A new molecular map of human populations paves the way for precision medicine

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The study—co-led by Manuel Fuentes, a researcher at the Cancer Research Center (CSIC, USAL, FICUS) and IBSAL, and Pablo Juanes Velasco, technical director of the IBSAL Proteomics Platform—analyzes data from hundreds of healthy individuals from different countries and backgrounds. Its goal is to understand how factors such as genetics, geography, and diet influence the state of the immune system, overall health, and the aging process.

To this end, the team has integrated more than ten “omic” layers, that is, large sets of biological data such as genomics (genes), proteomics (proteins), metabolomics (metabolites), and the microbiome (microorganisms in the body), which provide a comprehensive view of how the human body functions.

Differences in the way people age, even when they are the same age, and the fact that certain lifestyle habits or diets are more effective in some populations than in others are among the issues addressed by a comprehensive international study, which has produced one of the most complete molecular maps to date of healthy people of different ancestries, ages, and places of residence. ​

The research findings have been published in the journal *Cell* under the title“A Comparison of Deep Multiomics Profiles Across Ethnicity, Geography, and Age.” The research is part of the Human Personal Omics Profiling (hPOP) project, led and coordinated by Stanford University.

Over the course of several years, the research team has collected blood, urine, and stool samples from 322 healthy individuals in various countries on different continents, including Taiwan, Ireland, the United States, and Canada. The data have been supplemented with other information, such as clinical data, lifestyle, diet, and place of residence. Based on these samples, a molecular analysis was conducted that incorporated data from genomics, transcriptomics, proteomics, metabolomics, lipidomics, metallomics, glycomics, metabolic hormone analysis, antibodies against pathogens, and a comprehensive characterization of the gut microbiome using various high-throughput technologies.

“This study allows us to observe, layer by layer, how different biological systems—including the immune system— are organized and interact in apparently healthy individuals, and how genetic background and the environment modulate those systems, explains Manuel Fuentes, a researcher at the Cancer Research Center and IBSAL and a professor at the University of Salamanca, who is among the lead authors of the study.

Pablo Juanes, technical director of the IBSAL Proteomics Platform and one of the lead authors, comments, “From a proteomics perspective, we have been able to provide very valuable information on the dynamics of the immune response in healthy individuals of different ages, under various climatic conditions, and with different lifestyles… demonstrating the enormous potential of proteomics for immune monitoring in any physiological situation.”

“This study allows us to determine the immunological fingerprint—how it is influenced by the environment and surroundings (climate, season…), diet, microbiota, infections, vaccinations, lifestyle, stress, hormonal changes, and genetics, along with social and geographic factors,” says Manuel Fuentes.

“In this regard—in determining the state of the immune system and its response— this is the first map that allows us to establish, as a reference, the immune signature or status of each individual, paving the way for future studies on susceptibility to infections, autoimmunity, and so on,” notes Pablo Juanes.

Ethnicity, Environment, and Aging Clocks

One of the study’s key findings is that genetic ancestry (referred to as “ethnicity” in the article) is associated with very distinct profiles in the immune system, metabolism, certain drug targets, susceptibility to autoimmune diseases, and the composition of the microbiome. At the same time, geography—that is, where each person lives— and moves to a different country or continent reshape these molecular and microbial networks, even affecting the so-called “biological clocks” of aging.

​The study analyzes what is known as biological age —a measure of the body’s actual “wear and tear” calculated from multiple molecular data points—and compares it to chronological age, which is simply the number of years lived.

The research team calculated biological age markers based on various omics data and observed that not all populations age at the same rate, even if they are the same chronological age. For example, people of East Asian descent have a lower biological age when they live in their ancestral regions, while those of European descent have a lower biological age when living in the United States or Canada than when they lived in Europe, suggesting that environment and lifestyle play a very significant role.

Diet, the Microbiome, and Personalized Health

The study also delves into how diet interacts with the gut microbiome in ways that are specific to genetic ancestry. It has been shown to modulate key metabolic pathways linked to health, such as lipid metabolism, bile acid metabolism, and the arachidonic acid pathway. The interactions between diet, the microbiome, and genetics help explain why certain dietary patterns or environments are beneficial for some populations but not as much for others, and they provide a scientific basis for designing nutritional guidelines and prevention strategies that are better tailored to each group.

“The data show that there is no single solution that works for everyone; precision medicine must take into account both genetic information and the immunological signature, along with each individual’s geographic, environmental, and cultural context,” emphasizes Manuel Fuentes.

An open resource for the scientific community

The study has generated a fully open-access data resource that will enable other research groups to explore a wide range of questions about how genetics and the environment interact to influence health, disease risk, and response to treatments. The team has validated its findings in several independent cohorts and has integrated large volumes of omics, clinical, and environmental data.

“For the Cancer Research Center, participating in a multi-omic study of this caliber reinforces our role at the international forefront of biomedicine and personalized medicine,” Fuentes notes. “The CIC’s expertise in immune monitoring, combined with the role of the IBSAL Proteomics Platform in characterizing complex proteomic profiles, is key to understanding how these molecular networks can help us prevent diseases and personalize treatments in the future.”

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