Additional file 6 of Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b
Creators: name: Hosseini-Gerami, Layla
name: Ficulle, Elena
name: Humphryes-Kirilov, Neil
name: Airey, David C.
name: Scherschel, James
name: Kananathan, Sarubini
name: Eastwood, Brian J.
name: Bose, Suchira
name: Collier, David A.
name: Laing, Emma
name: Evans, David
name: Broughton, Howard
name: Bender, Andreas
Publisher: name: figshare
Year: 2023
Subjects: subject: Biochemistry
subject: Molecular Biology
subject: Neuroscience
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: 110309 Infectious Diseases

description: Additional file 6. Figure S1. Heatmap showing the differential expression (as log2-fold change) of significantly differentially expressed genes when comparing hAD tau seeded RCNs to unseeded RCNs (Seed - Control) and Anle138-treated hAD tau seeded RCNs to vehicle control hAD tau seeded RCNs (Anle + Seed - Seed) at DIV (days in vitro) 3. Figure S2. Heatmap showing the differential expression (as log2-fold change) of significantly differentially expressed genes when comparing hAD tau seeded RCNs to unseeded RCNs (Seed - Control) and Anle138-treated hAD tau seeded RCNs to vehicle control hAD tau seeded RCNs (Anle + Seed - Seed) at DIV (days in vitro) 7. Figure S3. Heatmap showing the differential expression (as log2-fold change) of significantly differentially expressed genes when comparing hAD tau seeded RCNs to unseeded RCNs (Seed - Control) and Anle138-treated hAD tau seeded RCNs to vehicle control hAD tau seeded RCNs (Anle + Seed - Seed) at DIV (days in vitro) 14. Figure S4. Most significantly enriched pathways at each time point in Anle138b-treated unseeded RCNs. Significance level of p = 0.05 is indicated as a red dashed line on the x-axis. Figure S5. Most enriched pathways at each time point in Anle138b-treated hAD Tau seeded RCNs. Significance level of p = 0.05 is indicated as a red dashed line on the x-axis. Table S1. DEGs overlapping with Open Targets (July 2020) Alzheimer’s Disease association list (bold) or Tauopathies association list (underlined) in each Anle138b perturbation experiment, as well as the overall overlap with AD + Tauopathies, and the corresponding Odd’s Ratio and p-value calculated with Fisher’s Exact Test. Table S2. Full list of overlapping pathways (FDR-adjusted p-value &lt;= 0.05) between different Anle138b perturbation (hAD seeded or unseeded) RCN experiment at each time point. Table S3. Node list for each signalling subnetwork reconstructed from causal reasoning analysis of Anle138b transcriptomic data on unseeded and hAD tau seeded RCNs, bolded has prior disease association (from Open Targets). Table S4. Target prediction results from PIDGINv4 using the Anle138b chemical structure, predictions with AD (applicability domain) cutoff of 50 and probability cutoff of 0.3. Column definitions: Activity = bioactivity in uM, Probability = random forest probability of activity at stated threshold, ad = applicability domain percentile of the model, Nearest Neighbour ChEMBL ID = closest compound in the model training set, Similarity = Tanimoto similarity of the nearest neighbour, Alz Gene/Tau Gene = OpenTargets gene associations.