The protein EGFR (epidermal growth factor receptor) is visualized using confocal microscopy and immunofluorescent reporters in a human cell line (A-431). EGFR is localized to the plasma membrane (green). The cytoskeleton and microtubules are shown in red and the nucleus in blue. Photo: Chalmers University of Technology

First analysis of Human Protein Atlas

Biotechnology and biochemistry
A better comprehension of proteins involved in diseases such as cancer and diabetes. These are some of the benefits of the first analysis of the Human Protein Atlas – a major research project for mapping all the human proteins.

Chalmers University of Technology and DTU Biosustain recently became involved in the KTH, Royal Institute of Technology, driven research project on generating a tissue-based map of the human proteome called the Human Protein Atlas. Now the universities have contributed with advanced analysis of human metabolism.

Results of the analysis, published as a research article in Science, presents a major analysis of 32 tissues and represents a significant advancement of the Human Protein Atlas. The article includes a detailed picture of the proteins that are linked to cancer, the number of proteins present in the bloodstream, and the targets for all approved drugs on the market. Work at the universities have enabled a new insight into how metabolism differs in 32 different tissues, which may pave the way for new drug treatment strategies.

“It has been very exciting to engage in the Human Protein Atlas project, the largest research project in Sweden. We could hereby demonstrate how we could use their proteome data to generate detailed metabolic models for different human tissues. We expect this will have a significant impact on our understanding of human metabolic diseases like obesity, diabetes and cancer “, says Jens Nielsen, Scientific Director DTU BIOSUSTAIN, Novo Nordisk Foundation Center for Biosustainability and Professor at the Department of Biology and Biological Engineering, Chalmers.

A major multinational research project
The Human Protein Atlas, a major multinational research project supported by the Knut and Alice Wallenberg Foundation, recently launched (November 6, 2014) an open source tissue-based interactive map of the human proteome. Based on 13 million annotated images, the database maps the distribution of proteins in all major tissues and organs in the human body, showing both proteins restricted to certain tissues, such as the brain, heart, or liver, and those present in all. As an open access resource, it is expected to help drive the development of new diagnostics and drugs, but also to provide basic insights in normal human biology.

“In the Science article, Tissue-based Atlas of the Human Proteome, the approximately 20,000 protein coding genes in humans have been analysed and classified using a combination of genomics, transcriptomics, proteomics, and antibody-based profiling”, says the article's lead author, Mathias Uhlén, Scientific Director DTU BIOSUSTAIN, Novo Nordisk Foundation Center for Biosustainability and Professor of Microbiology at Stockholm's KTH Royal Institute of Technology and the director of the Human Protein Atlas program.

Expressed in a ubiquitous manner
The analysis shows that almost half of the protein-coding genes are expressed in a ubiquitous manner and thus found in all analysed tissues. Approximately 15 percent of the genes show an enriched expression in one or several tissues or organs, including well-known tissue-specific proteins, such as insulin and troponin. The testes, or testicles, have the most tissue-enriched proteins followed by the brain and the liver.

The analysis suggests that approximately 3,000 proteins are secreted from the cells and an additional 5,500 proteins are located to the membrane systems of the cells. The analysis also contains a study of the metabolic reactions occurring in different parts of the human body. The most specialised organ is the liver with a large number of chemical reactions not found in other parts of the human body.

The study has been carried out by researchers in Sweden at Chalmers University of Technology/ Technical University of Denmark, KTH - Royal Institute of Technology, Uppsala University, Karolinska Institute, Lund University, and Stockholm University.