A paper published today in Nature describes the first human interactome reference map, constituting a "scaffold" of information to better understand how faulty genes cause diseases such as cancer, but also how viruses such as SARS-CoV-2 interact with their host human proteins.
"Since the mid-1990s, our collaborative team has pushed the idea that interactome maps can illuminate fundamental aspects of life," says senior author Marc Vidal from Dana-Farber Cancer Institute. Almost a decade in the making, the human protein map is now available thanks to a joint effort, involving over 80 researchers in the United States, Canada, Spain, Belgium, France and Israel.
The Human Reference Interactome (HuRI) map charts 52,569 interactions between 8,275 human proteins.
Humans have about 20,000 protein-coding genes but scientists still know remarkably little about most of the proteins they encode. Fortunately, this information can be gleaned from interaction data thanks to the "guilt by association" principle, according to which two proteins that have similar interacting partners are likely involved in similar biological processes.
The data are already revealing important insights such as new cellular roles for human proteins and what goes wrong at the molecular level to spur on disease. In this vein, HuRI has already revealed new functions for proteins involved in programmed cell death, release of cellular cargo and other processes. And, by integrating protein interaction data with tissue-specific gene expression, the teams have been able to identify protein networks behind the development and maintenance of different tissues, revealing new therapeutic targets for diverse genetic diseases including cancer and potentially for infectious diseases as well.
Although it is the largest map of its kind to date, the map remains incomplete, representing between 2-11 per cent of all human protein interactions. According to the researchers, one reason why many interactions were missed is probably because yeast cells lack certain human-specific molecular factors that are needed for proper protein function.
Image: By charting pairwise interactions between 17,500 human proteins, scientists have created a map, on the left, depicting which proteins work together to sustain cellular function. Proteins with similar interactions profiles fall into discrete colour-coded clusters representing different bioprocesses in the cell. Image courtesy of Katja Luck et al.