Top-10 NetPert genes (Twist1 network) Highest NetPert weights; all intermediates.Top-30 NetPert genes (Twist1 network) Weights decay smoothly past the top hubs.Top-50 NetPert genes (Twist1 network) Top-50 of 1,200 ranked subnetwork genes.Top-100 NetPert genes (Twist1 network) The full head of the ranking; long tail beyond.Top-20 betweenness-subset genes (subnetwork) Driver-to-response betweenness on the same subnetwork.Top-20 betweenness genes (full 17k network) Betweenness on the full IID+TRRUST network.Top-20 hubs by out-degree (full network) Raw connectivity leaders for hub-bias context.NetPert rank-weight curve Steep head (hub mediators), long tail of weak contributors.Betweenness rank-weight curve Same subnetwork, driver-to-response betweenness.NetPert weight by gene class Intermediates carry the weight; responses score low (excluded from own term).Top-k overlap between methods NetPert agrees more with betweenness than with raw degree at every cutoff.
Network
Response coverage 168/182 DE genes present; 14 genuinely absent (interactome incompleteness).Unconnected responses Mostly RIKEN / uncharacterised genes plus Gpr110, Fut2, Lphn3.Subnetwork composition 1 driver + intermediates + 168 in-network responses.Out-degree distribution Long-tailed connectivity, typical of interactomes.Weight histograms by class Response weights cluster near zero by construction.Full-network degree distribution 17k-gene interactome; long tail.Twist1 connectivity context Twist1 has 199 out-neighbours in the network.Driver-to-response distances 164 in-network responses reachable; all within a few steps.Shortest-path mediator frequency nodes most often on driver-to-response shortest paths.Edge provenance PPI dominates; TRRUST adds 5,551 unique directed regulatory edges.Response direction 97 up- vs 67 down-regulated in Twist1 organoids.
Assays
Dissemination readout Sema5a 0% (Gö-6976) to Col6a1 94.7%.IC50 distribution Nanomolar potencies from the dissemination screen.Potency vs effect IC50 against dissemination.Expression vs effect DE magnitude does not predict inhibition in this subset.NetPert vs assay Honest null: rho=+0.31, p=0.21 (responses, not intermediates).Betweenness vs assay Also null (rho=-0.10) — same underpowered response-only subset.NetPert vs expression Ranking is not a proxy for differential expression.NetPert vs |log2FC| Strong DE genes are not systematically top-ranked.Up vs down weights No systematic up/down bias in NetPert weights.Connectivity vs assay Hubness alone does not explain inhibition.Assay table All 18 genes with a dissemination readout.Assay panels (strongest) dissemination % with NetPert ranks, strongest 9 of 18.Assay panels (weakest) dissemination % with NetPert ranks, weakest 9 of 18.
Gene spotlights
Spotlight #1: Pdgfra Rank #1 NetPert intermediate with ranks, drugs and assay status.Spotlight #2: Htt Rank #2 NetPert intermediate with ranks, drugs and assay status.Spotlight #3: Tp53 Rank #3 NetPert intermediate with ranks, drugs and assay status.Spotlight #4: Ctnnb1 Rank #4 NetPert intermediate with ranks, drugs and assay status.Spotlight #5: Cdh1 Rank #5 NetPert intermediate with ranks, drugs and assay status.Spotlight #6: Zranb1 Rank #6 NetPert intermediate with ranks, drugs and assay status.Spotlight #7: Vim Rank #7 NetPert intermediate with ranks, drugs and assay status.Spotlight #8: Ppia Rank #8 NetPert intermediate with ranks, drugs and assay status.Spotlight #9: Stat3 Rank #9 NetPert intermediate with ranks, drugs and assay status.Spotlight #10: Clu Rank #10 NetPert intermediate with ranks, drugs and assay status.Spotlight #11: Stub1 Rank #11 NetPert intermediate with ranks, drugs and assay status.Spotlight #12: Nfkb1 Rank #12 NetPert intermediate with ranks, drugs and assay status.Spotlight #13: Ep300 Rank #13 NetPert intermediate with ranks, drugs and assay status.Spotlight #14: Sox2 Rank #14 NetPert intermediate with ranks, drugs and assay status.Spotlight #15: Col2a1 Rank #15 NetPert intermediate with ranks, drugs and assay status.Spotlight #16: Rela Rank #16 NetPert intermediate with ranks, drugs and assay status.Spotlight #17: Kif23 Rank #17 NetPert intermediate with ranks, drugs and assay status.Spotlight #18: Hif1a Rank #18 NetPert intermediate with ranks, drugs and assay status.Spotlight #19: Hdac6 Rank #19 NetPert intermediate with ranks, drugs and assay status.Spotlight #20: H4c1 Rank #20 NetPert intermediate with ranks, drugs and assay status.Spotlight #21: Pdgfrb Rank #21 NetPert intermediate with ranks, drugs and assay status.Spotlight #22: Stau1 Rank #22 NetPert intermediate with ranks, drugs and assay status.Spotlight #23: Hdac1 Rank #23 NetPert intermediate with ranks, drugs and assay status.Spotlight #24: Ikbkb Rank #24 NetPert intermediate with ranks, drugs and assay status.Spotlight #25: Tnf Rank #25 NetPert intermediate with ranks, drugs and assay status.Spotlight #26: Eif2b5 Rank #26 NetPert intermediate with ranks, drugs and assay status.Spotlight #27: Cul4a Rank #27 NetPert intermediate with ranks, drugs and assay status.Spotlight #28: Hdac2 Rank #28 NetPert intermediate with ranks, drugs and assay status.Spotlight #29: Esr1 Rank #29 NetPert intermediate with ranks, drugs and assay status.Spotlight #30: Ppp2ca Rank #30 NetPert intermediate with ranks, drugs and assay status.Spotlight #31: Mcm7 Rank #31 NetPert intermediate with ranks, drugs and assay status.Spotlight #32: Zyx Rank #32 NetPert intermediate with ranks, drugs and assay status.Spotlight #33: Tcf4 Rank #33 NetPert intermediate with ranks, drugs and assay status.Spotlight #34: Tcf3 Rank #34 NetPert intermediate with ranks, drugs and assay status.Spotlight #35: Fos Rank #35 NetPert intermediate with ranks, drugs and assay status.Spotlight #36: Ilf3 Rank #36 NetPert intermediate with ranks, drugs and assay status.Spotlight #37: Obsl1 Rank #37 NetPert intermediate with ranks, drugs and assay status.Spotlight #38: Epha3 Rank #38 NetPert intermediate with ranks, drugs and assay status.Spotlight #39: Trp53 Rank #39 NetPert intermediate with ranks, drugs and assay status.Spotlight #40: Hk2 Rank #40 NetPert intermediate with ranks, drugs and assay status.
Drugs
Compounds per gene Most genes map to 0; mapped ones carry up to 10 shown compounds.Top compounds Most promiscuous mappers within the 1,200-gene subnetwork.Druggable vs other Whether mapped targets score higher than unmapped genes.Top druggable intermediates Prioritised genes that already have compounds.Druggable enrichment Dashed line = background rate; above = enriched.Compounds: Pdgfra 10 mapped compounds for Pdgfra.Compounds: Stat3 10 mapped compounds for Stat3.Compounds: Rela 8 mapped compounds for Rela.Compounds: Hdac6 10 mapped compounds for Hdac6.Compounds: Ctnnb1 6 mapped compounds for Ctnnb1.Compounds: Nfkb1 6 mapped compounds for Nfkb1.Compounds: Hif1a 11 mapped compounds for Hif1a.
Method comparison
NetPert vs BC-sub Spearman rho=0.58 over 1200 genes.NetPert vs BC-full Spearman rho=0.59 over 1200 genes.NetPert vs out-degree Spearman rho=0.51 over 1200 genes.BC-sub vs BC-full Spearman rho=1.00 over 1200 genes.Rank shifts Where perturbation theory disagrees with shortest-path counting.NetPert winners Genes perturbation theory lifts above shortest-path ranking.NetPert losers Shortest-path hubs that diffusion down-weights.Intermediates only Method agreement on the genes NetPert is built to prioritise.Responses only Both methods score responses low; different floors.Agreement summary All pairwise rank/weight agreements in one place.Assay rho by method No method predicts the 18-gene response-only readout; honest null.
Overview
Summary table Every number from inputs.Pipeline schematic Six stages, no invented inputs.
Report-style
Score concentration NetPert top-10 hold 15% of total weight ().Method agreement panels Concentration and rank agreement between methods on .Edge-removal robustness Ranking stability when interactome edges are deleted.Relaxation sweep ranking is insensitive to the relaxation fraction.Hub-bias panels Connectivity and betweenness context for NetPert weights.Weight vs driver distance How influence decays with network distance from Twist1.Assay waterfall inhibition ordered with NetPert ranks annotated.Top-30 rank heatmap Where the four rankings agree and disagree.Path-type counts DIR = direct driver+response neighbours; DI/IR = one-sided; I = rest.Weights by path type Direct driver–response connectors score highest on .DIR enrichment Direct connectors enriched at the top of the ranking.Scorecard Headline numbers in one table.
Dashboards
Overview dashboard Ranking, distribution, concentration, agreement, robustness and sweep in one view.Robustness dashboard Edge-deletion stability plus relaxation sensitivity, with repeat intervals.Assay dashboard Every wet-lab readout crossed with every ranking.Network dashboard Degrees, provenance, composition, path types, hub bias and coverage together.Methods dashboard Scatters, heatmap, correlations and overlaps between all rankings.Drugs dashboard Coverage, top compounds, enrichment along ranks and top druggable genes.Paths dashboard DIR counts, weights, enrichment and the TRRUST ablation in one view.
