fpkm": 0.72740537 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 4.56880576, "median_fpkm": 1.00165, "mean_log1p_fpkm": 1.066764 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.74827804 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.67111338 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 1.01734772 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.91853953 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.96231531 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.6407299 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.73611342 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.5721616 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.69639157 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.91098406 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; 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Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "EPS8L1", "current_action": "verify_expression", "current_display_label": "Verify expression", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 269, "observed_counteralignment": 0.0035653885102933, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.0973614528775215 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "multisource_direction_consistent", "source_direction_agreement": 1, "assessed_sources": 2 }, "muscle_context": { "skeletal_muscle_median_tpm": 0.236384, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; 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Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "GFOD2", "current_action": "hold_pending_external_audit", "current_display_label": "Provisional hold · external report not yet audited", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 127, "observed_counteralignment": 0.0741134084110689, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.0368111878633499 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 2.94732, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 3.41928109, "correction_effects": { "dup2": { "logfc": -0.26365887, "fdr": 0.1897428 }, "dup2_9": { "logfc": -0.16652531, "fdr": 0.62370287 }, "dup8_9": { "logfc": 0.00365379, "fdr": 0.98940775 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.29889299, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 0.78197837, "pseudotime_spearman_rho": -0.055672, "pseudotime_spearman_fdr_among_21_candidates": 0.52800924, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.00000145715196, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 1.60346549, "median_fpkm": 0, "mean_log1p_fpkm": 0.39689095 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 1.45647555, "median_fpkm": 0, "mean_log1p_fpkm": 0.25593139 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 4.17703739, "median_fpkm": 0, "mean_log1p_fpkm": 0.42009395 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 2.82908709, "median_fpkm": 0.345698, "mean_log1p_fpkm": 0.66420691 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.52330282 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.5023675 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.36262099 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.56114897 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.43027109 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.09847926 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.77002485 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.49391383 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.27782881 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.12568177 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "SERPINA3", "SPP1", "MLXIPL", "DDIT4", "KRT18", "EPB41L1", "MKI67", "RARRES2", "GPX3", "LITAF", "SERPINA1", "PYCARD" ], "disease_like": [ "DLK1", "PLA2G2A", "CTHRC1", "COMP", "CTNNAL1", "HSPA1A", "SOD2", "S100A2", "SCN9A", "APOE", "HMGB2", "IFI30" ], "observed_aligned": [ "APOA2", "LYZ", "RNASET2", "APOH", "TF", "ITIH2", "H1FX", "H1F0", "NEDD9", "TFPI", "IFITM3", "IER3" ], "observed_opposed": [ "FBXO2", "IGFBP1", "ANGPTL8", "HMGB2", "CENPF", "DLK1", "TAGLN", "MKI67", "SAT2", "IFNGR1", "RBP4", "PTMA" ], "largest_model_errors": [ "FBXO2", "C3", "LYZ", "RBP4", "MKI67", "ORM1", "RNASET2", "IGFBP1", "DLK1", "APOH", "ANGPTL8", "CENPF" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "INTS13", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 157, "observed_counteralignment": 0.0192678440828641, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.2944151163101196 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "exploratory_multisource_core", "source_direction_agreement": 1, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 10.9911, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 4.676713, "correction_effects": { "dup2": { "logfc": -0.25535064, "fdr": 0.05991596 }, "dup2_9": { "logfc": -0.01431687, "fdr": 0.97068432 }, "dup8_9": { "logfc": -0.30601963, "fdr": 0.02491036 } }, "significant_correction_contrasts_fdr_0_05": 1, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "consistent_down_when_significant", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": false, "detected_fraction_gt_0": null, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": null, "pseudotime_spearman_rho": null, "pseudotime_spearman_fdr_among_21_candidates": null, "physical_time_kruskal_wallis_fdr_among_21_candidates": null, "time_profile": [], "pseudotime_profile": [], "perturbation_conditioned": false, "interpretation": "Gene symbol was not present in the curated HSMMSingleCell annotation; no trajectory reference is emitted." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": false, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "TSPAN8", "APOE", "SERPINA1", "HMGB2", "C3", "KRT18", "AK1", "DDIT4", "SCN9A", "TNFRSF12A", "PYCARD", "MATN3" ], "disease_like": [ "DLK1", "MKI67", "PLA2G2A", "CTHRC1", "SERPINE1", "STMN1", "CDT1", "HSPA1A", "APOA1", "SOD2", "CTNNAL1", "GPX3" ], "observed_aligned": [ "NEAT1", "H2AFZ", "ANP32E", "AKR1C1", "MALAT1", "FTL", "CCDC85B", "TUBB", "ID2", "TK1", "ACTA2", "PHGDH" ], "observed_opposed": [ "IGFBP1", "SERPINE1", "S100A11", "VTN", "TTR", "ALB", "APOM", "IL32", "SAT1", "GDF15", "SPOCK2", "ASPSCR1" ], "largest_model_errors": [ "IGFBP1", "LYZ", "SERPINE1", "S100A11", "APOM", "ALB", "TTR", "VTN", "G6PD", "A2M", "SPOCK2", "IL32" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "LMO2", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 96, "observed_counteralignment": 0.0072367047585843, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.0498822554945945 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 15.237, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 0.27828039, "correction_effects": { "dup2": { "logfc": -0.98148905, "fdr": 0.07112593 }, "dup2_9": { "logfc": -0.80318856, "fdr": 0.4273561 }, "dup8_9": { "logfc": -1.22445994, "fdr": 0.0147092 } }, "significant_correction_contrasts_fdr_0_05": 1, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "consistent_down_when_significant", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.00369004, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.42125589, "pseudotime_spearman_rho": -0.09724167, "pseudotime_spearman_fdr_among_21_candidates": 0.21591921, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.4253183, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0.03390928, "median_fpkm": 0, "mean_log1p_fpkm": 0.01747671 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.0446627 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "PLA2G2A", "APOA1", "CTHRC1", "CTNNAL1", "MKI67", "SOD2", "GPX3", "STMN1", "DLK1", "CDT1", "SERPINE1", "PYCARD" ], "disease_like": [ "SERPINA3", "SPP1", "SERPINA1", "CSRP2", "C3", "HMGB2", "APOE", "MLXIPL", "EPB41L1", "TSPAN8", "KRT18", "HSPH1" ], "observed_aligned": [ "TTR", "HIST1H4C", "ASPSCR1", "A2M", "PCSK1N", "GADD45A", "HSPB1", "APOB", "KLF6", "DBN1", "RBP4", "NKD1" ], "observed_opposed": [ "IGFBP1", "STMN1", "CENPF", "HMGN2", "RRM2", "H2AFZ", "PCNA", "CENPW", "PTTG1", "AKR1C3", "S100A4", "S100A14" ], "largest_model_errors": [ "IGFBP1", "STMN1", "S100A4", "CENPF", "HMGN2", "PCNA", "S100A14", "H2AFZ", "DHRS2", "SERPINA3", "RRM2", "ANGPTL8" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "MON1A", "current_action": "muscle_assay", "current_display_label": "Muscle-context assay", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 94, "observed_counteralignment": 0.0465108672448511, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.2672851085662842 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 8.05698, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": -0.10707, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 2.974323, "correction_effects": { "dup2": { "logfc": -0.13835549, "fdr": 0.58692601 }, "dup2_9": { "logfc": -0.20633493, "fdr": 0.56792726 }, "dup8_9": { "logfc": -0.40090832, "fdr": 0.06930161 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.21402214, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 0.45349461, "pseudotime_spearman_rho": -0.01860229, "pseudotime_spearman_fdr_among_21_candidates": 0.84995451, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.33855573, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 2.01348628, "median_fpkm": 0, "mean_log1p_fpkm": 0.34521114 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 1.77436673, "median_fpkm": 0, "mean_log1p_fpkm": 0.16653842 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0.66400578, "median_fpkm": 0, "mean_log1p_fpkm": 0.21166557 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 2.79410918, "median_fpkm": 0, "mean_log1p_fpkm": 0.5118543 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.57502389 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.02800953 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.42735991 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.36403418 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.43967946 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.21211118 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.27034135 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.28961351 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.19199914 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.08554303 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "DLK1", "MATN3", "MKI67", "EPB41L1", "APOA1", "SERPINE1", "CDT1", "MT2A", "JUP", "RASD1", "ACTA1", "CLU" ], "disease_like": [ "PLA2G2A", "CTHRC1", "TSPAN8", "C3", "COMP", "HSPA1A", "SORL1", "APOE", "HMGB2", "CSRP2", "TNFRSF12A", "CTNNAL1" ], "observed_aligned": [ "LYZ", "IGFBP1", "CRIP1", "GRN", "AMBP", "SOX4", "GOT1", "MT2A", "CP", "MGST1", "NEU4", "TAGLN" ], "observed_opposed": [ "AKR1C1", "TUBA1B", "HMGB2", "ANGPTL8", "NEAT1", "MKI67", "HMGN2", "BIRC5", "TOP2A", "GINS2", "TPX2", "TUBB4B" ], "largest_model_errors": [ "AKR1C1", "TUBA1B", "MKI67", "TOP2A", "ANGPTL8", "HMGB2", "NEAT1", "TSPYL1", "BIRC5", "LCN15", "HMGN2", "UBE2C" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "MPHOSPH6", "current_action": "computational_replication", "current_display_label": "Computational replication", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 83, "observed_counteralignment": 0.0156264944854757, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.5218862295150757 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "exploratory_multisource_core", "source_direction_agreement": 1, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 4.94586, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": 0.37153, "fusion_pos_fdr": 0.77869, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 3.22524103, "correction_effects": { "dup2": { "logfc": -0.00892899, "fdr": 0.98072645 }, "dup2_9": { "logfc": -0.04867437, "fdr": 0.92657792 }, "dup8_9": { "logfc": -0.30458736, "fdr": 0.15992667 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.70479705, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.45542811, "pseudotime_spearman_rho": -0.12193511, "pseudotime_spearman_fdr_among_21_candidates": 0.14220831, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.27414853, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 30.82872803, "median_fpkm": 20.8343, "mean_log1p_fpkm": 2.57249316 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 33.27023207, "median_fpkm": 5.836225, "mean_log1p_fpkm": 2.07710354 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 26.98410615, "median_fpkm": 2.89955, "mean_log1p_fpkm": 1.89109175 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 22.45612735, "median_fpkm": 9.82138, "mean_log1p_fpkm": 2.08796072 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 3.08990516 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 2.73017709 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 2.15072028 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 2.21301992 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 1.81381275 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 1.35701387 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 1.6531733 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 2.25554566 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 1.71237936 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 2.5203155 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "PLA2G2A", "MKI67", "STMN1", "SPP1", "KRT18", "MT2A", "CDT1", "SERPINE1", "MATN3", "CKB", "RARRES2", "PYCARD" ], "disease_like": [ "DLK1", "SERPINA3", "APOA1", "COMP", "HMGB2", "APOE", "S100A2", "GPX3", "CSRP2", "HSPA1A", "AK1", "IFI30" ], "observed_aligned": [ "TUBA1B", "STMN1", "HMGB2", "CENPF", "H2AFZ", "PCLAF", "TUBB", "NASP", "HIST1H4C", "GDF15", "MALAT1", "TPX2" ], "observed_opposed": [ "KRT19", "LCN15", "S100A4", "KRT8", "DCDC2", "AFP", "DEFB1", "FGB", "APOA1", "STARD10", "TPM1", "ITIH2" ], "largest_model_errors": [ "MDM2", "NEAT1", "S100A6", "CYGB", "KRT19", "DEFB1", "FDXR", "CDKN1A", "LCN15", "ID2", "H2AFZ", "STMN1" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "NAGLU", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 88, "observed_counteralignment": 0.011015441933206, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.0082676243036985 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 8.66362, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": 0.061132, "fusion_pos_fdr": 0.685034, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 3.7992606, "correction_effects": { "dup2": { "logfc": -0.09252269, "fdr": 0.72054461 }, "dup2_9": { "logfc": -0.24794554, "fdr": 0.41269803 }, "dup8_9": { "logfc": 0.03135597, "fdr": 0.9216087 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.15498155, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.00488155, "pseudotime_spearman_rho": 0.02909939, "pseudotime_spearman_fdr_among_21_candidates": 0.80232802, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.60779782, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0.81778426, "median_fpkm": 0, "mean_log1p_fpkm": 0.19730024 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0.38778793, "median_fpkm": 0, "mean_log1p_fpkm": 0.14418266 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 1.58692284, "median_fpkm": 0, "mean_log1p_fpkm": 0.29375321 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0.81468406, "median_fpkm": 0, "mean_log1p_fpkm": 0.17609166 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.10701441 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.175253 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.21042623 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.20497936 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.21189825 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.17996016 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.08309807 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.33336709 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.26038593 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.30092504 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "APOA1", "MKI67", "MLXIPL", "EPB41L1", "STMN1", "SERPINE1", "MATN3", "CDT1", "PLA2G2A", "PLLP", "CTHRC1", "GSN" ], "disease_like": [ "DLK1", "SERPINA3", "C3", "APOE", "COMP", "HMGB2", "SERPINA1", "PLTP", "AK1", "TNFRSF12A", "PYCARD", "CD9" ], "observed_aligned": [ "TUBA1B", "S100A6", "TUBA1C", "KRT19", "NEAT1", "FBXO2", "PTTG1", "FDXR", "APOH", "DDX39A", "CDIP1", "MCM3" ], "observed_opposed": [ "ANGPTL8", "IGFBP1", "ALB", "TTR", "SPTBN1", "SERPINA1", "MATN3", "MYBL2", "DUT", "SERPINA3", "SERPINE1", "MKI67" ], "largest_model_errors": [ "ALB", "ANGPTL8", "HMGB2", "STMN1", "IGFBP1", "TTR", "RBP4", "MKI67", "SPTBN1", "SERPINA1", "SERPINA3", "MATN3" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "RAC3", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 92, "observed_counteralignment": 0.0247824419731771, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.4650355875492096 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 0.339463, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": -0.23989122, "correction_effects": { "dup2": { "logfc": -0.39371699, "fdr": 0.60497002 }, "dup2_9": { "logfc": -0.27518952, "fdr": 0.83521397 }, "dup8_9": { "logfc": 0.74679524, "fdr": 0.34648736 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 0, "pseudotime_spearman_rho": 0, "pseudotime_spearman_fdr_among_21_candidates": 0, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 0, "median_fpkm": 0, "mean_log1p_fpkm": 0 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "DLK1", "APOA1", "MKI67", "MLXIPL", "STMN1", "SERPINE1", "CDT1", "MT2A", "C5", "KRT18", "EPB41L1", "CTNNAL1" ], "disease_like": [ "SERPINA3", "PLA2G2A", "APOE", "C3", "SERPINA1", "HMGB2", "TSPAN8", "COMP", "HSPA1A", "CSRP2", "C2", "SPP1" ], "observed_aligned": [ "STMN1", "H2AFZ", "IGFBP1", "NEAT1", "A2M", "HMGB2", "SLC2A3", "HMGB1", "CENPF", "HSP90AA1", "TUBA1B", "MCM3" ], "observed_opposed": [ "HSPA5", "AKR1C3", "DEFB1", "APOA2", "SDF2L1", "SPP1", "SERPINA3", "FDXR", "APOE", "C4BPB", "HSP90B1", "RSRP1" ], "largest_model_errors": [ "HSPA5", "HERPUD1", "DEFB1", "SPP1", "AKR1C3", "ACAT2", "PEG3", "APOA2", "SDF2L1", "APOE", "NDUFC2", "ITM2B" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "RNASEH2C", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 132, "observed_counteralignment": 0.0216855909190419, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.0116222565993666 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "exploratory_multisource_core", "source_direction_agreement": 1, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 9.52581, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": 0.18037, "fusion_pos_fdr": 0.685016, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; 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Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "RNF8", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 122, "observed_counteralignment": 0.0393946134940323, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.0463522337377071 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 4.10534, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; 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Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "WDR4", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 108, "observed_counteralignment": 0.0185197163615708, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": -0.1113008335232734 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "exploratory_multisource_core", "source_direction_agreement": 1, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 4.15911, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": -0.010262, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; 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Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "ZFP69B", "current_action": "verify_expression", "current_display_label": "Verify expression", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 81, "observed_counteralignment": 0.0563412545485794, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.1597582101821899 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.6666666666666666, "assessed_sources": 3 }, "muscle_context": { "skeletal_muscle_median_tpm": 0.155208, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 1.56814752, "correction_effects": { "dup2": { "logfc": -0.25690467, "fdr": 0.56079923 }, "dup2_9": { "logfc": 0.057161, "fdr": 0.94372095 }, "dup8_9": { "logfc": -0.17294162, "fdr": 0.7032864 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.08856089, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 1.77443151, "pseudotime_spearman_rho": -0.17103911, "pseudotime_spearman_fdr_among_21_candidates": 0.0225651, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.19857306, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 1.17982805, "median_fpkm": 0, "mean_log1p_fpkm": 0.25251622 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 0.10330081, "median_fpkm": 0, "mean_log1p_fpkm": 0.04926967 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 1.4533208, "median_fpkm": 0, "mean_log1p_fpkm": 0.16121097 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 4.27833245, "median_fpkm": 0, "mean_log1p_fpkm": 0.3479682 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.44459837 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.33747792 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.13886301 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.1063427 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.32434795 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.031844 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.15990657 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.04953502 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.10949298 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.17466618 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "PLA2G2A", "SERPINA3", "RARRES2", "CDT1", "PYCARD", "MKI67", "MT2A", "SPP1", "SERPINE1", "ACTA1", "CTNNAL1", "C3" ], "disease_like": [ "DLK1", "APOA1", "TSPAN8", "COMP", "MLXIPL", "GPX3", "CSRP2", "CDH2", "CTHRC1", "HMGB2", "KRT18", "TNFRSF12A" ], "observed_aligned": [ "AFP", "TF", "GDF15", "MGST1", "DCBLD2", "APOC3", "MPC1", "FABP1", "HIST1H1E", "DHRS2", "LCN15", "APOH" ], "observed_opposed": [ "TYMS", "S100P", "CKS1B", "STMN1", "CENPF", "IGFBP1", "HMGB2", "H2AFZ", "GMNN", "MCM3", "DEK", "FEN1" ], "largest_model_errors": [ "AFP", "TYMS", "CKS1B", "S100P", "FN1", "STMN1", "LYZ", "TESC", "SMARCA1", "TM7SF3", "CENPF", "HMGB2" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "ZNF133", "current_action": "muscle_assay", "current_display_label": "Muscle-context assay", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 84, "observed_counteralignment": 0.0638177433316608, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.1183975711464881 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.75, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 4.55781, "moderate_dependency_flag": false, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": true, "fusion_screen_assessed": true, "fusion_pos_lfc": -0.003533, "fusion_pos_fdr": 0.999999, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 2.04897248, "correction_effects": { "dup2": { "logfc": 0.13505433, "fdr": 0.69395003 }, "dup2_9": { "logfc": -0.03955329, "fdr": 0.96061378 }, "dup8_9": { "logfc": -0.0848011, "fdr": 0.83341441 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.25830258, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": -0.03481638, "pseudotime_spearman_rho": -0.02935485, "pseudotime_spearman_fdr_among_21_candidates": 0.80232802, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.27414853, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 2.20353806, "median_fpkm": 0, "mean_log1p_fpkm": 0.41552225 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 2.88750254, "median_fpkm": 0, "mean_log1p_fpkm": 0.28320335 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 5.042558, "median_fpkm": 0, "mean_log1p_fpkm": 0.39655446 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 2.14861249, "median_fpkm": 0, "mean_log1p_fpkm": 0.4903935 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.31640286 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.56224916 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.41166732 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 0.33362046 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.30539995 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.18744497 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.48723975 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.64637092 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.37204345 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.25640418 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "APOA1", "CTHRC1", "MKI67", "STMN1", "CDT1", "CTNNAL1", "SERPINE1", "SOD2", "MT2A", "SPP1", "MLXIPL", "GPX3" ], "disease_like": [ "SERPINA3", "DLK1", "PLA2G2A", "APOE", "SERPINA1", "C3", "HMGB2", "COMP", "TSPAN8", "CSRP2", "SORL1", "C2" ], "observed_aligned": [ "TAGLN", "ALB", "HELLS", "A2M", "FDFT1", "TUBB", "RBP4", "IGFBP1", "TUBB4B", "ANGPTL8", "TUBA1C", "APOH" ], "observed_opposed": [ "H2AFZ", "PTTG1", "CENPW", "CCDC85B", "BIRC5", "CDC20", "ANP32E", "FGB", "CENPF", "CKS1B", "HMGB2", "FN1" ], "largest_model_errors": [ "H2AFZ", "STMN1", "TUBA1B", "HMGB2", "PTTG1", "JUND", "CENPW", "CENPF", "FDFT1", "CCDC85B", "BIRC5", "CDC20" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." }, { "gene": "ZNF236", "current_action": "risk_review", "current_display_label": "Risk/context review", "current_numeric_rank": null, "observed_crispri": { "available": true, "context": "HepG2", "modality": "CRISPRi / knockdown-like", "observed_cells": 202, "observed_counteralignment": 0.0596269867166334, "target_specific_predictive_support": "not_supported_by_strict_direct_gate", "model_vs_observed_cosine": 0.518381655216217 }, "disease_context": { "integrated_prior_direction": "up", "source_direction_state": "direction_conflicted", "source_direction_agreement": 0.5, "assessed_sources": 4 }, "muscle_context": { "skeletal_muscle_median_tpm": 2.00686, "moderate_dependency_flag": true, "independent_muscle_or_dmd_perturbation_replication": false }, "external_evidence": { "human_myoblast_fusion": { "accession": "GSE293514", "in_myo_crispr_library": false, "fusion_screen_assessed": false, "fusion_pos_lfc": 0, "fusion_pos_fdr": 0, "fusion_hit_fdr_lt_0_1": false, "individually_validated_hit": false, "external_context_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY", "interpretation": "human-myoblast fusion context only; not direct DMD candidate perturbation validation" }, "dmd_crispr_correction_reference": { "accession": "GSE272233", "observed_in_filtered_matrix": true, "mean_log_cpm": 4.91232045, "correction_effects": { "dup2": { "logfc": 0.07980343, "fdr": 0.63453741 }, "dup2_9": { "logfc": 0.11648346, "fdr": 0.60944169 }, "dup8_9": { "logfc": 0.03624907, "fdr": 0.85618164 } }, "significant_correction_contrasts_fdr_0_05": 0, "exploratory_reversal_contrasts_fdr_0_05": 0, "correction_direction_state": "no_repair_contrast_fdr_lt_0_05", "interpretation": "candidate transcript response to DMD correction; not a perturbation effect of this candidate" }, "myogenic_trajectory_reference": { "accession": "GSE52529", "measured": true, "detected_fraction_gt_0": 0.46863469, "physical_time_log2_ratio_72h_vs_0h_pseudocount_0_1": 1.25030112, "pseudotime_spearman_rho": -0.16206425, "pseudotime_spearman_fdr_among_21_candidates": 0.02854336, "physical_time_kruskal_wallis_fdr_among_21_candidates": 0.30584481, "trajectory_state": "no_strong_monotonic_pseudotime_association", "time_profile": [ { "hours": 0, "cell_count": 69, "mean_fpkm": 1.41373969, "median_fpkm": 0.0502515, "mean_log1p_fpkm": 0.50008631 }, { "hours": 24, "cell_count": 74, "mean_fpkm": 3.87116902, "median_fpkm": 0, "mean_log1p_fpkm": 0.5276825 }, { "hours": 48, "cell_count": 79, "mean_fpkm": 4.68460055, "median_fpkm": 0, "mean_log1p_fpkm": 0.68951035 }, { "hours": 72, "cell_count": 49, "mean_fpkm": 3.50105156, "median_fpkm": 0.304452, "mean_log1p_fpkm": 0.76318423 } ], "pseudotime_profile": [ { "bin": 1, "cell_count": 27, "median_pseudotime": 9.02226494, "mean_log1p_fpkm": 0.32257669 }, { "bin": 2, "cell_count": 27, "median_pseudotime": 19.3990258, "mean_log1p_fpkm": 0.64997691 }, { "bin": 3, "cell_count": 27, "median_pseudotime": 31.88462671, "mean_log1p_fpkm": 0.46281663 }, { "bin": 4, "cell_count": 27, "median_pseudotime": 41.82137577, "mean_log1p_fpkm": 1.23826713 }, { "bin": 5, "cell_count": 27, "median_pseudotime": 44.08333053, "mean_log1p_fpkm": 0.85690526 }, { "bin": 6, "cell_count": 27, "median_pseudotime": 46.16188448, "mean_log1p_fpkm": 0.57994334 }, { "bin": 7, "cell_count": 27, "median_pseudotime": 50.61779133, "mean_log1p_fpkm": 0.44015146 }, { "bin": 8, "cell_count": 27, "median_pseudotime": 57.09142445, "mean_log1p_fpkm": 0.60064821 }, { "bin": 9, "cell_count": 27, "median_pseudotime": 63.9866916, "mean_log1p_fpkm": 0.5330134 }, { "bin": 10, "cell_count": 28, "median_pseudotime": 73.10195975, "mean_log1p_fpkm": 0.42663328 } ], "perturbation_conditioned": false, "interpretation": "Descriptive expression trajectory in unperturbed differentiating human primary skeletal myoblasts; not a perturbation response." }, "crispra_combination_calibration": { "accession": "GSE133344", "cell_line": "K562", "present_as_expression_feature": true, "confirmed_as_crispra_target": null, "direct_candidate_overexpression_evidence": false, "interpretation": "Feature-list coverage only; target status is not inferable from the filtered-gene file." } }, "response_program_inputs": { "counteraligned": [ "PLA2G2A", "SERPINA3", "MKI67", "SPP1", "CTHRC1", "MLXIPL", "STMN1", "CDT1", "RARRES2", "EPB41L1", "SYNE1", "CKB" ], "disease_like": [ "DLK1", "TSPAN8", "APOE", "HMGB2", "MATN3", "CSRP2", "SOD2", "TNFRSF12A", "SCN9A", "GPX3", "PLTP", "COMP" ], "observed_aligned": [ "STMN1", "HMGB2", "TUBA1B", "CENPF", "H2AFZ", "PCLAF", "TUBB", "HMGB1", "MKI67", "ANGPTL8", "TOP2A", "DEK" ], "observed_opposed": [ "AFP", "APOH", "PEG10", "GAS5", "GLUD1", "APOB", "MALAT1", "CYB5A", "DLK1", "APOM", "SCD", "ATF4" ], "largest_model_errors": [ "ALB", "SAA4", "LGALS3", "AFP", "NKD1", "AKR1C1", "STMN1", "ANGPTL8", "HPD", "GLRX", "SERPINA1", "H2AFZ" ] }, "program_input_boundary": "Compact top-gene lists from the frozen candidate record are used for descriptive panel overlap. Full-vector enrichment and pathway-activity inference are not performed in the browser." } ], "claim_boundary": "This browser exposes observed evidence, descriptive program overlap, bounded external reference layers, a real unperturbed myogenic time course and an additive-pair hypothesis. External candidate transcript trajectories and correction-associated changes are not candidate perturbation effects. It does not estimate genetic interaction, formal pathway enrichment, knockout, overexpression, perturbation-conditioned fate, treatment effect or clinical utility." }