Terial offered at https://doi. org/10.1186/s12967-021-02791-9. Further file 1: Table S1. Topological attributes of disease-associated networks and identified functional modules as outlined by the minimum entropy criterion. Table S2. MCODE final results for CHB-associated networks, cirrhosis-associated networks, and HCC-associated networks. Table S3. The amount of overlapping pathways PRMT6 Molecular Weight amongst CHB, cirrhosis and HCC in 13 OAMs. Table S4. Relationships involving 24 Altered Pathways/overlapping pathways and CHB/cirrhosis/HCC supported by previous literature. Table S5. Extremely correlated gene pairs and best five vital genes in the 13 OAMs. Table S6. The associations among highly correlated genes in 13 OAMs and 3 diseases. Table S7. The relationships amongst 15 genes and HCC biomarkers in literature. Table S8. The classification evaluation indexes of candidate genes and gene combinations for HCC identification. Table S9. The 7 most precise rules and intergroup comparisons of cyp1a2, cyp2c19 and il6. Table S10. Topological parameters from the 15 genes located inside the OAMs. Table S11. The prime 3 compounds that impacted the 3 genes (cyp1a2, cyp2c19 and il6). Acknowledgements Not applicable. Authors’ contributions ZW and JW conceived, developed and coordinated the study. YC, WY, QL, JL, YZ, BL, DL, XL, HW, XX and YP performed the data analysis. SS and QC performed the experiments. YC, WY, ZW, JW and JN wrote and modified the manuscript. All authors study and approved the final manuscript. Funding This work was supported by the National Key Scientific and Technological Particular Project for “Significant New Drugs Development” (2017ZX09301059), the National Crucial Study and Improvement Plan of China (2018YFC1704701), the National Key Investigation and Improvement Plan of China (2017YFC1700406-2), the National Organic Science Foundation of China (81803966), along with the Basic Investigation Funds for the Central Public Welfare Investigation Institutes (ZZ13-YQ-029). Availability of information and supplies The datasets employed and/or analysed during the existing study are available from the corresponding author on affordable request.Conclusions Taken together, we showed that the three-gene set (cyp1a2-cyp2c19-il6) was optimized to distinguish HCC from non-tumor samples employing random forests with an AUC of 0.973. These findings indicated that the proposed sequential AMs-based approach contributed to revealing the PKAR Storage & Stability dynamic evolution from CHB to cirrhosis and HCC, identifying a panel of genes for the assessment of HCC danger in sufferers with chronic liver illness and may possibly be applied to any time-dependent cancer danger prediction.Abbreviations AMs: Allosteric modules; AUC: Location beneath the curve; CHB: Chronic hepatitis B; CAMs: Conserved allosteric modules; DEMs: Disease-exclusive modules; LIHC: Liver hepatocellular carcinoma; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; MP: Modular pharmacology; OAMs: Oncogenic allosteric modules; OOB: Out-of-bag; ROC curve: Receiver operating characteristic curve; TCGA: The Cancer Genome Atlas; TAMs: Transitional allosteric modules.DeclarationsEthics approval and consent to participate The study was approved by the Official Ethics Committee on the Shanghai University of Traditional Chinese Medicine, and written informed consent was obtained from all study participants. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details 1 Guang’anmen Hospital, China Ac.