For the first time, gene expression has been studied in 46 tissues and organs of hundreds of people with different traits, such as age, sex, genetic ancestry or weight.
The research provides fundamental information on how the activation of these genes changes with age, between men and women or between individuals of different geographical origins, allowing a significant advance towards personalized medicine.
The study also tests how diabetes affects nerve tissue and identifies for the first time in humans the specific genes that change in the nerves of diabetic people.
This work reinforces the BSC's position as one of the world's leading centers in biomedical data analysis.
Researchers at the Barcelona Supercomputing Center - Centro Nacional de Supercomputación (BSC-CNS) have led a study, published in the journal Cell Genomics, which for the first time analyzes the variation in the expression of our genes in organs and tissues of the human body in hundreds of individuals with different traits. The work helps us to understand how the behavior of our genes differentiates us from others and provides fundamental information for deciphering human biology and the functioning of diseases such as diabetes.
The main novelty of the study is that all the genes of the genome have been analyzed at the same time in multiple human tissues considering several demographic and clinical traits, something that had not been done before. The results reveal specific differences in the expression of these genes in healthy people according to age, sex, genetic ancestry (the geographic origin of their genome) and body mass index (BMI), which allows us to assess a possible risk and progression of certain diseases.
Research, therefore, allows us to learn more about what makes us unique and how gene behavior changes between people with different characteristics. This is important, for example, in understanding why some diseases manifest themselves differently in women and men or with age, paving the way for precision medicine tailored to the traits of each patient.
Analysis of the 20,000 genes in the genome of 781 people
The genetic information we have in all the cells of the body is the same. What makes each cell act or be different in tissues or organs is the differential activation of genes, known as gene expression. The BSC study has analyzed the more than 20,000 genes of the human genome in 46 tissues of 781 individuals participating in the GTEx project (The Genotype-Tissue Expression Project), to determine how this gene expression varies according to the traits of each person.
"The question we were trying to answer is: which of these characteristics -sex, age, ancestry, weight or disease- affects gene expression the most? What we have seen is that it varies a lot between different tissues. For example, with age, the tissues that change the most are the arteries. Between men and women, the tissues that vary the most are the thyroid and breast tissue, while the most important differences depending on genetic ancestry have been found in the skin," says Marta Melé, leader of the Transcriptomics and Functional Genomics group of the BSC's Life Sciences Department.
"In some tissues, such as breast tissue, we found an interaction between two traits - age and sex - indicating that breast tissue aging is different between men and women. The relevance of the study is that not only have we detected these differences, but we have also identified the specific genes that explain this variation," adds Melé.
Diabetes especially affects nervous tissue
The study has also analyzed how gene expression changes with diabetes, a disease that affects 200 million people and is a major public health problem worldwide. The results show that diabetes particularly affects nerve tissue through a condition known as diabetic neuropathy, which one in two diabetics will eventually develop at some point in their lives.
"We have found that the effect of diabetes on nerves is similar to that of aging. Diabetes ages the nerves because it affects the same genes as age, so that the nerve tissue of a young diabetic person resembles that of an older person," highlights Raquel García, first author of the study and member of the BSC's Transcriptomics and Functional Genomics group. "Not only do we see that the nerve tissue is affected, but we can also identify the genes that change specifically in the nerves of diabetic patients, something that had not been possible until now in humans," she adds.
The identification of these genes, involved in nerve impulse and communication between neurons, allows a better understanding of the mechanisms involved in diabetic neuropathy, which could contribute to the development of new treatments for a disease that to date has no cure.
The BSC, a world leader in biomedical data analysis
One of the main challenges of the study has been the computational analysis of the huge amount of massive data from the GTEx consortium, something that has only been possible thanks to the high computational capacity of the BSC's MareNostrum 4 supercomputer. "Just to store the data from this project, we would need 750 laptops like the ones we have at home," says José Miguel Ramirez, co-author of the article and member of the BSC's Transcriptomics and Functional Genomics group.
This research once again highlights the importance of high-performance computing in genomic research and positions the BSC as one of the most important centers worldwide in the analysis of biomedical data.
In short, the study represents a significant advance in the knowledge of our genes, which opens the door to the development of personalized medicine with a high level of precision. If we know which genes make each person unique and different, the diagnosis of certain diseases could be done earlier and the treatments would be more adapted to each patient according to his or her traits and the behavior of these genes.
- Reference: Raquel García-Pérez, Jose Miguel Ramirez, Aida Ripoll-Cladellas, et al. The landscape of expression and alternative splicing variation across human traits, Cell Genomics, 2022, 100244, ISSN 2666-979X, https://doi.org/10.1016/j.xgen.2022.100244.
- Caption: BSC researcher Marta Melé and Jose Miguel Ramírez, authors of the study.