Journal: iScience
Article Title: Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases
doi: 10.1016/j.isci.2026.115339
Figure Lengend Snippet: In vitro experimental validation of the complement-type doublets and triplets that were predicted via SYNERGIE for CRC (A) The top 18 predicted complement-type drug combinations for CRC using the SYNERGIE-ET. The horizontal axis represents the drug combinations, whereas the vertical axis corresponds to the five types of prediction scores (see ). Blue and green indicate the prediction scores for drug A and drug B, respectively, with the color intensity reflecting the magnitude of the scores. Details can be found in . (B–I) Comparison of the survival ratios of CRC cells among Asp, an antineoplastic drug, and their combination. Gray represents single drugs (singlets), and blue represents the combination (doublet). Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (J–O) Comparison of the survival ratios of CRC cells among PB, an antineoplastic drug, and their combination. These panels follow the same format as (B–I). (P) Heatmap of the dose-response synergy scores of Asp doublets. The vertical axis represents the doses of Asp, and the horizontal axis shows drugs predicted to be Asp partners. The color scale reflects the IA scores, with positive values indicating synergistic effects and negative values indicating nonsynergistic effects. Each box is annotated with the corresponding IA score. Data are presented as mean values from independent experiments. Standard deviation values are provided in the . (Q) Comparison of the dose-response survival ratios between Oxa, a first-line drug for CRC, alone (singlet) and the Oxa-Asp doublet. In the Oxa-Asp doublet, the dose of Asp was fixed at 1 mM while the dose of Oxa was varied. The horizontal and vertical axes represent the doses of Oxa (μM) and the mean survival ratios of CRC cells, respectively. Error bars represent standard deviations (SD). The gray and blue points correspond to Oxa and the Oxa-Asp combination, respectively. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. (R) Comparison of CRC cell survival ratios among singlets, doublets, and the triplet combination: Oxa, Asp, and Ibru. The horizontal axis represents the drugs, and the vertical axis represents the mean survival ratios. Error bars indicate SD. The color bar reflects the IA scores for each drug combination, with values indicating the IA scores. Disease abbreviations: CRC, colorectal cancer. Drug abbreviations: Asp, aspirin; Chl, chlorotrianisene; Ced, cediranib; Das, dasatinib; Ibru, ibrutinib; Inf, infigratinib; Luc, lucitanib; Mir, mirdametinib; Oxa, oxaliplatin; PB, sodium phenylbutyrate; Pim, pimasertib; Pon, ponatinib; Sar, saracatinib; Tac, tacedinaline; Tan, tanespimycin; and Van, vandetanib.
Article Snippet: The HT-29 human CRC cell line (HTB-38; ATCC) was obtained from the ATCC (Rockville, MD, USA).
Techniques: In Vitro, Biomarker Discovery, Comparison, Standard Deviation
