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A New Bliss Independence Model to Analyze Drug Combination Data
Open accessAbstract
The Bliss independence model is widely used to analyze drug combination data when screening for candidate drug combinations. The method compares the observed combination response (Y(O)) with the predicted combination response (Y(P)), which was obtained based on the assumption that there is no effect from drug-drug interactions. Typically, the combination effect is declared synergistic if Y(O) is greater than Y(P). However, this method lacks statistical rigor because it does not take into account the variability of the response measures and can frequently cause false-positive claims. In this article, we introduce a two-stage response surface model to describe the drug interaction across all dose combinations tested. This new method enables robust statistical testing for synergism at any dose combination, thus reducing the risk of false positives. The use of the method is illustrated through an application describing statistically significant "synergy regions" for candidate drug combinations targeting epidermal growth factor receptor and the insulin-like growth factor 1 receptor.
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“Even when replicates are available, multiple testing problems arise from repeatedly performing a statistical test across all combination doses (Zhao et al 2014).”
From Evaluation of Drug Combination Effect Using a Bliss Independence Dose–Response Surface Model (2018) · cites this paper as Zhao et al 2014
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“Combination treatment was analyzed for synergism using a Bliss independence-based twostage response surface model as described (Zhao et al., 2014).”
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SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models
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“Potential drug synergy was determined by BLISS analysis as: Yab,P = Ya + Yb − YaYb, where Ya stands for the percentage inhibition of drug a and Yb stands for the percentage inhibition of drug b (48).”
MethodSHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
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“Bliss analysis Potential drug synergy was assessed by Bliss analysis as Yab,P = Ya + Yb − YaYb, where Ya stands for percentage inhibition of drug a and Yb stands for percentage inhibition of drug b (Zhao et al., 2014).”
MethodWhat is synergy? The Saariselkä agreement revisited
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Cellular adaptation to cancer therapy along a resistance continuum
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“The effect of this drug combination was calculated using the Bliss synergy score 41 .”
Evaluation of Drug Combination Effect Using a Bliss Independence Dose–Response Surface Model
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“The expected value is computed using the Bliss independence model(17) as reference, which assumes that two drugs exhibit their effect independently.(18)”
MethodMethods for High-throughput Drug Combination Screening and Synergy Scoring
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Statistical determination of synergy based on Bliss definition of drugs independence
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“A typical example of an ad hoc dose-response model [37] is a quadratic polynomial and as such can be negative and/or not an increasing function of dose concentration.”
Rios‐Doria, J., Durham, N. M., Wetzel, L. K., Rothstein, R. P., Chesebrough, J. W., Holoweckyj, N., Zhao, W., Leow, C. C., & Hollingsworth, R. E. (2015) · Neoplasia · doi:10.1016/j.neo.2015.08.004 · Cited by 177
“Statistical Analysis for Synergy Statistical analysis for synergy was performed using a Bliss independence model [23].”
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Rios‐Doria, J., Harper, J. W., Rothstein, R. P., Wetzel, L. K., Chesebrough, J. W., Marrero, A. M., Chen, C., Strout, P., Mulgrew, K. A., McGlinchey, K., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2854 · Cited by 150
“Statistical Analysis Statistical analysis for synergy was determined using a Bliss Independence model, and described in detail elsewhere (8, 31).”
MethodSelf-citationABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth
Remsberg, J. R., Suciu, R. M., Zambetti, N. A., Hanigan, T. W., Firestone, A. J., Sheth, A. I., Long, A. M., Ngo, N., Lum, K. M., Henry, C. L., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00785-8 · Cited by 144
Predictive approaches for drug combination discovery in cancer
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A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells*
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“We used a Bliss independence model (54) to predict the additive response to the combination for each of these sites, based on the response of that site to each single drug.”
MethodMeyer, L. K., Verbist, K., Albeituni, S., Scull, B., Bassett, R., Stroh, A. N., Sheppard, H., Allen, C. E., Hermiston, M. L., & Nichols, K. E. (2020) · Blood · doi:10.1182/blood.2020006075 · Cited by 104
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“Loewe Additivity model becomes unusable when a dose–effect curve is not available or difficult to model [33].”
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“The predicted combined affected fraction with values lower than the experimental one is considered synergistic.(36)”
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Raiesi, F., & Sadeghi, E. (2018) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2018.10.079 · Cited by 86
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RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3
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“Drug Synergy Analysis Drug synergy was measured by Bliss independence analysis (Zhao et al., 2014) as described (Dhawan et al.”
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“The black dashed line represents the theoretical activation curve obtained for the additive combination of EE2, TNC, and TBT activities calculated using the Bliss independence model (20).”
MethodInfluentialAdditivity of inhibitory effects in multidrug combinations
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Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application
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Pharmacological mechanisms leading to synergy in fixed-dose dual bronchodilator therapy
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Combination Therapy to Treat Fungal Biofilm-Based Infections
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“The Bliss independence model [52, 53] was used to define the pairwise drug combination effects in concentration combination matrices.”
MethodJensen, K. V., Cseh, O., Aman, A. M., Weiss, S., & Luchman, H. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189670 · Cited by 68
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Eade, C. R., Hung, C., Bullard, B., Gonzalez-Escobedo, G., Gunn, J. S., & Altier, C. (2016) · Infection and Immunity · doi:10.1128/iai.00177-16 · Cited by 69
“Using assessments for Bliss independence, we determined that the bile acids function synergistically, with the activity of the combined acids being greater than the additive activity of the individual acids (see Text S1 in the supplemental material) (44, 45).”
MethodPolymeric Nanoparticle Delivery of Combination Therapy with Synergistic Effects in Ovarian Cancer
Levit, S. L., & Tang, C. (2021) · Nanomaterials · doi:10.3390/nano11041048 · Cited by 57
“The second assumption accounts for similar mechanisms of action of the two compounds [35,36].”
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Mo, H., Liu, X., Xue, Y., Chen, H., Guo, S., Li, Z., Wang, S., Li, C., Han, J., Fu, M., et al. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01642-5 · Cited by 55
“Bliss synergy scores were calculated and plotted using the SynergyFinder package in R [24, 25].”
MethodKohlmeyer, J. L., Kaemmer, C. A., Pulliam, C. F., Maharjan, C. K., Samayoa, A. M., Major, H. J., Cornick, K. E., Knepper-Adrian, V., Khanna, R., Sieren, J. C., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2706 · Cited by 52
“The Bliss independence method (65) was used to evaluate synergism between varying concentrations of palbociclib and dinaciclib in sNF96.”
MethodNunes, C., Depestel, L., Mus, L. M., Keller, K. M., Delhaye, L., Louwagie, A., Rishfi, M., Whale, A. J., Kara, N., Andrews, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn1382 · Cited by 51
“The synergism was computed according to the Bliss independent (BI) method (75) using the HTSplotter tool (75).”
MethodLin, P., Ren, Y., Yan, X., Luo, Y., Zhang, H., Kesarwani, M., Bu, J., Zhan, D., Zhou, Y., Tang, Y., et al. (2018) · Haematologica · doi:10.3324/haematol.2018.197749 · Cited by 47
“The combined inhibitory effect was predicted using the Bliss independent model.(28,29) Our data indicate that BCI and Ara-C have statistically significant synergistic effects on NRF2 activated SKM-1 cells (%survival, predicted 70.”
MethodAmbrosini, G., Do, C., Tycko, B., Realubit, R. B., Karan, C., Musi, E., Carvajal, R. D., Chua, V. Y. L., Aplin, A. E., & Schwartz, G. K. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3177 · Cited by 48
“6 individual drug treatment and the corresponding drug combination response, an excess over Bliss for each combination was derived (21).”
Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal
Stoszko, M., Crignis, E. D., Rokx, C., Khalid, M. M., Lungu, C., Palstra, R.-J. T. S., Kan, T. W., Boucher, C. A., Verbon, A., Dykhuizen, E. C., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.11.047 · Cited by 45
“; A11 (5-(4-chlorophenyl)-6-ethyl2,4-pyrimidinediamine (BRD-K88429204-001-18-7), Sigma Aldrich); C09 (2-phenylethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate (BRDK91370081-001-04-6), MP Biomedicals, Eindhoven, The Netherlands).”
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“In the experiments in which neonicotinoids were used in combination, we used ‘effect-based strategy’ method, in particular, the Bliss independence model (see Zhao et al., 2014; Foucquier and Guedj, 2015).”
BackgroundMethodAlbert, B. J., Niu, A., Ramani, R., Marshall, G. R., Wender, P. A., Williams, R. M., Ratner, L., Barnes, A. B., & Kyei, G. B. (2017) · Scientific Reports · doi:10.1038/s41598-017-07814-4 · Cited by 42
“S2) 57 .”
Vu, K., Wu, C.-H., Yang, C., Zhan, A., Cavallone, E., Berry, W., Heeter, P., Pincus, L. B., Wieduwilt, M. J., William, B. M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2152 · Cited by 40
“Preclinical studies For combination assays, the interaction between romidepsin and doxorubicin was evaluated using the Bliss Independence model (25).”
MethodCai, J., Sun, X., Guo, H., Qu, X., Huang, H., Yu, C. J., Wu, H., Gao, Y., Kong, X., & Xia, Q. (2020) · Oncogenesis · doi:10.1038/s41389-020-00287-7 · Cited by 37
Amzallag, A., Ramaswamy, S., & Benes, C. H. (2019) · BMC Bioinformatics · doi:10.1186/s12859-019-2642-7 · Cited by 37
Wickstroem, K., Karlsson, J., Ellingsen, C., Cruciani, V., Kristian, A., Hagemann, U. B., Bjerke, R. M., Ryan, O. B., Lindén, L., Mumberg, D., et al. (2019) · Pharmaceuticals · doi:10.3390/ph12040155 · Cited by 38
“Based on calculations using the Bliss additivity model, we determined that the combination effect was synergistic when using 125 kBq/kg bw HER2-TTC + 50 mg/kg bw olaparib and 300 kBq/kg bw HER2-TTC + 50 mg/kg bw olaparib [26] (Table S3).”
Methodde Oliveira, H. C., Joffe, L. S., Simon, K. S., Castelli, R. F., Reis, F. C. G., Bryan, A. M., Borges, B. S., Medeiros, L. C. S., Bocca, A. L., Poeta, M. D., et al. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00286-20 · Cited by 37
“Considering the differences in chemical nature and cellular targets of fenbendazole and amphotericin B, we also calculated the Bliss synergism scores (51) against C.”
BackgroundPatient-Derived Cells to Guide Targeted Therapy for Advanced Lung Adenocarcinoma
Kim, S., Lee, J. Y., Kim, D., Joo, H. S., Yun, M. R., Jung, D., Yun, J., Heo, S. G., Ahn, B., Park, C. W., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56356-4 · Cited by 40
Anti‐Tumorigenic Potential of a Novel Orlistat‐AICAR Combination in Prostate Cancer Cells
Wright, C. A., Iyer, A. K. V., Kaushik, V., & Azad, N. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26033 · Cited by 35
“The Bliss model was used to compute the expected combined effects of two drugs as the product of their individual effects based on the assumption that there is no effect from drug-drug interactions, as previously described [Bliss, 1939; Zhao et al., 2014].”
MethodDrug Combination Modeling: Methods and Applications in Drug Development
Pearson, R. A., Wicha, S. G., & Okour, M. (2022) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.2128 · Cited by 39
Huber, A. D., Wright, W. C., Lin, W., Majumder, K., Low, J. A., Wu, J., Buchman, C. D., Pintel, D. J., & Chen, T. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03505-y · Cited by 34
“1 3 combination of EE2 and TNC calculated using the Bliss independence model [51].”
MethodHe, M., Wang, D., Zou, D., Wang, C., Lopes-Bastos, B., Jiang, W. G., Chester, J. D., Zhou, Q., & Cai, J. (2016) · Oncotarget · doi:10.18632/oncotarget.13413 · Cited by 34
“In order to assess the combined effects of cisplatin and curcumin on the ovarian cancer spheroids, the responses were measured by Bliss independence reference models of synergy [43], using Graphpad Prism® (Version 6.”
MethodCurrier, M. A., Sprague, L., Rizvi, T. A., Nartker, B. A., Chen, C., Wang, P.-Y., Hutzen, B. J., Franczek, M., Patel, A. V., Chaney, K. E., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14885 · Cited by 32
“We thank Dr. Winfried Just (Ohio University, Athens, OH) for helpful consultation regarding Bliss Independence Modeling of in vivo synergy.”
MethodSomers, K., Evans, K., Cheung, L., Karsa, M., Pritchard, T., Kosciolek, A., Bongers, A., El‐Ayoubi, A., Forgham, H., Middlemiss, S., et al. (2019) · Leukemia · doi:10.1038/s41375-019-0683-6 · Cited by 32
Shigeta, S., Lui, G. Y. L., Shaw, R. C., Moser, R. D., Gurley, K. E., Durenberger, G., Rosati, R., Diaz, R. L., Ince, T. A., Swisher, E. M., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0809 · Cited by 29
“Drug synergy was calculated using the Bliss method and graphed using Combenefit software (23, 24).”
MethodCombinatorial drug approaches to tackleCandida albicansbiofilms
Cremer, K. D., Staes, I., Delattin, N., Cammue, B. P. A., Thevissen, K., & Brucker, K. D. (2015) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2015.1056162 · Cited by 31
Wilkinson, M., Smith, H. G., McEntee, G., Kyula, J., Pencavel, T. D., Mansfield, D., Khan, A., Roulstone, V., Hayes, A. J., & Harrington, K. J. (2016) · Oncotarget · doi:10.18632/oncotarget.12820 · Cited by 30
“A recently published modification of Bliss independence analysis could not be used because of the number of variables within our dataset [58].”
MethodGrundy, M. A., Balakrishnan, S., Fox, M., Seedhouse, C., & Russell, N. H. (2018) · Oncotarget · doi:10.18632/oncotarget.26540 · Cited by 30
The recent progress of deep-learning-based in silico prediction of drug combination
Liu, H., Fan, Z., Lin, J., Yang, Y., Ran, T., & Chen, H. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103625 · Cited by 29
Meyer, L. K., Delgado-Martín, C., Maude, S. L., Shannon, K., Teachey, D. T., & Hermiston, M. L. (2019) · PLoS ONE · doi:10.1371/journal.pone.0220026 · Cited by 29
“Drug-drug interactions were assessed using the Bliss independence model of synergy [14]”
MethodSalimi, A., Schroeder, K. M., Schemionek, M., Vieri, M., Maletzke, S., Gezer, D., Masouleh, B. K., & Appelmann, I. (2022) · BMC Cancer · doi:10.1186/s12885-022-09775-y · Cited by 29
“The Bliss formula was used to analyze the efficacy of drug combination in comparison with monotherapy, using equation: Yab,P = (Ya + Yb)- (Ya × Yb), which defines the concepts of synergy, antagonism and additive effects between two inhibitory drugs [25].”
MethodAhn, S., Saha, A., Clark, R., Kolonin, M. G., & DiGiovanni, J. (2022) · Oncogene · doi:10.1038/s41388-022-02466-9 · Cited by 29
“To investigate the synergistic, anticancer effect of the combination of AMD3100 and D-CAN, we used the Bliss Independence Model as previously described [71].”
MethodActivity of the antiestrogenic cajanin stilbene acid towards breast cancer
Fu, Y., Kadioglu, O., Wiench, B., Wei, Z., Wang, W., Luo, M., Yang, X., Gu, C., Zu, Y., & Efferth, T. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.06.004 · Cited by 29
“3-μM and 1-μM tamoxifen resulted in a synergistic effect towards inhibition ofMCF-7 cell growth as evaluated by Bliss model equation [34].”
MethodInformatics Approaches for Predicting, Understanding, and Testing Cancer Drug Combinations
Tang, J. P. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7154-1_30 · Cited by 29
“Bliss The effect as if two drugs are acting independently Synergy landscape [78]”
BackgroundSingle-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity
da Costa, A. A. B. A., Somuncu, O., Ravindranathan, R., Mukkavalli, S., Martignetti, D. B., Nguyen, H. Q., Jiao, Y., Lamarre, B. P., Sadatrezaei, G., Moreau, L. A., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-4007 · Cited by 29
“Assessment of synergy was calculated based on the Bliss model of synergy using Combenefit software (40, 42).”
A novel resveratrol–salinomycin combination sensitizes ER-positive breast cancer cells to apoptosis
Venkatadri, R., Iyer, A. K. V., Kaushik, V., & Azad, N. (2017) · Pharmacological Reports · doi:10.1016/j.pharep.2017.03.024 · Cited by 27
Somers, K., Wen, V. W., Middlemiss, S., Osborne, B., Forgham, H., Jung, M., Karsa, M., Clifton, M., Bongers, A., Gao, J., et al. (2019) · Oncogene · doi:10.1038/s41388-018-0666-5 · Cited by 28
Bollmann, L. M., Skerhut, A. J., Asfaha, Y., Horstick‐Muche, N., Hanenberg, H., Hamacher, A., Kurz, T., & Kassack, M. U. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113398 · Cited by 25
Ono, A., Sano, O., Kazetani, K., Muraki, T., Imamura, K., Sumi, H., Matsui, J., & Iwata, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181243 · Cited by 25
Weidenauer, K., Schmidt, C., Rohde, C., Pauli, C., Blank, M. F., Heid, D., Waclawiczek, A., Corbacioglu, A., Göllner, S., Lotze, M., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01951-8 · Cited by 26
“To identify synergistic effects of drug combinations, a synergy score was computed using the Bliss Independence Model [22].”
BackgroundMethodRuiz, N. Q., Campo, Y. C., Stashenko, E. E., & Fuentes, J. L. (2017) · Photochemistry and Photobiology · doi:10.1111/php.12735 · Cited by 25
“This model used the probability theory of complete additive effect (39), where the observed (Yo) and expected (YE) responses of mixtures were compared.”
BackgroundMethodInhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer
Jung, M., Park, K. H., Kim, H. M., Kim, T. S., Zhang, X., Park, S.-M., Beom, S., Kim, H. S., Cheong, J., Chung, H. C., et al. (2019) · Gastric Cancer · doi:10.1007/s10120-019-00971-7 · Cited by 25
Coates, J. T. T., Rodríguez‐Berriguete, G., Puliyadi, R., Ashton, T. M., Prevo, R., Wing, A., Granata, G., Pirovano, G., McKenna, G. W., & Higgins, G. S. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-00343-6 · Cited by 25
Deusenbery, C. B., Carneiro, O., Oberkfell, C., & Shukla, A. (2023) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.3c00239 · Cited by 24
Venetoclax-based Rational Combinations are Effective in Models of MYCN -amplified Neuroblastoma
Dalton, K. M., Krytska, K., Lochmann, T. L., Sano, R., Casey, C. E., D'Aulerio, A., Khan, Q. A., Crowther, G. S., Coon, C. M., Cai, J., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0710 · Cited by 26
“The Bliss excess is demonstrated for each datum as the difference between the Bliss expectation and the observed growth inhibition induced by each combination (26, 27).”
BackgroundSynergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL
Seyfried, F., Stirnweiß, F. U., Niedermayer, A., Enzenmüller, S., Hörl, R. L., Münch, V., Köhrer, S., Debatin, K., & Meyer, L. H. (2022) · Leukemia · doi:10.1038/s41375-021-01502-z · Cited by 24
“5A) and determining synergy scores (Bliss independence model [23, 24]; Fig.”
Backgroundde Groot, E., Varghese, S., Tan, L., Knighton, B. G., Sobieski, M. M., Nguyen, N. H., Park, Y. S., Powell, R. T., Lorenzi, P. L., Zheng, B., et al. (2022) · Cancer & Metabolism · doi:10.1186/s40170-022-00281-0 · Cited by 23
“Rigor and reproducibility of the combinatorial drug screening assay was performed in accordance with the NCATS Assay Guidance Manual [19], and a bootstrapped bliss independence model was used to calculate drug synergy [20].”
MethodJensen, K. V., Hao, X., Aman, A. M., Luchman, H. A., & Weiss, S. (2020) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaa020 · Cited by 23
“The JAK2/STAT3 pathway is a potent pro-survival signaling pathway and activated STAT3 is expressed at high levels in more than 90% of GBMs 32,43 and patient-derived BTSCs. 44 This led us to investigate the effectiveness of a JAK2 inhibitor, pacritinib, in combination with afatinib.”
Sahler, J., Eade, C. R., Altier, C., & March, J. C. (2018) · Infection and Immunity · doi:10.1128/iai.00674-17 · Cited by 22
“Synergy calculations were performed in Microsoft Excel testing for Bliss independence (42, 43).”
MethodWu, C.-H., Yang, C., Wang, L., Gao, H.-X., Rakhshandehroo, T., Afghani, S., Pincus, L. B., Balassanian, R., Rubenstein, J. L., Gill, R. M., et al. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.05.110 · Cited by 22
Asfaha, Y., Bollmann, L. M., Skerhut, A. J., Fischer, F., Horstick‐Muche, N., Roth, D., Wecker, M., Mammen, C., Smits, S. H. J., Fluegen, G., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115907 · Cited by 22
Panov, V. G., & Вараксин, А. Н. (2016) · Toxicology Mechanisms and Methods · doi:10.3109/15376516.2016.1139023 · Cited by 22
“Determination of a combined toxicity type is usually based on one of two competing concepts: the additivity paradigm or the independence paradigm (Greco et al., 1995; Zhao et al., 2014).”
BackgroundSweeney, S., Collins, M., Pandey, R., Chiou, J., Lodi, A., & Tiziani, S. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23163 · Cited by 22
Epidermal growth factor receptor activation confers resistance to lenvatinib in thyroid cancer cells
Ohno, K., Shibata, T., & Ito, K. (2022) · Cancer Science · doi:10.1111/cas.15465 · Cited by 20
mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer
Kumari, A., Gesumaria, L., Liu, Y.-J., Hughitt, V. K., Zhang, X., Ceribelli, M., Wilson, K. M., Klumpp-Thomas, C. A., Chen, L., McKnight, C. G., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.156657 · Cited by 21
“The synergy of various drug combinations was assessed using the excess Highest Single Agent (HSA) method, the response heat map, and the Δ Bliss heat map (46, 47).”
MethodZhang, W., Qi, L., Liu, Z., He, S., Wang, C., Wu, Y., Han, L., Liu, Z., Fu, Z., Tu, C., et al. (2023) · MedComm · doi:10.1002/mco2.317 · Cited by 20
Pei, F., Li, H., Henderson, M. J., Titus, S. A., Jadhav, A., Simeonov, A. M., Çobanoğlu, M. C., Mousavi, S. H., Shun, T., McDermott, L. A., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17378-y · Cited by 21
Wang, X., Zhang, G., Bian, Z., Chow, V., Grimaldi, M., Carivenc, C., Sirounian, S., Li, H., Sládeková, L., Motta, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56624-0 · Cited by 21
Chen, X., Zhuo, S., Xu, W., Chen, X., Huang, D., Sun, X., & Cheng, Y. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0852-4 · Cited by 20
“The interaction between radiation and IDH2 knockdown was analysed using the Bliss independence model.(19) Based on the inhibition rate (IR), the combined percentage inhibition, IRR+sh-IDH2, was predicted using IRR+sh-IDH2= IRR+ IRsh-IDH2− IRR × IRsh-IDH2 where IRR and IRsh-IDH2 were the IR of mono-treatment with radia…”
MethodKessler, B. E., Mishall, K. M., Kellett, M. D., Clark, E. G., Pugazhenthi, U., Pozdeyev, N. V., Kim, J., Tan, A. C., & Schweppe, R. E. (2018) · Oncogene · doi:10.1038/s41388-018-0617-1 · Cited by 20
Karsa, M., Kosciolek, A., Bongers, A., Mariana, A., Failes, T. W., Gifford, A. J., Kees, U. R., Cheung, L. C., Kotecha, R. S., Arndt, G. M., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01332-x · Cited by 20
“The occurrence of synergy was determined with the Bliss Independence model.(18,19) Bliss Prediction curves indicate the predicted % viability of the cells when exposed to the combination of compounds if both compounds work additively together.”
Method
Metadata
- Authors
- Zhao, W., Sachsenmeier, K., Zhang, L., Sult, E., Hollingsworth, R. E., & Yang, H.
- Affiliations
- AbbVie (United States) (US)
- Corresponding author
- Zhao, Wei
- Venue
- SLAS Discovery
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 19
- Issue
- 5
- Pages
- 817-821
- ISSN
- 2472-5552 (ISSN-L)
- OpenAlex
- W1980181290
- Cited by
- 322
- References
- 14
- Citations by year
- 2026: 46 · 2025: 33 · 2024: 29 · 2023: 45 · 2022: 40 · 2021: 19 · 2020: 26 · 2019: 23 · 2018: 17 · 2017: 17 · 2016: 14 · 2015: 11 · 2014: 2
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Management Science and Operations Research › Optimal Experimental Design Methods
- Keywords
- Bliss independence model, drug synergy, drug-drug interactions, false positive reduction, epidermal growth factor receptor, IGF-1 receptor, drug combination screening
- MeSH terms
- Algorithms, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Dose-Response Relationship, Drug, Drug Combinations, Drug Interactions, Drug Synergism, Humans, Lung Neoplasms, Models, Chemical, Neoplasms, Regression Analysis, Technology, Pharmaceutical, Signal Transduction, Receptor, IGF Type 1, Drug Resistance, Neoplasm, ErbB Receptors
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