MOTIVATION: Limited cohort of transcription factors is capable to structure various gene-expression patterns. Transcriptional cooperativity (TC) is deemed to be the main mechanism of complexity and precision in regulatory programs. Although many data types generated from numerous experimental technologies are utilized in an attempt to understand combinational transcriptional regulation, complementary computational approach that can integrate diverse data resources and assimilate them into biological model is still under development. RESULTS: We developed a novel Bayesian approach for integrative analysis of proteomic, transcriptomic and genomic data to identify specific TC. The model evaluation demonstrated distinguishable power of features derived from distinct data sources and their essentiality to model performance. Our model outperformed other classifiers and alternative methods. The application that contextualized TC within hepatocarcinogenesis revealed carcinoma associated alterations. Derived TC networks were highly significant in capturing validated cooperativity as well as revealing novel ones. Our methodology is the first multiple data integration approach to predict dynamic nature of TC. It is promising in identifying tissue- or disease-specific TC and can further facilitate the interpretation of underlying mechanisms for various physiological conditions. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.