Integrating Multi-Omics For A Holistic View of Biological Responses to Exercise

Integrating Multi-Omics For A Holistic View of Biological Responses to Exercise

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Over the past decade, “omics” has become increasingly popular. Omics refers to the field of biology that uses advanced technologies to study the roles, relationships, and actions of molecules within cells. Key areas include genomics (DNA study), proteomics (protein study), transcriptomics (RNA transcripts), metabolomics (small-molecule chemicals), epigenomics (epigenetic modifications), and lipidomics (lipids). In the omics approach, high-throughput technologies gather extensive quantities of data to better understand complex biological systems. Multi-omics integrates data from these areas, offering a holistic view of biological processes and leading to more precise medical treatments, improved disease diagnostics, and a better understanding of health and disease mechanisms.

Multi-omics have been gaining popularity, which usually integrates one or two platforms to map biological functions. In a recent investigation published in Nature,  the Molecular Transducers of Physical Activity Consortium (MoTrPAC) group used a comprehensive multi-omics approach with 25 platforms (including genomics, epigenomics, transcriptomics, metabolomics, and proteomics) on 19 tissues to create the first multi-omic whole-organism map of the temporal effects of endurance exercise training in male and female rats.

Endurance Training-Induced Gene Expression Remodelling Across Multiple Tissues

Using six extensively profiled tissues— gastrocnemius, heart, liver, white adipose tissue, lung, and kidney—the researchers identified ~ 11500 differential features mapped to ~7200  genes. Most training-responsive genes were tissue-specific, notably in white adipose tissue. Tissue-dependent adaptations were found in the regulation of immune cell recruitment and the transcriptome remodeling of lung tissue, as well as in the metabolic processes in gastrocnemius and liver cofactor synthesis. Unique responses at the transcript and protein levels were observed, with ~2400 genes differentially expressed in multiple tissues. A conserved immune-related pattern of expression was observed in the lungs and adipose tissue, while a mitochondrial metabolic signature was enriched in the heart and gastrocnemius. The insights into shared pathways offer potential therapeutic targets for individuals who are unable to exercise due to a variety of health issues

From Molecular Exercise Training Responses to Human Health Implications

Using an empirical Bayes graphical clustering approach, researchers analyzed 34,244 differential features over time to compare dynamic multi-omic responses to endurance training across tissues. This method summarizes molecular training responses and identifies feature groups that display similar patterns. Pathway enrichment analysis revealed several biological processes, such as chromatin accessibility regulation in the liver, lipid metabolism in the gastrocnemius, and blood protein translation and organelle biogenesis.

Through multi-tissue metabolic analyses of mitochondria and lipids, authors examined how endurance training affects organism-wide metabolic changes. They found that the liver showed the most significant metabolic changes, followed by the heart, lung, and hippocampus. Key findings included up-regulation of metabolites related to muscle protein turnover and cardiovascular disease, increased cortisol levels, and enhanced carbohydrate metabolism in the heart. Mitochondrial biogenesis increased in skeletal muscle, heart, and liver, with sex-specific changes observed. The liver showed significant regulation of metabolic pathways, enrichment in lipid-related metabolite classes, and protein acetylation changes, indicating improved liver health and protection against lipid storage and steatosis.

To improve translational validity, authors examined their findings against existing exercise studies and disease ontology annotations.

They found significant overlap between the transcriptome of  vastus lateralis and a meta-analysis of long-term training gene expression in human skeletal muscle. Adaptations in the gastrocnemius in humans were similar to those seen in high-intensity interval training. Down-regulated genes in white adipose tissue, kidney, and liver were associated with type 2 diabetes, cardiovascular disease, obesity, and kidney disease, highlighting their relevance to human studies.

Sex-Specific Responses to Endurance Training: Molecular Insights and Implications

In response to exercise, 58% of training-regulated features were sex-specific Notable differences included opposite responses in adrenal gland transcripts, lung phosphosites, and chromatin accessibility features, with distinct patterns in cytokine regulation between males and females. Male and female adrenal glands differentially underwent extensive transcriptional remodeling, especially in steroid hormone pathways. Lung phospho-signaling activity decreased primarily in males, with key proteins indicating sex-dependent changes in lung structure. Immune pathway enrichment analysis revealed down-regulation in the lung and small intestine but strong up-regulation in adipose tissue in males. These patterns suggest significant immune cell activity in male adipose tissue adaptation. In the small intestine, endurance training decreased inflammation-related transcripts and improved gut homeostasis, highlighting systemic anti-inflammatory effects.

These findings provide clearer insights into how males and females adapt differently to exercise, highlighting the importance of considering sex-specific responses in training and health interventions. The implication is that personalized exercise programs and treatments that account for these differences could be more effective, potentially improving health outcomes and performance.

This study is a great example of how multi-omics can enhance our understanding of complex biological interactions by integrating data from genomics, proteomics, metabolomics, and other omics fields. This approach can answer critical questions about the molecular mechanisms underlying health and disease, tissue-specific responses to interventions like exercise, and sex-specific differences in these responses. Ultimately, multi-omics holds the promise of leading to more personalized and effective medical treatments, thereby allowing for tailored therapeutic strategies that consider an individual’s unique molecular profile. By taking the multi-omic approach, we can move towards a future where medical interventions are not only more precise and granular but also significantly more effective, improving patient outcomes and overall health.

Outsourcing Bioinformatics Analysis: How Bridge Informatics (BI) Can Help

We are passionate about empowering life science companies with cutting-edge technologies. BI data scientists are experts in omics and the integration of multi-omics, prioritizing the study, understanding, and reporting of the latest developments so we can advise our clients confidently. Our bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis.

From pipeline development and software engineering to deploying your existing bioinformatic tools, BI can help you on every step of your research journey. As experts across data types from leading sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing and interpreting genomic and transcriptomic data. Click here to schedule a free introductory call with a member of our team.

Shahrzad Ghazisaeidi, PhD, Data Scientist, Bridge Informatics

Shahrzad specializes in high-throughput sequencing, data pre-processing, and downstream analysis of transcriptomic and epigenetic landscapes. She is particularly passionate about developing innovative tools for drug repurposing.

Prior to joining Bridge Informatics, Shahrzad served as a Postdoctoral Associate at the Hospital for Sick Children in Toronto, Canada where she researched the epigenetics of peripheral nerve injury models.

Shahrzad earned her Ph.D. in Physiology and Neuroscience from the University of Toronto. Her studies focused on the sex-dependent and independent gene regulation of peripheral nerve injury. Currently based in Toronto, Shahrzad balances her professional pursuits with personal interests by making time for yoga, martial arts, and poetry.

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