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Integrating Molecular Perspectives: Strategies for Comprehensive Multi-Omics Integrative Data Analysis and Machine Learning Applications in Transcriptomics, Proteomics, and Metabolomics

Pedro H. Godoy Sanches, Nicolly Clemente de Melo, Andreia M. Porcari and 1 more

Biology · 2024 · Review · CC BY

doi:10.3390/biology13110848

Abstract

Simple Summary. Recent high-throughput technologies such as transcriptomics, proteomics, and metabolomics have allowed progress in understanding biological systems at different levels of detail. Even so, it is necessary to integrate multiple omics data sets to achieve a comprehensive understanding of the subject under study. In this article, we review the methods used for integrating transcriptomics, proteomics, and metabolomics data and summarize them in three approaches: combined omics integration, correlation-based integration strategies, and machine learning integrative approaches. Our goal is to showcase the uses and limitations of each approach, allowing researchers to choose the more appropriate tool for each scenario to extract a comprehensive view of a biological system.

Abstract. With the advent of high-throughput technologies, the field of omics has made significant strides in characterizing biological systems at various levels of complexity. Transcriptomics, proteomics, and metabolomics are the three most widely used omics technologies, each providing unique insights into different layers of a biological system. However, analyzing each omics data set separately may not provide a comprehensive understanding of the subject under study. Therefore, integrating multi-omics data has become increasingly important in bioinformatics research. In this article, we review strategies for integrating transcriptomics, proteomics, and metabolomics data, including co-expression analysis, metabolite–gene networks, constraint-based models, pathway enrichment analysis, and interactome analysis. We discuss combined omics integration approaches, correlation-based strategies, and machine learning techniques that utilize one or more types of omics data. By presenting these methods, we aim to provide researchers with a better understanding of how to integrate omics data to gain a more comprehensive view of a biological system, facilitating the identification of complex patterns and interactions that might be missed by single-omics analyses.

References 158

  1. 1.
  2. 2.

    Hasanzad M., Sarhangi N., Ehsani Chimeh S., Ayati N., Afzali M., Khatami F., Nikfar S., Aghaei Meybodi H.R. Precision Medicine Journey through Omics Approach. J. Diabetes Metab. Disord. 2022;21:881-888.

    Not in our library10.1007/s40200-021-00913-0

  3. 3.

    Karczewski K.J., Snyder M.P. Integrative Omics for Health and Disease. Nat. Rev. Genet. 2018;19:299-310.

    Not in our library10.1038/nrg.2018.4

  4. 4.

    Picard M., Scott-Boyer M.P., Bodein A., Périn O., Droit A. Integration Strategies of Multi-Omics Data for Machine Learning Analysis. Comput. Struct. Biotechnol. J. 2021;19:3735-3746.

    Not in our library10.1016/j.csbj.2021.06.030

  5. 5.

    Rozanova S., Barkovits K., Nikolov M., Schmidt C., Urlaub H., Marcus K. Quantitative Mass Spectrometry-Based Proteomics: An Overview. Methods Mol. Biol. 2021;2228:85-116.

    Not in our library10.1007/978-1-0716-1024-4_8

  6. 6.

    Reel P.S., Reel S., Pearson E., Trucco E., Jefferson E. Using Machine Learning Approaches for Multi-Omics Data Analysis: A Review. Biotechnol. Adv. 2021;49:107739.

    Not in our library10.1016/j.biotechadv.2021.107739

  7. 7.

    de Carvalho L.M., Borelli G., Camargo A.P., de Assis M.A., de Ferraz S.M.F., Fiamenghi M.B., José J., Mofatto L.S., Nagamatsu S.T., Persinoti G.F., et al. Bioinformatics Applied to Biotechnology: A Review towards Bioenergy Research. Biomass Bioenergy. 2019;123:195-224.

    Not in our library10.1016/j.biombioe.2019.02.016

  8. 8.

    Wang R., Li B., Lam S.M., Shui G. Integration of Lipidomics and Metabolomics for In-Depth Understanding of Cellular Mechanism and Disease Progression. J. Genet. Genom. 2020;47:69-83.

    Not in our library10.1016/j.jgg.2019.11.009

  9. 9.

    Idle J.R., Gonzalez F.J. Metabolomics. Cell Metab. 2007;6:348-351.

    Not in our library10.1016/j.cmet.2007.10.005

  10. 10.

    Athieniti E., Spyrou G.M. A Guide to Multi-Omics Data Collection and Integration for Translational Medicine. Comput. Struct. Biotechnol. J. 2023;21:134-149.

    Not in our library10.1016/j.csbj.2022.11.050

  11. 11.

    Budzinski I.G.F., de Moraes F.E., Cataldi T.R., Franceschini L.M., Labate C.A. Network Analyses and Data Integration of Proteomics and Metabolomics from Leaves of Two Contrasting Varieties of Sugarcane in Response to Drought. Front. Plant Sci. 2019;10:446557.

    Not in our library10.3389/fpls.2019.01524

  12. 12.

    Dimitrakopoulos C., Hindupur S.K., Hafliger L., Behr J., Montazeri H., Hall M.N., Beerenwinkel N. Network-Based Integration of Multi-Omics Data for Prioritizing Cancer Genes. Bioinformatics. 2018;34:2441-2448.

    Not in our library10.1093/bioinformatics/bty148

  13. 13.

    Misra B.B., Langefeld C., Olivier M., Cox L.A. Integrated Omics: Tools, Advances and Future Approaches. J. Mol. Endocrinol. 2019;62:R21-R45.

    Not in our library10.1530/jme-18-0055

  14. 14.

    Cambiaghi A., Ferrario M., Masseroli M. Analysis of Metabolomic Data: Tools, Current Strategies and Future Challenges for Omics Data Integration. Brief. Bioinform. 2017;18:498-510.

    Not in our library10.1093/bib/bbw031

  15. 15.
  16. 16.

    Fukushima A., Kusano M., Redestig H., Arita M., Saito K. Integrated Omics Approaches in Plant Systems Biology. Curr. Opin. Chem. Biol. 2009;13:532-538.

    Not in our library10.1016/j.cbpa.2009.09.022

  17. 17.

    Hrovatin K., Fischer D.S., Theis F.J. Toward Modeling Metabolic State from Single-Cell Transcriptomics. Mol. Metab. 2022;57:101396.

    Not in our library10.1016/j.molmet.2021.101396

  18. 18.

    Sun Y., Liu Z., Fu Y., Yang Y., Lu J., Pan M., Wen T., Xie X., Bai Y., Ge Q. Single-Cell Multi-Omics Sequencing and Its Application in Tumor Heterogeneity. Brief. Funct. Genom. 2023;22:313-328.

    Not in our library10.1093/bfgp/elad009

  19. 19.

    Dimitriu M.A., Lazar-Contes I., Roszkowski M., Mansuy I.M. Single-Cell Multiomics Techniques: From Conception to Applications. Front. Cell Dev. Biol. 2022;10:854317.

    Not in our library10.3389/fcell.2022.854317

  20. 20.

    Flynn E., Almonte-Loya A., Fragiadakis G.K. Single-cell multiomics. Annu. Rev. Biomed. Data Sci. 2023;6:313-337.

    Not in our library10.1146/annurev-biodatasci-020422-050645

  21. 21.

    Adossa N., Khan S., Rytkönen K.T., Elo L.L. Computational Strategies for Single-Cell Multi-Omics Integration. Comput. Struct. Biotechnol. J. 2021;19:2588-2596.

    Not in our library10.1016/j.csbj.2021.04.060

  22. 22.

    Baysoy A., Bai Z., Satija R., Fan R. The Technological Landscape and Applications of Single-Cell Multi-Omics. Nat. Rev. Mol. Cell Biol. 2023;24:695-713.

    Not in our library10.1038/s41580-023-00615-w

  23. 23.

    Chen G., Yu R., Chen X. Editorial: Integrative Analysis of Single-Cell and/or Bulk Multi-Omics Sequencing Data. Front. Genet. 2023;13:1121999.

    Not in our library10.3389/fgene.2022.1121999

  24. 24.

    Huang Y., Mohanty V., Dede M., Tsai K., Daher M., Li L., Rezvani K., Chen K. Characterizing Cancer Metabolism from Bulk and Single-Cell RNA-Seq Data Using METAFlux. Nat. Commun. 2023;14:4883.

    Not in our library10.1038/s41467-023-40457-w

  25. 25.
  26. 26.
  27. 27.

    Zeng F., Shi M., Xiao H., Chi X. WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease. BioMed Res. Int. 2021;2021:5633211.

    Not in our library10.1155/2021/5633211

  28. 28.

    Choi H., Na K.J. Integrative Analysis of Imaging and Transcriptomic Data of the Immune Landscape Associated with Tumor Metabolism in Lung Adenocarcinoma: Clinical and Prognostic Implications. Theranostics. 2018;8:1956-1965.

    Not in our library10.7150/thno.23767

  29. 29.

    Liu P., Luo J., Zheng Q., Chen Q., Zhai N., Xu S., Xu Y., Jin L., Xu G., Lu X., et al. Integrating Transcriptome and Metabolome Reveals Molecular Networks Involved in Genetic and Environmental Variation in Tobacco. DNA Res. 2020;27:dsaa006.

    Not in our library10.1093/dnares/dsaa006

  30. 30.

    Amiri F., Moghadam A., Tahmasebi A., Niazi A. Identification of Key Genes Involved in Secondary Metabolite Biosynthesis in Digitalis Purpurea. PLoS ONE. 2023;18:e0277293.

    Not in our library10.1371/journal.pone.0277293

  31. 31.

    Moghadam A., Foroozan E., Tahmasebi A., Taghizadeh M.S., Bolhassani M., Jafari M. System Network Analysis of Rosmarinus Officinalis Transcriptome and Metabolome—Key Genes in Biosynthesis of Secondary Metabolites. PLoS ONE. 2023;18:e0282316.

    Not in our library10.1371/journal.pone.0282316

  32. 32.

    Ponsuksili S., Trakooljul N., Hadlich F., Methling K., Lalk M., Murani E., Wimmers K. Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters. Front. Genet. 2019;10:419414.

    Not in our library10.3389/fgene.2019.00348

  33. 33.

    Zhu Y., Mordaunt C.E., Durbin-Johnson B.P., Caudill M.A., Malysheva O.V., Miller J.W., Green R., James S.J., Melnyk S.B., Fallin M.D., et al. Expression Changes in Epigenetic Gene Pathways Associated with One-Carbon Nutritional Metabolites in Maternal Blood from Pregnancies Resulting in Autism and Non-Typical Neurodevelopment. Autism Res. 2021;14:11-28.

    Not in our library10.1002/aur.2428

  34. 34.

    Hoang L.T., Domingo-Sabugo C., Starren E.S., Willis-Owen S.A.G., Morris-Rosendahl D.J., Nicholson A.G., Cookson W.O.C.M., Moffatt M.F. Metabolomic, Transcriptomic and Genetic Integrative Analysis Reveals Important Roles of Adenosine Diphosphate in Haemostasis and Platelet Activation in Non-Small-Cell Lung Cancer. Mol. Oncol. 2019;13:2406-2421.

    Not in our library10.1002/1878-0261.12568

  35. 35.

    Wang Z., Zhang X., He S., Rehman A., Jia Y., Li H., Pan Z., Geng X., Gao Q., Wang L., et al. Transcriptome Co-Expression Network and Metabolome Analysis Identifies Key Genes and Regulators of Proanthocyanidins Biosynthesis in Brown Cotton. Front. Plant Sci. 2022;12:822198.

    Not in our library10.3389/fpls.2021.822198

  36. 36.

    Green R.E., Lord J., Scelsi M.A., Xu J., Wong A., Naomi-James S., Handy A., Gilchrist L., Williams D.M., Parker T.D., et al. Investigating Associations between Blood Metabolites, Later Life Brain Imaging Measures, and Genetic Risk for Alzheimer’s Disease. Alzheimer’s Res. Ther. 2023;15:38.

    Not in our library10.1186/s13195-023-01184-y

  37. 37.

    Green R., Lord J., Xu J., Maddock J., Kim M., Dobson R., Legido-Quigley C., Wong A., Richards M., Proitsi P. Metabolic Correlates of Late Midlife Cognitive Outcomes: Findings from the 1946 British Birth Cohort. Brain Commun. 2022;4:fcab291.

    Not in our library10.1093/braincomms/fcab291

  38. 38.

    Carson C., Lawson H.A. Genetic Background and Diet Affect Brown Adipose Gene Coexpression Networks Associated with Metabolic Phenotypes. Physiol. Genom. 2020;52:223-233.

    Not in our library10.1152/physiolgenomics.00003.2020

  39. 39.

    Zhao X., Ge W., Miao Z. Integrative Metabolomic and Transcriptomic Analyses Reveals the Accumulation Patterns of Key Metabolites Associated with Flavonoids and Terpenoids of Gynostemma pentaphyllum (Thunb.) Makino. Sci. Rep. 2024;14:8644.

    Not in our library10.1038/s41598-024-57716-5

  40. 40.

    Xie Z., Wang J., Wang W., Wang Y., Xu J., Li Z., Zhao X., Fu B. Integrated Analysis of the Transcriptome and Metabolome Revealed the Molecular Mechanisms Underlying the Enhanced Salt Tolerance of Rice Due to the Application of Exogenous Melatonin. Front. Plant Sci. 2021;11:618680.

    Not in our library10.3389/fpls.2020.618680

All 158 references

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