Proteome

Scientists from EMBL Heidelberg have discovered that the collection of proteins in an animal cell; called the proteome is substantially affecting both the animal’s sex and its diet. Understanding these individual proteomes might provide a basis for personalized treatments for humans in the future.

“The goal of the study was to understand whether different proteins; within the proteome interact with each other the same way in different individuals and; if not, what factors cause the differences,” explains first author Natalie Romanov; postdoctoral researcher in Peer Bork’s group at EMBL Heidelberg. The study of the individual proteomes the proteotypes delivered a surprising result. It showed that a significant part around 12% of the proteotype variation is determining by both sex and diet; this is more than expected.
So far, only a few proteins were knowing to be up- or down-regulating; according to the genetic sex of an animal or its diet. Sex-specific differences, for example; are usually tracing back to chromosome X/Y-specific gene expression; but the new study showing that a lot more proteins are affecting. The impact of diet was restricting to a smaller complementary set of protein machineries. “It’s impressive that these two factors alone already account; for a large part of an individual’s proteotype,” says Romanov.

Proteotype-directed personalized medicine

The future of medical treatment lies in personalized medicine; in which products are tailoring to individual patients. So far, most studies have focused on adapting treatments to the genotype; the genetic makeup of a cell encoded in the DNA. However, while some rare diseases are clearly genetically determine; for most diseases the environment plays a major role and the genome of the patient only has a minor contribution.

“In the case of obesity, for example, only about 6% of the variation; in the body mass index can be explaining the associated genetics,” says Peer Bork. “The proteotype reflects not only the genetics but also environmental aspects, for example the lifestyle. As such, understanding proteotypes holds great promise for providing life-style-associated fingerprints in individuals.”

This study provides a major stepping stone in understanding which cellular alterations; in a disease individual are potentially reversing changing life-style. This knowledge could not only be useful for disease diagnosis but also to individualize therapies in the future.

A first small step

The team obtained their results by analysing 11 large public data-sets; containing detailed information on different proteotypes in humans and mice; as well as their diet and genetic status. It is only with recent advances in the throughput of mass spectroscopy; that such large databases on individual proteotypes was possible. Despite technological advancements the creation of these databases is still expensive.
“The results provide a first step only. It can be assumed that many other parameters besides sex; and diet need to be fully tested to potentially reshape the proteotype of an individual; from a diseased to a healthier state,” concludes Martin Beck, one of the co-authors. “To understand most of the differences in proteotypes of individuals many more such data-sets need to be collected. We also need to test for many more environmental and genetic factors before respective diagnostics and individualized therapies can be pushed into the clinics.”