What is Multi-Omics?

Omics, the process of characterizing and quantifying entire sets of biomolecules in an organism, has been a cornerstone in disease research and drug discovery. The benefit of omics transcends large-scale quantification, as researchers can now integrate multiple layers of biological information through multi-omics. Unlike traditional single-omics studies focusing on one type of molecular data, multi-omics enables researchers to examine how genes, proteins and metabolites interact within complex networks.¹

The transition from single-omics to multi-omics marks a major shift in biomedical research. Although scientists initially used to study biomolecules in isolation, advancements in high-throughput technologies and bioinformatics have enabled integrating datasets from several types of macromolecules. By combining diverse omics data, researchers can better understand disease mechanisms and identify novel biomarkers, ultimately accelerating drug discovery and personalized medicine.¹

How Multi-Omics Works

Data Generation

A multi-omics workflow begins with data generation across different omics layers, each providing unique biological insights. ²

• Genomics examines DNA sequences and genetic variations
• Transcriptomics focuses on RNA expression profiles
• Proteomics measures protein abundance and modification states
• Metabolomics identifies small molecules involved in metabolism
• Epigenomics reveals regulatory mechanisms like DNA methylation and histone modification

Advanced high-throughput platforms, such as next-generation sequencing (NGS), mass spectrometry and microarrays, generate these datasets from large sets of biological samples.³ Furthermore, spatial multi-omics explains how various biomolecules are organized within the cell to affect morphology and function.⁴

Data Integration

The multiple omics layers collected from different high-throughput methods must be integrated to reveal meaningful relationships. Integration strategies include statistical, network-based and machine learning approaches that align heterogeneous datasets into a unified framework. Furthermore, data harmonization and normalization methods are employed to reduce noise and ensure comparability. ²

Effective multi-omics data integration allows researchers to uncover molecular interactions and crosstalk between multiple biological pathways. Thus, researchers can link genotype to phenotype and identify key regulatory pathways driving disease or treatment response.²

Molecular Network Analysis

After integration, molecular network analysis helps researchers convert different omics components, e.g., genes, proteins and metabolites, into interactive networks. Computational modeling and systems biology tools map these interactions in graph-based networks, where nodes represent biological entities, while edges depict the pairwise interactions between them. This network-centric approach allows researchers to visualize complex biological processes, highlight regulatory hubs and pathway cross-talks, predict molecular targets and discover potential biomarkers for diagnosis or drug development. Ultimately, molecular network analysis transforms large-scale omics data into actionable biological insights.⁵

Why Multi-Omics Matters in Modern Science

Multi-omics plays a crucial role in advancing our understanding of complex biological systems. Genes or proteins as standalone entities cannot explain complex cellular processes in health and disease. Instead of focusing on isolated genes or proteins, multi-omics allows scientists to study how various biological components interact dynamically to influence health and disease outcomes. This systems-level perspective helps reveal regulatory mechanisms that single-omics studies often overlook.³

Compared to single-layer analysis, multi-omics offers significant advantages, including:³

• Increased data accuracy
• Unbiased data analysis
• A framework for linking genetic variations

Overall, integrating diverse datasets helps identify molecular drivers and interactions that influence disease progression and treatment response. From this perspective, multi-omics has immense potential to improve personalized diagnostics and healthcare. Multi-omics analysis of patient-specific molecular signatures assists early and accurate disease detection and the design of tailored treatments.⁶

Multi-Omics Integration

Multi-omics integration combines data from genomics, transcriptomics, proteomics, metabolomics and epigenomics to obtain a systems-level understanding of biological processes.

Approaches to multi-omics data integration include:

• Computational modeling algorithms that parse diverse datasets into biological networks⁵
• Statistical inference that detects patterns and correlations between molecular layers⁷
• Artificial intelligence (AI) and machine learning techniques for automated feature extraction, clustering, and predictive modeling from high-dimensional data⁸

Nevertheless, integrating multi-omics data comes with significant challenges, such as:⁶

• Handling the sheer volume and dimensionality of omics data
• The lack of data standardization across different high-throughput omics
• The scalability and integrity of multidimensional datasets

Single-Cell Multi-Omics

Some of these challenges can be overcome with single-cell multi-omics, an advanced approach that quantifies multiple molecular layers within individual cells. This technology provides a significant advantage over bulk analysis, which averages measurements across millions of cells, masking cellular heterogeneity.⁹

Heterogeneity is a critical bottleneck in understanding the underlying mechanisms of many diseases, especially cancer. In cancer research, multi-omics is essential for identifying rare tumor and stem cell subpopulations that may promote relapse and drug resistance.¹⁰

Moreover, in rare disease detection, single-cell multi-omics helps pinpoint mutations that occur in only a small subset of cells. This approach allows for patient-specific profiling, facilitating more accurate diagnostics and personalized treatment strategies.¹¹

Compared to traditional single-omics, which analyzes only one molecular layer, single-cell multi-omics incorporates multiple layers from the same cell, offering invaluable insight into complex biological systems.⁹

Applications of Multi-Omics in Drug Discovery

Multi-omics has become an integral part of drug discovery, owing to the holistic understanding of disease biology it engenders.

• Drug discovery and biomarker identification: Multi-omics drives the discovery of molecular markers for drug efficacy and safety, aiding druggable target selection and patient stratification¹²
• Disease mechanism exploration: Researchers gain a deeper understanding of how various molecules and their interactions determine function, phenotype and disease on set¹
• Predictive modeling: Multi-omics data are used to develop computational models that forecast drug responses and adverse effects, providing pharmaceutical companies with the framework to optimize their pipelines for increased clinical trial success¹³
• Biopharmaceutical innovation: Multi-omics contributes to developing precision therapeutics, biologics and combination therapies, driving more effective and safer treatments¹⁴

Benefits of the Multi-Omics Approach in Drug Discovery

Enhanced Drug Target Identification and Validation

The multi-omics approach improves the reliability of target identification and validation by integrating genetic, transcriptomic, proteomic and metabolomic data. This comprehensive view helps support robust validation through evidence from multiple high-throughput datasets, reducing false positives and confirming the biological significance of novel targets.¹²

Understanding of Disease Mechanisms

By linking genetic, transcriptomic, proteomic and metabolic alterations, multi-omics provides a comprehensive view of disease mechanisms. It reveals how molecular pathways interact and how dysregulation at one level reflects on other levels and drives disease. This systems-level understanding informs the development of targeted therapeutic strategies.¹

Improved Biomarker Discovery for Precision Medicine

Multi-omics enhances the efficiency of biomarker discovery by integrating diverse biological signals, leading to more specific and sensitive diagnostic and prognostic indicators. It supports precision medicine by predicting disease risk, treatment response and individual outcomes.¹⁵

Accelerated Drug Development and Reduced Costs

Integrating multi-omics data analysis into drug discovery pipelines accelerates drug development by mediating early-stage target identification and optimization. Omics-driven predictive modeling guides clinical trial design and patient selection, reducing failure rates and overall drug development costs.¹⁶

Facilitation of Drug Repurposing and Combination Therapies

Multi-omics analysis helps uncover shared molecular pathways among different diseases, unveiling opportunities for drug repurposing.¹⁷ It also identifies the interplay between molecular targets and biological networks, informing the design of combination therapies that enhance efficacy and overcome drug resistance. ¹⁸

Tools and Technologies Enabling Multi-Omics

The success of multi-omics research relies on cutting-edge instruments and technologies for generating, integrating and interpreting vast molecular datasets.

Next-gen sequencing, mass spectrometry and imaging advancements have shifted how scientists study biological systems.

• Next-generation sequencing (NGS) technologies improve accuracy and speed in acquiring high-throughput genomic and transcriptomic data¹⁹
• Advancements in mass spectrometry improve speed and precision when identifying and quantifying proteins, peptides and metabolites²⁰
• Advanced imaging techniques, such as spatial omics and single-cell imaging, reveal cellular organization, tissue architecture and interactions in unparalleled detail⁴

At the same time, bioinformatics and computational platforms are crucial for managing and interpreting multi-omics datasets. Statistical inference, machine learning algorithms and network modeling frameworks are powerful tools to extract meaningful insights from heterogeneous data. These tools help deduce correlations between several biological network components and emergent properties.²¹

The role of cloud-based platforms in handling large-scale omics data cannot be overlooked. Cloud infrastructures provide scalable storage, high-performance computing power and data exchange protocols to drive effective collaboration for global research teams. Thus, cloud platforms accelerate multi-omics research and its translation into biomedical and pharmaceutical innovation.²²

Challenges in Multi-Omics Drug Discovery

Despite the evident value of multi-omics in drug discovery, challenges must be addressed to leverage this approach fully.
Combining datasets from different omics layers is challenging due to variations in data types, formats and measurement scales. Heterogeneity across platforms, experimental conditions and sample types can lead to inconsistencies, making accurate integration difficult. Robust data processing algorithms are required to harmonize these diverse datasets, remove redundancies and ensure reliable integration.²³

Interpreting multi-omics data is also challenging because of the incomplete understanding of molecular interactions. Linking genetic, transcriptomic, proteomic and metabolomic changes to biological functions or clinical outcomes requires advanced modeling approaches and deep domain expertise. Without a solid foundation in cell biology, omics data can be misinterpreted, leading to false conclusions.²³

The massive volume of datasets can be computationally intensive to process and analyze. Accurate and interpretable AI algorithms are essential to extract meaningful insights without overfitting or bias.²³

It is also important to note that biological systems are inherently complex and correlations do not suffice to explain causations. Multi-omics research still falls short in capturing the dynamic evolution of biological systems involving oscillations and feedback loops. Therefore, it must be complemented with bottom-up mathematical modeling formalisms. These formalisms allow researchers to formulate biological interactions and biochemical reactions with equations, simulate model behavior and match simulated outcomes to experimental findings to improve accuracy. Overall, combining multi-omics and bottom-up systems biology can drastically improve precision and depth in disease research and drug development.²⁴

References

1. Chen C, Wang J, Pan D, Wang X, Xu Y, Yan J, et al. Applications of multi‐omics analysis in human diseases. MedComm 2023;4(4):e315.
2. Subramanian I, Verma S, Kumar S, Jere A, Anamika K. Multi-omics data integration, interpretation, and application. Bioinform Biol Insights 2020;14:1177932219899051.
3. Hayes CN, Nakahara H, Ono A, Tsuge M, Oka S. From omics to multi-omics: a review of advantages and tradeoffs. Genes 2024;15(12):1551.
4. Vandereyken K, Sifrim A, Thienpont B, Voet T. Methods and applications for single-cell and spatial multi-omics. Nat Rev Genet 2023;24(8):494-515.
5. Agamah FE, Bayjanov JR, Niehues A, Njoku KF, Skelton M, Mazandu GK, et al. Computational approaches for network-based integrative multi-omics analysis. Front Mol Biosci 2022;9:967205.
6. Molla G, Bitew M. Revolutionizing personalized medicine: synergy with multi-omics data generation, main hurdles, and future perspectives. Biomedicines 2024;12(12):2750.
7. Duruflé H, Selmani M, Ranocha P, Jamet E, Dunand C, Déjean S. A powerful framework for an integrative study with heterogeneous omics data: from univariate statistics to multi-block analysis. Brief Bioinform 2021;22(3):bbaa166.
8. Yetgin A. Revolutionizing multi‐omics analysis with artificial intelligence and data processing. Quant Biol 2025;13(3):e70002.
9. 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(10):695-713.
10. Nam AS, Chaligne R, Landau DA. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. Nat Rev Genet 2021;22(1):3-18.
11. Riess A, Roggia C, Selting AS, Lysenkov V, Ossowski S, Casadei N, et al. sc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome. Funct Integr Genomics 2025;25(1):101.
12. Du P, Fan R, Zhang N, Wu C, Zhang Y. Advances in integrated multi-omics analysis for drug-target identification. Biomolecules 2024;14(6):692.
13. Wu Y, Xie L. AI-driven multi-omics integration for multi-scale predictive modeling of genotype-environment-phenotype relationships. Comput Struct Biotechnol J 2025.
14. Cunha DR, Quinaz MB, Segundo MA. Biopharmaceutical analysis—current analytical challenges, limitations, and perspectives. ABC 2025:1-22.
15. Dhillon A, Singh A, Bhalla VK. A systematic review on biomarker identification for cancer diagnosis and prognosis in multi-omics: from computational needs to machine learning and deep learning. Arch Comput Method E 2023;30(2):917-949.
16. Zielinski JM, Luke JJ, Guglietta S, Krieg C. High throughput multi-omics approaches for clinical trial evaluation and drug discovery. Front Immunol 2021;12:590742.
17. Mohammadzadeh-Vardin T, Ghareyazi A, Gharizadeh A, Abbasi K, Rabiee HR. DeepDRA: Drug repurposing using multi-omics data integration with autoencoders. PLoS One 2024;19(7):e0307649.
18. Rozemberczki B, Gogleva A, Nilsson S, Edwards G, Nikolov A, Papa E. MOOMIN: deep molecular omics network for anti-cancer drug combination therapy. Proceedings of the 31st ACM international conference on information & knowledge management2022:3472-3483.
19. Tiew PY, Meldrum OW, Chotirmall SH. Applying next-generation sequencing and multi-omics in chronic obstructive pulmonary disease. Int J Mol Sci 2023;24(3):2955.
20. Zhao C, Dong J, Deng L, Tan Y, Jiang W, Cai Z. Molecular network strategy in multi-omics and mass spectrometry imaging. Curr Opin Chem Biol 2022;70:102199.
21. O'Connor LM, O'Connor BA, Lim SB, Zeng J, Lo CH. Integrative multi-omics and systems bioinformatics in translational neuroscience: A data mining perspective. J Pharm Anal 2023;13(8):836-850.
22. Koppad S, B A, Gkoutos GV, Acharjee A. Cloud computing enabled big multi-omics data analytics. Bioinform Biol Insights 2021;15:11779322211035921.
23. Mohr AE, Ortega-Santos CP, Whisner CM, Klein-Seetharaman J, Jasbi P. Navigating challenges and opportunities in multi-omics integration for personalized healthcare. Biomedicines 2024;12(7):1496.
24. Kaya HE, Naidoo KJ. CytoCopasi: a chemical systems biology target and drug discovery visual data analytics platform. Bioinformatics 2023;39(12):btad745.