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When the human spermatozoid helps to decipher the human proteome

Researchers at the Large Scale Biology laboratory are very active in the Human Proteome Project. Thus, the strategy for mass analysis of proteomic data that they proposed [collaboration] allowed them to identify in the proteome of human sperm more than 5000 proteins of which 220 never previously reported.

Published on 20 February 2018
The Human Proteome Project (HPP) is an international project launched by HUPO (Human Proteome Organization) and involving 50 teams over 25 countries. The absence of experimental data on proteins encoded by approximately 30% of predicted human genes requires a systematic effort to confirm the existence of these proteins, determine their abundance, distribution, subcellular localization, and so on. This effort is carried out as part of an international program, the HPP program. The benefits of the HPP project should enrich the understanding of human biology and lay the foundation for the development of diagnostic, prognostic, therapeutic and preventive medical applications.

The first phase of the HPP program aimed to map the proteins encoded by the human genome by identifying at least one representative protein for each of the approximately 20,300 human protein-coding genes. Proteins predicted by genomic or transcriptomic analysis but not yet validated experimentally by mass-spectrometry (MS) and/or antibody-based techniques are called missing proteins (MPs).
In 2013, France* joined forces with Switzerland*; this contribution resulted in the design of a bioinformatic strategy for mass analysis of proteomic data (from 40 human samples analyzed by mass spectrometry) [1]. In the context of the announcement of the completion of the human proteome for which methodological biases were noted, the strategy proposed by the Franco-Swiss contribution made it possible to propose mass spectrometry validation criteria as part of guidelines for the certification of MPs by the HPP consortium [2].
In 2016, the Franco-Swiss consortium focused its efforts on an in-depth analysis of the proteome of human semen, a germ line potentially enriched in MPs based on our knowledge of transcriptomic profiles. The combined use of fractionation techniques, mass spectrometry analysis and bioinformatics, followed by validation using targeted mass spectrometry and immuno-histochemistry, identified more than 5000 proteins in the spermatozoid, of which 220 MPs never previously reported [3-5]. All these works earned the "HPP Investigator Award" to Yves Vandenbrouck (Exploring the Dynamics of Proteomes team, Large Scale Biology laboratory), pilot project for the ProFI infrastructure.
In addition to contributing to the HPP project, these results should also benefit the community of reproductive biology, particularly in the search for candidate markers of human idiopathic infertility, an important societal issue.

Among the organizations involved in the Human Proteome Project (HPP):
* France, represented by the ProFI infrastructure (Proteomics French Infrastructure)
* Switzerland is developing the reference base of the human proteome "neXtProt" (Swiss Institute of Bioinformatics)

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