News

doi:10.1038/nindia.2015.11 Published online 23 January 2015

Mapping proteins in human tissues

Richa Malhotra

An international consortium of researchers has created a catalogue of proteins that build the human tissues and organs, pinpointing which proteins are present where and at what levels1. The catalogue will help in new drug development.

Part of the Human Protein Atlas project launched in 2003, the catalogue also pictures proteins in individual cells and generates an open source database of 13 million images.

The epidermal growth factor receptor (EGFR) protein visualised using confocal microscopy and immunofluorescent reporters in a human cell line (A-431)
© The Human Protein Atlas
To profile proteins the researchers examined 44 human tissue and organ samples using a technique that exploits antigen–antibody interaction. The antigen here is a protein in the sample and antibody a reagent that binds to the protein. 

Since antibody reagents were available only for a handful of proteins, the team had to make scores of reagents in-house to be able to spot every protein. There are 20,000 odd protein-coding genes, some of which code for more than one. In all, they deployed 24,028 reagents corresponding to proteins coded by almost 17,000 genes.

The mRNA translates the genetic code (DNA) into proteins. So the researchers matched the expression patterns of proteins with those of mRNA in 32 tissue types. According to Sanjay Navani, Director of the India site for Human Protein Atlas at Lab Surgpath, Mumbai, this validates that the antibodies synthesised and data obtained subsequently are reliable.

Navani and colleagues found that 44% of protein-coding genes make proteins in all tissues. These omnipresent genes include the housekeeping ones responsible for functions essential to a cell, like metabolism, growth, energy production and division.

Acrosomal vesicle protein 1, expressed in testis, associated with acrosomal membranes in the head of a sperm
© The Human Protein Atlas
Alongside housekeeping proteins, their research spanned secreted, membrane-bound and regulatory proteins as well as proteins that are pharmaceutical drug targets or are involved in cancer progression.

About 30% of the FDA-approved drugs were found to aim at proteins expressed in all tissues and organs, with possible ramifications for cures targeting these proteins, the researchers caution.

Looking at protein expression in 36 cancer-derived cell lines, they found that several genes that make high levels of proteins in a tissue are partly or fully suppressed in a cell line, while housekeeping genes (involved in cell division) maintain similar levels of proteins in both. This suggests that results from cell line model systems should be carefully extrapolated to the corresponding human tissues.  

But the research is not the only one to map human proteome. Professor at Technische Universitaet Muenchen in Germany, Bernhard Küster, who led one of the two independent groups that simultaneously published proteome maps last year2,3 told Nature India that it addresses the same overall question “by an entirely different experimental technique [using antibodies], which has always served science well in the past.”


References

1. Uhlén, M. et al. Tissue-based map of the human proteome. Science (2015) doi: 10.1126/science.1260419
2. Kim, M. S. et al. A draft map of the human proteome. Nature (2014) doi: 10.1038/nature13302
3. Wilhelm, M. et al. Mass-spectrometry-based draft of the human proteome. Nature (2014) doi: 10.1038/nature13319