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Advancing the Atlas
STOCKHOLM—The Human Genome Project was a massive, international undertaking to sequence the entirety of the human genome, and one that revolutionized the collective understanding of human genetics. The scope of the work—and the data it generated—led to countless discoveries, and has inspired similar mapping efforts since then.
In a similar vein, the latest database released by the Swedish-based Human Protein Atlas program is the Blood Atlas, which provides a directory of human immune cells and their respective proteins. Led by Mathias Uhlén, professor at the Department of Protein Science at KTH Royal Institute of Technology and visiting professor at the Department of Neuroscience at Karolinska Institutet, the open-access database provides a wealth of information about the immune system and the genes and proteins associated with immune cells.
The research for this work took place primarily at the Science for Life Laboratory (SciLifeLab), a joint research center between KTH, Karolinska Institutet, Stockholm University and Uppsala University. Participants included SciLifeLab (with researchers from KTH, Karolinska Institutet and Uppsala University) and Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark. Major funding came from the Knut and Alice Wallenberg Foundation, and the results were published in Science in a paper titled “A genome-wide transcriptomic analysis of protein-coding genes in human blood cells.”
“The immune cells are involved in fighting all human diseases—in particular, cancer, infectious diseases and autoimmune diseases,” Uhlén commented in a KTH press release. “With a comprehensive map identifying all proteins in these blood cells, researchers around the world will be able to deepen their understanding of human biology and develop new, more effective therapies targeting these diseases.”
According to the paper, the researchers' approach consisted of the following: “A quantitative transcriptomics-based expression analysis was performed in 18 canonical immune cell populations isolated by flow cytometric sorting. The blood cell expression profiles are presented in combination with expression profiles of tissues, including transcriptomics data from external sources to expand the number of tissue types as well as brain regions included in the database. A genome-wide classification of the protein-coding genes has been performed in terms of expression specificity and distribution, both in blood cells and tissues.”
“A genome-wide analysis of blood cell RNA expression profiles allowed the identification of genes with elevated expression in various immune cells, confirming well-known protein markers, but also identified novel targets for in-depth analysis. There are 1,448 protein-coding genes that have enriched expression in a single immune cell type,” the authors added.
“This resource is very important for anyone interested in understanding the function of individual genes, for example in patents with primary immune deficiency diseases,” stated Petter Brodin, pediatrician and associate professor at the Department of Women’s and Children’s Health at Karolinska Institutet and last author of the paper.
Of the cell types categorized in this work, the authors noted that “many of the cell type-enriched genes are in neutrophils, eosinophils and plasmacytoid dendritic cells, while many of the elevated genes in T and B cells are group-enriched across subpopulations of these lymphocytes.” The paper also highlighted genes known to play a role in common immunodeficiencies, many of which “are expressed in cells not currently implicated in these diseases.”
In addition to the results of this latest work, the Blood Atlas also includes information on the team's work with the “secretome.”
“The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnostics and therapy. Based on a genome-wide analysis of the human protein-coding genes in which the secretome was identified as proteins with a signal peptide and no transmembrane-spanning region, altogether 2,641 genes were identified, corresponding to approximately 13 percent of the protein-coding genes,” as reported on the Human Protein Atlas website. “We have here performed a systematic analysis of all of these genes in order to identify through literature, bioinfomatics and experimental data the final location of each of these predicted secreted proteins, with the aim to annotate their final location in the human body, including blood, digestive tract or other locations. A large portion of the proteins were annotated as intracellular, including locations in the Golgi, ER and other intracellular compartments.”
In support of the importance of the Blood Atlas, of those 2,641 genes, 729 are ones with proteins secreted to the blood—the highest amount next to the category of intracellular and membrane proteins (933).
The results of the Blood Atlas research can be found on the Human Protein Atlas website at https://www.proteinatlas.org/humanproteome/blood.