Human ‘molecular map’ contributes to understanding disease mechanisms

Scientists at Weill Cornell Medicine in Qatar (WCM-Q) have created a detailed molecular map of the human body and its complex physiological processes based on the analysis of thousands of molecules in blood, urine and saliva samples from 391 volunteers. The data has been integrated to create a powerful, interactive online visual tool called Connecting Omics (COmics) that can be used to study the complex molecular makeup of humans and uncover underlying traits associated with various diseases.

Molecular processes in the human body refer to the chemical reactions and interactions occurring within and between cells, including crucial functions such as DNA replication, protein synthesis, energy production, cellular communication, and various metabolic pathways, all of which are governed by complex protein-protein, protein-DNA, and protein-RNA interactions, thereby enabling vital body functions.

The comprehensive study, published on August 19 in Nature Communicationsgathered 12 years of data from the Qatar Diabetes Metabolomics Study (QMDiab), a case-control study of diabetes among Qatar’s multi-ethnic population, primarily of Arab, Filipino, and Indian origin.

“Our idea was to bring together everything we have learned over more than a decade of multiomics research to create a comprehensive molecular model of the human body and its processes,” said Dr. Karsten Suhre, senior author of the study, professor of physiology and biophysics and member of the Englander Institute of Precision Medicine. “This reference tool is freely available and usable by researchers who want to study how the human body works at the molecular level and also for formulating hypotheses to test through experimentation.”

Through a collaboration with Hamad Medical Corporation, the researchers collected multiple aliquots of blood, urine, and saliva samples from volunteers with and without diabetes. The samples were then characterized on 18 different high-throughput analysis platforms, providing an extremely rich dataset comprising 6,300 individual molecular data points, including genomic (DNA), transcriptome (RNA), proteins, and metabolites, such as amino acids, sugars, and fats. In addition, they determined information on genetic variants, DNA methylation sites, and gene expression for each of the participants.

The researchers were able to discover associations and pathways linking genetic characteristics to specific proteins, metabolic processes and diseases. They then carefully integrated the mass of data from all individuals into an online tool that serves as an interface to “The Molecular Human”, the molecular description of the human body.

The approach that combines genomics, transcriptomics, metabolomics, proteomics, and other forms of so-called “omics” research is known as multiomics. This approach has emerged in recent years as a key strategy for biomedical researchers seeking to understand how the human body and diseases actually work, providing information that could potentially enable the development of new drug therapies.

For example, the study identified and described proteins and metabolites that are signatures of type 2 diabetes subtypes, shedding light on the different ways the disease manifests.

“Our integrative omics approach provides insight into the interrelationships between different molecular traits and their association with a person’s phenotype – their observable traits, such as physical appearance, biochemical processes and behaviors,” said first author Dr. Anna Halama, assistant research professor of physiology and biophysics.

“The breadth of data integrated into the COmics web tool gives researchers access to hundreds of thousands of pathways and associations to explore, offering enormous potential for discovery and investigation.”