Interactive Human Protein Atlas Launches

Researchers in Sweden have completed a major analysis of the human proteome and presented their results in a free, interactive web portal that allows researchers to visualize the distribution of proteins across all of the body's major tissues and organs, potentially accelerating cancer research and drug development.

The tissue-based map of the human proteome, described in an article published in Science, contains RNA and protein expression profiles covering more than 90% of the putative protein-encoding genes in 32 tissues and organs of the body, accompanied by more than 13 million high-resolution images (Science 2015;347:1260419). The data is presented via the Human Protein Atlas web portal, where researchers can conduct advanced searches, download information, and cross-reference with other major biologic resources (see www.proteinatlas.org).

“To visualize the localization of where a protein is expressed in the context of the normal tissue in which these cells reside provides basic knowledge connecting gene/protein expression and cellular phenotype,” says senior author Fredrik Pontén, MD, PhD, professor of pathology at Uppsala University in Sweden. “Visualization allows for information regarding subpopulations of cells and whether expressed proteins are associated to certain phenomena, such as differentiation and proliferation.”

The analysis differs from previous efforts to map the human proteome in that it uses immunohistochemistry, as opposed to mass spectrometry, to analyze protein levels in tissues, says Pontén. Mass spectrometry quantifies mean protein levels in whole samples of tissue, whereas antibody-based protein detection using immunohistochemistry and immunofluorescence provides resolution at the cellular and subcellular levels.

“A major difference is the spatial resolution,” he explains. “Combining RNA sequencing to get quantitative measures of mRNA in the different tissue types with immunohistochemistry to get spatial information on where the corresponding proteins are expressed provides a map of where and how different categories of proteins—such as tissue-enriched proteins, housekeeping proteins, transcription factors, and membrane-bound proteins—are expressed.”

The main atlas is divided into four sub-atlases—tissue, cell line, subcellular, and cancer—and contains detailed analyses of proteomes related to certain features, such as the druggable proteome, including all proteins targeted by existing drugs, and the cancer proteome, encompassing protein expression data for genes implicated in cancer. Researchers provided immunohistochemistry-based protein expression profiles for more than 200 individual cancers corresponding to the 20 most common forms of human cancer.

“This means that for every gene, the corresponding protein expression pattern in different cancer types can be assessed,” says Pontén. “Researchers interested in various genes or cancers can go into the atlas and see how a given protein is expressed across a specific type of cancer.”

The new analysis reveals that almost half of protein-encoding genes implicated in cancer are expressed across all tissues while only a small percentage of our genes are tissue-specific.

“Tissue specificity versus widespread expression patterns can help identify diagnostic markers and develop drugs targeting specific cancer types,” says Pontén. “The definition of proteins expressed in all tissue types has bearing on drug targets, since 30% of all FDA-approved drug targets are expressed in all tissues.”

For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.