Current Gene TherapyCurrent Gene TherapyCurrent Gene Therapy1566-52321875-5631Bentham Science64400310.2174/0115665232268074231026111634Life SciencesResearch ArticlePrediction of SARS-CoV-2 Infection Phosphorylation Sites and Associations of these Modifications with Lung Cancer DevelopmentLiWeiinfo@benthamscience.netLiGeninfo@benthamscience.netSunYuzhiinfo@benthamscience.netZhangLiyuaninfo@benthamscience.netCuiXinraninfo@benthamscience.netJiaYuraninfo@benthamscience.netZhaoTianyiinfo@benthamscience.netInstitute of Bioinformatics, Harbin Institute of TechnologyDepartment of Radiation Oncology, Harbin Medical University Cancer HospitalInstitute for Bioinformatics, School of Computer Science and Technology, Harbin Institute of TechnologyInstitute for Bioinformatics, School of Computer Science and Technology,, Harbin Institute of TechnologySchool of Medicine and Health, Harbin Institute of Technology0103202424323924807012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://transsyst.ru/1566-5232/article/view/644003

Introduction:Since the emergence of SARS-CoV-2 viruses, multiple mutant strains have been identified. Infection with SARS-CoV-2 virus leads to alterations in host cell phosphorylation signal, which systematically modulates the immune response.

Methods:Identification and analysis of SARS-CoV-2 virus infection phosphorylation sites enable insight into the mechanisms of viral infection and effects on host cells, providing important fundamental data for the study and development of potent drugs for the treatment of immune inflammatory diseases. In this paper, we have analyzed the SARS-CoV-2 virus-infected phosphorylation region and developed a transformer-based deep learning-assisted identification method for the specific identification of phosphorylation sites in SARS-CoV-2 virus-infected host cells.

Results:Furthermore, through association analysis with lung cancer, we found that SARS-CoV-2 infection may affect the regulatory role of the immune system, leading to an abnormal increase or decrease in the immune inflammatory response, which may be associated with the development and progression of cancer.

Conclusion:We anticipate that this study will provide an important reference for SARS-CoV-2 virus evolution as well as immune-related studies and provide a reliable complementary screening tool for anti-SARS-CoV-2 virus drug and vaccine design.

Deep learninglung cancerphosphorylationSARS-CoV-2transformerimmune inflammatory diseases.Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020; 26(6): 845-8. doi: 10.1038/s41591-020-0897-1 PMID: 32350462Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020; 181(2): 281-292.e6. doi: 10.1016/j.cell.2020.02.058 PMID: 32155444Stukalov A, Girault V, Grass V, et al. Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 2021; 594(7862): 246-52. doi: 10.1038/s41586-021-03493-4 PMID: 33845483Thorne LG, Bouhaddou M, Reuschl AK, et al. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature 2022; 602(7897): 487-95. doi: 10.1038/s41586-021-04352-y PMID: 34942634Lamers MM, Beumer J, Van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020; 369(6499): 50-4. doi: 10.1126/science.abc1669 PMID: 32358202Chen DY, Khan N, Close BJ, et al. SARS-CoV-2 disrupts proximal elements in the JAK-STAT pathway. J Virol 2021; 95(19): e00862-21. doi: 10.1128/JVI.00862-21 PMID: 34260266Sharma A, Garcia G Jr, Wang Y, et al. Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infection. Cell Rep Med 2020; 1(4): 100052. doi: 10.1016/j.xcrm.2020.100052 PMID: 32835305Liu JF, Peng WJ, Wu Y, et al. Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice. EBioMedicine 2023; 90: 104518. doi: 10.1016/j.ebiom.2023.104518 PMID: 36933413Shemesh M, Aktepe TE, Deerain JM, et al. SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon. PLoS Pathog 2021; 17(8): e1009800. doi: 10.1371/journal.ppat.1009800 PMID: 34437657Bouhaddou M, Memon D, Meyer B, et al. The global phosphorylation landscape of SARS-CoV-2 infection. Cell 2020; 182(3): 685-712.e19. doi: 10.1016/j.cell.2020.06.034 PMID: 32645325Klann K, Bojkova D, Tascher G, Ciesek S, Münch C, Cinatl J. Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication. Mol Cell 2020; 80(1): 164-174.e4. doi: 10.1016/j.molcel.2020.08.006 PMID: 32877642Gao J, Thelen JJ, Dunker AK, Xu D. Musite, a tool for global prediction of general and kinase-specific phosphorylation sites. Mol Cell Proteomics 2010; 9(12): 2586-600. doi: 10.1074/mcp.M110.001388 PMID: 20702892Li F, Li C, Marquez-Lago TT, et al. Quokka: A comprehensive tool for rapid and accurate prediction of kinase family-specific phosphorylation sites in the human proteome. Bioinformatics 2018; 34(24): 4223-31. doi: 10.1093/bioinformatics/bty522 PMID: 29947803Liu Q, Luo X, Li J, Wang G. scESI: evolutionary sparse imputation for single-cell transcriptomes from nearest neighbor cells. Brief Bioinform 2022; 23(5): bbac144. doi: 10.1093/bib/bbac144 PMID: 35512331Liu Q, Zhao X, Wang G. A clustering ensemble method for cell type detection by multiobjective particle optimization. IEEE/ACM Trans Comput Biol Bioinformatics 2023; 20(1): 1-14. PMID: 34860653Wang D, Zeng S, Xu C, et al. MusiteDeep: A deep-learning framework for general and kinase-specific phosphorylation site prediction. Bioinformatics 2017; 33(24): 3909-16. doi: 10.1093/bioinformatics/btx496 PMID: 29036382Guo L, Wang Y, Xu X, et al. DeepPSP: A global–local information-based deep neural network for the prediction of protein phosphorylation sites. J Proteome Res 2021; 20(1): 346-56. doi: 10.1021/acs.jproteome.0c00431 PMID: 33241931Lv H, Dao FY, Zulfiqar H, Lin H. DeepIPs: Comprehensive assessment and computational identification of phosphorylation sites of SARS-CoV-2 infection using a deep learning-based approach. Brief Bioinform 2021; 22(6): bbab244. doi: 10.1093/bib/bbab244 PMID: 34184738Stukalov A, Girault V, Grass V, et al. Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV. bioRxiv 2020.Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22(13): 1658-9. doi: 10.1093/bioinformatics/btl158 PMID: 16731699Vaswani A, Shazeer N, Parmar N, et al. Polosukhin IJa. Attention Is All You Need. In: Advances in neural information processing. 2017; p. 30.Li Z, Jin J, Wang Y, et al. ExamPle: Explainable deep learning framework for the prediction of plant small secreted peptides. Bioinformatics 2023; 39(3): btad108. doi: 10.1093/bioinformatics/btad108 PMID: 36897030Charoenkwan P, Nantasenamat C, Hasan MM, Manavalan B, Shoombuatong W. BERT4Bitter: A bidirectional encoder representations from transformers (BERT)-based model for improving the prediction of bitter peptides. Bioinformatics 2021; 37(17): 2556-62. doi: 10.1093/bioinformatics/btab133 PMID: 33638635Ji Y, Zhou Z, Liu H, Davuluri RV. DNABERT: pre-trained bidirectional encoder representations from transformers model for dna-language in genome. Bioinformatics 2021; 37(15): 2112-20. doi: 10.1093/bioinformatics/btab083 PMID: 33538820Nie L, Quan L, Wu T, He R, Lyu Q. TransPPMP: Predicting pathogenicity of frameshift and non-sense mutations by a transformer based on protein features. Bioinformatics 2022; 38(10): 2705-11. doi: 10.1093/bioinformatics/btac188 PMID: 35561183Cho K, van Merrienboer B, Gulcehre C, et al. Learning phrase representations using RNN encoder-decoder for statistical machine translation. Arxiv 2014. doi: 10.3115/v1/D14-1179Jia Y, Huang S, Zhang TKK-DBP. A multi-feature fusion method for dna-binding protein identification based on random forest. Front Genet 2021; 12: 811158. doi: 10.3389/fgene.2021.811158 PMID: 34912382Zhang T, Jia Y, Li H, Xu D, Zhou J, Wang G. CRISPRCasStack: A stacking strategy-based ensemble learning framework for accurate identification of Cas proteins. Brief Bioinform 2022; 23(5): bbac335. doi: 10.1093/bib/bbac335 PMID: 35998924Ardito F, Giuliani M, Perrone D, Troiano G, Muzio LL. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med 2017; 40(2): 271-80. doi: 10.3892/ijmm.2017.3036 PMID: 28656226Ashton TM, McKenna WG, Kunz-Schughart LA, Higgins GS. Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res 2018; 24(11): 2482-90. doi: 10.1158/1078-0432.CCR-17-3070 PMID: 29420223