RECONSTRUCTION OF GENE AND ASSOCIATIVE NETWORKS OF DISEASES TO SEARCH FOR TARGET GENES
Abstract and keywords
Abstract (English):
Computer reconstruction of gene networks—sets of interacting macromolecules with common functions – is a complex task in bioinformatics. Gene networks, presented as graphical structures, offer a convenient means of visualization and provide qualitatively new insights into the set of studied genes and their biological functions. Expanding further, we explore associative gene networks related to diseases. These networks encompass not only genes and their products (proteins, metabolites, non-coding RNA and drug compounds) but also common disease indicators (symptoms, phenotypic manifestations). Software tools aimed at reconstructing gene network graphs are undergoing active development worldwide and find significant utility in biomedicine. We evaluate available online bioinformatics tools for gene network reconstruction based on gene lists and corresponding computer analysis pipelines. We delve into examples showcasing the utilization of online programs for analyzing the glioma gene network. The proposed approach can be extended to other functional gene sets linked to diseases. Scrutinizing the structure of disease-associated gene networks enables the identification of pivotal genes, which can serve as therapeutic targets. Employing similar bioinformatics strategies, gene networks of intricate disorders such as Parkinson's disease, dementia, schizophrenia, breast cancer, and other cancers have been explored. We delve into the applications of computer programs for gene network analysis and address pedagogical aspects of the field.

Keywords:
bioinformatics, gene networks, glioma, complex diseases, protein-protein interactions, medical informatics
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References

1. Dokhoyan A.Y., Glushchenko M.V., Orlov Y.L. Reconstruction of schizophrenia gene network to search for target genes. Ulyanovsk Medical Biological Journal, 2022, vol. 3, pp. 6-22 (In Russ.).

2. Gubanova N.V., Orlova N.G., Dergilev A.I., Oparina N.Y., Orlov Y.L. Glioblastoma gene network reconstruction and ontology analysis by online bioinformatics tools. Journal of Integrative Bioinformatics, 2021, vol. 18, p. 20210031, doi:https://doi.org/10.1515/jib-2021-0031.

3. Turkina V.A., Maiorova A.A., Dergilev A.I., Krasilnikova A.A., Lanskikh D.V., Kumeiko V.V., Orlov Yu.L. Computer analysis of the structure of the gene network of glioblastoma and brain tumors. Collection of scientific papers of the VII Congress of Biophysicists of Russia: in 2 volumes, vol. 1 - Krasnodar: Printing house of FGBOU VO "KubGTU", 2023, pp. 294-295 (In Russ.).

4. Anashkina A.A., Leberfarb E.Y., Orlov Y.L. Recent Trends in Cancer Genomics and Bioinformatics Tools Development. International Journal of Molecular Sciences, 2021, vol. 22, p. 12146, doi:https://doi.org/10.3390/ijms222212146.

5. Klimontov V.V., Koshechkin K.A., Orlova N.G., Sekacheva M.I., Orlov Y.L. Medical Genetics, Genomics and Bioinformatics-2022. International Journal of Molecular Sciences, 2023, vol. 24, no. 10, p. 8968, doi:https://doi.org/10.3390/ijms24108968.

6. Demenkov P.S., Ivanisenko T.V., Kolchanov N.A., Ivanisenko V.A. ANDVisio: a new tool for graphic visualization and analysis of literature mined associative gene networks in the ANDSystem. In Silico Biol., 2011, vol. 11, no. 3-4, pp. 149-161, doi:https://doi.org/10.3233/ISB-2012-0449.

7. Ivanisenko T.V., Saik O.V., Demenkov P.S., Ivanisenko N.V., Savostianov A.N., Ivanisenko V.A. ANDDigest: a new web-based module of ANDSystem for the search of knowledge in the scientific literature. BMC Bioinformatics, 2020, vol. 21, suppl. 11, p. 228, doi:https://doi.org/10.1186/s12859-020-03557-8.

8. Ivanisenko V.A., Saik O.V., Ivanisenko N.V. et al. ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Syst Biol., 2015, vol. 9, suppl. 2, p. S2, doi:https://doi.org/10.1186/1752-0509-9-S2-S2.

9. Orlov Y.L., Shaderkin I.A., Orlova N.G., Ryabkov I.V., Lebedev G.S. Digitalization of Medical Education and Telemedicine. Physico-Chemical Methods in Interdisciplinary Environmental Research. All-Russian Symposium and School-Conference of Young Scientists, October 27 - November 3, 2021, Sevastopol, Russia. Symposium Proceedings. Moscow: "Granitsa" Publishing House, 2021, pp. 340-341 (In Russ.).

10. Orlova N.G., Orlov Y.L. Problems of developing online training courses for students in digital disciplines using bioinformatics as an example. In: Proceedings of the International Conference “Scientific research of the SCO countries: synergy and integration”. Scientific publishing house Infinity, 2022, pp. 58-65.

11. Orlov Y.L., Anashkina A.A., Ryabkov I.V., Lisnenko A.A., Lebedev G.S. Digitalization of Medical Education: Remote Teaching of Bioinformatics and Scientific Research Using Internet Technologies. Science in the Innovative Process: Proceedings of the International Scientific and Practical Conference (Moscow, December 1–2, 2021). Moscow: IPHRAS RAS, 2021, pp. 222-226 (In Russ.).

12. Orlov Y.L., Galieva A.G., Orlova N.G., Ivanova E.N., Mozylova Y.A., Anashkina A.A. Reconstruction of the Parkinson's disease gene network for target gene identification. Biomedical Chemistry, 2021, vol. 67, iss. 3, pp. 222-230 (In Russ.).

13. Tiis R.P., Osipova L.P., Galieva E.R., Lichman D.V., Voronina E.N., Melikhova A.V., Orlov Y.L., Filipenko M.L. Polymorphism of N-acetyltransferase 2 (NAT2) gene variants and gene network analysis. Biomedicinskaya himiya, 2021, vol. 67, no. 3, pp. 213-221 (In Russ.).

14. Osborn A.G., Louis D.N., Poussaint T.Y., Linscott L.L., Salzman K.L. The 2021 World Health Organization Classification of Tumors of the Central Nervous System: What Neuroradiologists Need to Know. AJNR Am. J. Neuroradiol., 2022, vol. 43, no. 7, pp. 928-937, doi:https://doi.org/10.3174/ajnr.A7462.

15. Byun Y.H., Park C.-K. Classification and Diagnosis of Adult Glioma: A Scoping Review. Brain & Neurorehabilitation. Korean Society for Neurorehabilitation, 2022, vol. 15, no. 3, pp. 3-5.

16. Chang S., Yim S., Park H. The cancer driver genes IDH1/2, JARID1C/ KDM5C, and UTX/ KDM6A: crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism. Exp Mol Med., 2019, vol. 51, no. 6, pp. 1-17, doi:https://doi.org/10.1038/s12276-019-0230-6.

17. Qi S., Yu L., Li H. et al. Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol Lett., 2014, vol. 7, no. 6, pp. 1895-1902, doi:https://doi.org/10.3892/ol.2014.2013.

18. Carrillo J.A., Lai A., Nghiemphu P.L. et al. Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma. AJNR Am J Neuroradiol., 2012, vol. 33, no. 7, pp. 1349-1355, doi:https://doi.org/10.3174/ajnr.A2950.

19. Gritsch S., Batchelor T.T., Gonzalez Castro L.N. Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer, 2022, vol. 128, no. 1, pp. 47-58, doi:https://doi.org/10.1002/cncr.33918.

20. Voropaeva E.N., Pospelova T.I., Orlov Y.L., Churkina M.I., Berezina O.V., Gurazheva A.A., Ageeva T.A., Seregina O.B., Maksimov V.N. The Methylation of the p53 Targets the Genes MIR-203, MIR-129-2, MIR-34A and MIR-34B/C in the Tumor Tissue of Diffuse Large B-Cell Lymphoma. Genes, 2022, vol. 13, no. 8, p. 1401, doi:https://doi.org/10.3390/genes13081401.

21. Konovalov N.A., Vasyutin D.S., Shaikhaev E.G., Kaprov S.V., Timonin S.Yu. Molecular biomarkers of astrocytomas of the brain and spinal cord. Acta Naturae, 2019, vol. 11, vol. 2, no. 41, pp. 17-27 (In Russ.).

22. Pushkin A.A., Timoshkina N.N., Rostorguev E.E. Expression status of 15 genes in glial tumors of the brain. Research Practical Medicine Journal, vol. 6, no. Special issue, 2019, p. 230 (In Russ.).

23. Davis M.E. Epidemiology and Overview of Gliomas. Semin. Oncol. Nurs., 2018, vol. 34, no. 5, pp. 420-429, doi:https://doi.org/10.1016/j.soncn.2018.10.001.

24. Stelzer G., Rosen N., Plaschkes I. et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics, 2016, vol. 54, pp. 1.30.1-1.30.33, doi:https://doi.org/10.1002/cpbi.5.

25. Aleksander S.A, Balhoff J. et al. The Gene Ontology Consortium, The Gene Ontology knowledgebase in 2023. Genetics, 2023, vol. 224, no. 1, iyad031, pp. 2-12, doi:https://doi.org/10.1093/genetics/iyad031.

26. Voropaeva E.N., Pospelova T.I., Voevoda M.I., Maksimov V.N., Orlov Y.L., Seregina O.B. Clinical aspects of TP53 gene inactivation in diffuse large B-cell lymphoma. BMC Med Genomics, 2019, vol. 12, suppl. 2, pp. 35, doi:https://doi.org/10.1186/s12920-019-0484-9.

27. Xu Y., Tong X., Yan J., Wu X., Shao Y.W., Fan Y. Short-Term Responders of Non–Small Cell Lung Cancer Patients to EGFR Tyrosine Kinase Inhibitors Display High Prevalence of TP53 Mutations and Primary Resistance Mechanisms. Transl. Oncol., 2018, vol. 11, no. 6, pp. 1364-1369, doi:https://doi.org/10.1016/j.tranon.2018.08.010.

28. Pobyarzhin V.V. Changes in TP53 suppressor gene expression in rat tissues in experimental ascariasis at different observation periods during reproduction of the rat glioma C6 tumor model in situ. International research journal, 2022, vol. 9, no. 123, p. 1 (In Russ.).

29. Tran P.M.H., Tran L.K.H., Satter K.B., Purohit S., Nechtman J., Hopkins D.I., Dos Santos B., Bollag R., Kolhe R., Sharma S., She J.X. Retrospective Validation of a 168-Gene Expression Signature for Glioma Classification on a Single Molecule Counting Platform. Cancers (Basel), 2021, vol. 13, no. 3, p. 439, doi:https://doi.org/10.3390/cancers13030439.

30. Cohen S. Isolation of a Mouse Submaxillary Gland Protein Accelerating Incisor Eruption and Eyelid Opening in the New-born Animal. J. Biol. Chem., 1962, vol. 237, no. 6, pp. 1555-1562.

31. Levi-Montalcini R., Booker B. Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands. Proc. Natl. Acad. Sci. U.S.A., 1960, vol. 46, no. 3, p. 373.

32. Tan S., Spear R., Zhao J., Sun X., Wang P. Comprehensive Characterization of a Novel E3-Related Gene Signature with Implications in Prognosis and Immunotherapy of Low-Grade Gliomas. Front Genet., 2022, vol. 13, p. 905047, doi:https://doi.org/10.3389/fgene.2022.905047.

33. Wen J., Zhao W., Shu X. A novel cuproptosis-related LncRNA signature: Prognostic and therapeutic value for low grade glioma. Front. Oncol., 2023, vol. 12, p. 1087762, doi:https://doi.org/10.3389/fonc.2022.1087762.

34. Xie J., Sun J., Feng J., Yang F., Wang J., Wen T., Nie Q. Kernel Differential Subgraph Analysis to Reveal the Key Period Affecting Glioblastoma. Biomolecules, 2020, vol. 318, doi:https://doi.org/10.3390/biom10020318.

35. Zhao B.-W., Su X.-R., Hu P.-W., Huang Y.-A., You Z.-H., Hu L. iGRLDTI: an improved graph representation learning method for predicting drug-target interactions over heterogeneous biological information network. Bioinformatics, 2023, vol. 39, no. 8, p. 2, btad45, doi:https://doi.org/10.1093/bioinformatics/btad451.

36. Babenko V.N., Gubanova N.V., Bragin A.O., Chadaeva I.V., Vasiliev G.V., Medvedeva I.V., Gaytan A.S., Krivoshapkin A.L., Orlov Y.L. Computer Analysis of Glioma Transcriptome Profiling: Alternative Splicing Events. Journal of Integrative Bioinformatics, 2017, vol. 14, no. 3, p. 20170022, doi:https://doi.org/10.1515/jib-2017-0022.

37. Babenko V.N., Bragin A.O., Spitsina A.M., Chadaeva I.V., Galieva E.R., Orlova G.V., Medvedeva I.V., Orlov Y.L. Analysis of differential gene expression by RNA-seq data in brain areas of laboratory animals. Journal of Integrative Bioinformatics, 2016, vol. 13, no. 4, pp. 292, doi:https://doi.org/10.2390/biecoll-jib-2016-292.

38. Ivanisenko T.V., Demenkov P.S., Kolchanov N.A., Ivanisenko V.A. The New Version of the ANDDigest Tool with Improved AI-Based Short Names Recognition. Int J Mol Sci., 2022, vol. 23, no. 23, p. 14934, doi:https://doi.org/10.3390/ijms232314934.

39. Khlebodarova T.M., Demenkov P.S., Ivanisenko T.V., Antropova E.A., Lavrik I.N., Ivanisenko V.A. Primary and Secondary micro-RNA Modulation the Extrinsic Pathway of Apoptosis in Hepatocellular Carcinoma. Mol. Biol. (Mosk), 2023, vol. 57, no. 2, pp. 165-175, doi:https://doi.org/10.1134/S0026893323020103.

40. Brix T.J., Berentzen M., Becker L., Storck M., Varghese J. Development of a Command Line Interface for the Analysis of Result Sets from Automated Queries to Literature Databases. Stud Health Technol Inform., 2023, vol. 302, pp. 162-166, doi:https://doi.org/10.3233/SHTI230095.

41. Lu Z. PubMed and beyond: a survey of web tools for searching biomedical literature. Database (Oxford), 2011, vol. 2011, baq036, pp. 1-12, doi:https://doi.org/10.1093/database/baq036.

42. Veljkovic A.N., Orlov Y.L., Mitic N.S. BioGraph: Data Model for Linking and Querying Diverse Biological Metadata. International Journal of Molecular Sciences, 2023, vol. 24, no. 8, p. 6954, doi:https://doi.org/10.3390/ijms24086954.

43. Orlov Y.L., Baranova A.V. Editorial: Bioinformatics of Genome Regulation and Systems Biology. Front Genet., 2020, vol. 11, pp. 625, doi:https://doi.org/10.3389/fgene.2020.00625.

44. Orlov Y.L., Hofestaedt R.M., Kolchanov N.A. Introductory note for BGRS\SB-2014 special issue. J. Bioinform. Comput. Biol., 2015, vol. 13, no. 1, p. 1502001, doi:https://doi.org/10.1142/S0219720015020011.

45. Dergilev A.I., Orlova N.G., Dobrovolskaya O.B., Orlov Y.L. Statistical estimates of multiple transcription factors binding in the model plant genomes based on ChIP-seq data. Journal of Integrative Bioinformatics, 2021, vol. 19, no. 1, p. 20200036, doi:https://doi.org/10.1515/jib-2020-0036.

46. Orlov Y., Dobrovolskaya O., Chen M., Hofestadt R. Bioinformatics of genome regulation and structure – 2020 papers collection. Journal of Integrative Bioinformatics, 2020 vol. 17, no. 4, p. 20200038, doi:https://doi.org/10.1515/jib-2020-0038.

47. Karpov O.E., Klimenko G.S., Lebedev G.S. Application of intelligent systems in healthcare. Modern high technologies, 2016, vol. 7, pp. 38-43 (In Russ.).

48. Lebedev G., Polikarpov A., Golubev N., Tyurina E., Serikov A., Selivanov D., Orlov Y. The Geographic Information System of the Russian Ministry of Health. In: Czarnowski I., Howlett R., Jain L. (eds) Intelligent Decision Technologies. IDT 2020. Smart Innovation, Systems and Technologies, 2020, vol. 193, pp. 403-411. Springer, Singapore, doi:https://doi.org/10.1007/978-981-15-5925-9_34.

49. Xing X., Yang F., Li H. et al. Multi-level attention graph neural network based on co-expression gene modules for disease diagnosis and prognosis. Bioinformatics, 2022, vol. 38, no. 8, pp. 1-6, 2178-2186, doi:https://doi.org/10.1093/bioinformatics/btac088.

50. Oloulade B.M., Gao J., Chen J., Al-Sabri R., Wu Z. Cancer Drug Response Prediction with Surrogate Modeling-Based Graph Neural Architecture Search. Bioinformatics, 2023, btad478, doi:https://doi.org/10.1093/bioinformatics/btad478.


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