Y chromosome is moving out of sex determination shadow

Although sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.

Community Evaluation of Glycoproteomics Informatics Solutions Reveals High-Performance Search Strategies of Glycopeptide Data

Glycoproteome profiling (glycoproteomics) remains a considerable analytical challenge that hinders rapid progress in glycobiology. The complex tandem mass spectra generated from glycopeptide mixtures require sophisticated analysis pipelines for structural determination. Diverse informatics solutions aiding the process have appeared, but their relative strengths and weaknesses remain untested. Conducted through the Human Proteome Project – Human Glycoproteomics Initiative, this community study comprising both developers and expert users of glycoproteomics software is the first to evaluate the relative performance of current informatics solutions for comprehensive glycopeptide analysis. High-quality LC-MS/MS-based glycoproteomics datasets of N- and O-glycopeptides from serum proteins were shared with all teams. The relative team performance for efficient glycopeptide data analysis was systematically established through multiple orthogonal performance tests. Excitingly, several high-performance glycoproteomics informatics solutions and tools displaying a considerable performance potential were identified. While the study illustrated that significant informatics challenges remain in the analysis of glycopeptide data as indicated by a high discrepancy between the reported glycopeptides, a substantial list of commonly reported high-confidence glycopeptides could be extracted from the team reports. Further, the team performance profiles were correlated to the many study variables, which revealed important performance-associated search settings and search output variables, some intuitive others unexpected. This study concludes that diverse informatics solutions for comprehensive glycopeptide data analysis exist within the community, points to several high-performance search strategies, and specifies key variables that may guide future software developments and assist the experimental decision-making of practitioners in glycoproteomics.

A high-stringency blueprint of the human proteome

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.

Empowering Shotgun Mass Spectrometry with 2DE: A HepG2 Study

One of the major goals of the Chromosome-Centric Human Proteome Project (C-HPP) is to catalog and annotate a myriad of heterogeneous proteoforms, produced by ca. 20 thousand genes. To achieve a detailed and personalized understanding into proteomes, we suggest using a customized RNA-seq library of potential proteoforms, which includes aberrant variants specific to certain biological samples. Two-dimensional electrophoresis coupled with high-performance liquid chromatography allowed us to downgrade the difficulty of biological mixing following shotgun mass spectrometry. To benchmark the proposed pipeline, we examined heterogeneity of the HepG2 hepatoblastoma cell line proteome. Data are available via ProteomeXchange with identifier PXD018450.