Swedish scientists show the impact of approved drugs on human proteins
A research article published in Science presents the first major analysis based on the Human Protein Atlas, including a detailed picture of the proteins that are linked to cancer, and the targets for all approved drugs on the market.
The Human Protein Atlas, launched in November 2014, is 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. 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 newly published Science article, over 90 percent of the approximately 20,000 protein coding genes in humans were analysed. The study shows that some proteins are present in all tissues and others in specific organs such as heart, liver and blood. This information is important for the pharmaceutical industry. The 618 proteins that act as targets of all approved drugs on the market were analysed specifically, and it was shown that 70 percent of these were excreted or in the cell membrane.
Present in all tissues
The information can be used to explain how different drugs work and why some of them have side effects. For example, the analysis showed that 30 percent of the targets are present in all tissues. This can explain why certain drugs have side effects. The researchers hope that the results of the analysis can be used to develop improved drugs in the future.
“It is such a great time to do research", said study co-author Jan Mulder, researcher at the Department of Neuroscience at Karolinska Institutet and affiliated to the national research facility Science for Life Laboratory (SciLifeLab). "By completing the human protein atlas we are now able to retrospectively look at drug targets and their distribution in normal tissue. The next step would be to utilize this data and other global expression data that is rapidly being generated to find new and better targets for many of the diseases humanity struggles with.”
This study was carried out by researchers in Sweden at Royal Institute of Technology (KTH), Uppsala University, Karolinska Institutet, Chalmers University of Technology, Lund University, Stockholm University, and SciLifeLab. It was funded by the Knut and Alice Wallenberg Foundation. The research was led by Mattias Uhlén at KTH and SciLifeLab.
Tissue-based map of the human proteome
Mathias Uhlén, Linn Fagerberg, Björn M Hallström, Cecilia Lindskog, Per Oksvold, Adil Mardinoglu, Åsa Sivertsson, Caroline Kampf, Evelina Sjöstedt, Anna Asplund, IngMarie Olsson, Karolina Edlund, Emma Lundberg, Sanjay Navani, Cristina Al-Khalili Szigyarto, Jacob Odeberg, Dijana Djureinovic, Jenny Ottosson Takanen, Sophia Hober, Tove Alm, Per-Henrik Edqvist, Holger Berling, Hanna Tegel, Jan Mulder, Johan Rockberg, Peter Nilsson, Jochen M Schwenk, Marica Hamsten, Kalle von Feilitzen, Mattias Forsberg, Lukas Persson, Fredric Johansson, Martin Zwahlen, Gunnar von Heijne, Jens Nielsen, Fredrik Pontén
Science, online 23 January 2015, doi: 10.1126/science.1260419