Lydie Lane

Crumbs is an apical transmembrane protein crucial for epithelial morphogenesis in Drosophila melanogaster embryos. A protein with all the characteristics for a Crumbs homologue has been identified from patients suffering from retinitis pigmentosa group 12, but this protein (CRB1) is only expressed in retina and some parts of the brain, both in human and mouse. Here, we describe CRB3, another Crumbs homologue that is preferentially expressed in epithelial tissues and skeletal muscles in human. CRB3 shares the conserved cytoplasmic domain with other Crumbs but exhibits a very short extracellular domain without the EGF- and laminin A-like G repeats present in the other Crumbs. CRB3 is localized to the apical and subapical area of epithelial cells from the mouse and human intestine, suggesting that it could play a role in epithelial morphogenesis. Indeed, expression of CRB3 or of a chimera containing the extracellular domain of the neurotrophin receptor p75NTR and the transmembrane and cytoplasmic domains of CRB3 led to a slower development of functional tight junctions in Madin-Darby canine kidney cells. This phenotype relied on the presence of CRB3 four last amino acids (ERLI) that are involved in a direct interaction with Par6, a regulator of epithelial polarity and tight junction formation. Thus, CRB3, through its cytoplasmic domain and its interactors, plays a role in apical membrane morphogenesis and tight junction regulation.

The neXtProt knowledgebase (https://www.nextprot.org) is an integrative resource providing both data on human protein and the tools to explore these. In order to provide comprehensive and up-to-date data, we evaluate and add new data sets. We describe the incorporation of three new data sets that provide expression, function, protein-protein binary interaction, post-translational modifications (PTM) and variant information. New SPARQL query examples illustrating uses of the new data were added. neXtProt has continued to develop tools for proteomics. We have improved the peptide uniqueness checker and have implemented a new protein digestion tool. Together, these tools make it possible to determine which proteases can be used to identify trypsin-resistant proteins by mass spectrometry. In terms of usability, we have finished revamping our web interface and completely rewritten our API. Our SPARQL endpoint now supports federated queries. All the neXtProt data are available via our user interface, API, SPARQL endpoint and FTP site, including the new PEFF 1.0 format files. Finally, the data on our FTP site is now CC BY 4.0 to promote its reuse.

The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.

neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to help researchers answer questions relevant to human proteins. To achieve this goal, neXtProt is built on a corpus containing both curated knowledge originating from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered high-throughput data pertinent to human proteins. This article presents an overview of the database and the data integration process. We also lay out the key future directions of neXtProt that we consider the necessary steps to make neXtProt the one-stop-shop for all research projects focusing on human proteins.

Every data-rich community research effort requires a clear plan for ensuring the quality of the data interpretation and comparability of analyses. To address this need within the Human Proteome Project (HPP) of the Human Proteome Organization (HUPO), we have developed through broad consultation a set of mass spectrometry data interpretation guidelines that should be applied to all HPP data contributions. For submission of manuscripts reporting HPP protein identification results, the guidelines are presented as a one-page checklist containing 15 essential points followed by two pages of expanded description of each. Here we present an overview of the guidelines and provide an in-depth description of each of the 15 elements to facilitate understanding of the intentions and rationale behind the guidelines, for both authors and reviewers. Broadly, these guidelines provide specific directions regarding how HPP data are to be submitted to mass spectrometry data repositories, how error analysis should be presented, and how detection of novel proteins should be supported with additional confirmatory evidence. These guidelines, developed by the HPP community, are presented to the broader scientific community for further discussion.