The Human Proteome Project: Current State and Future Direction

Abstract

After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and crossanalyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators.

Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)

“…For example, analysis of data from the human genome project has led to the identification of new genetic causes of male infertility (5), particularly those associated with specific defects in semen parameters, testicular pathologies (6), epididymal regulatory elements for genes coordinating epididymal function (7), and cell-free seminal DNA in human semen (8). However, a combination of alternative splicing and posttranslational modifications (PTMs) 1 can yield an estimated one million different protein species that may vary with time and location as well as according to physiologic, pathologic, and pharmacologic perturbations (9) and that hold an even greater promise at the protein level. In somatic cells, such diversity is required for the selected activation and inhibition of signaling pathways in a context-appropriate manner.…”

PUEPro: A Computational Pipeline for Prediction of Urine Excretory Proteins

“…Several datasets of proteins have been identified in human urine, including those in the Sys-BodyFluid database [12] and the Human Proteome Project (HPP) database [13]. The Sys-BodyFluid database consists of 1,941 distinct human proteins that have been experimentally identified in nine urinary proteomic studies.…”

“…The present study extends the previous study by including novel capabilities for identification of origins of detected proteins in urine in addition to an improved prediction tool for proteins that are urine excretory. Our study utilizes a few data sources of urinary proteins to build a predictor for such proteins, including those given in [12][13][14][15][16]. The current knowledge is: 70% of the urinary proteins originate from the kidney and the urinary tracts, and the remaining 30% are filtered from blood circulation by the glomerulus [17].…”

Evolution of Proteomic Methods for Analysis of Complex Biological Samples – Implications for Personalized Medicine

“…Surprisingly, the total number of protein coding genes, only approximately 20,300, was substantially lower than expected, with increased complexity presumably due to splice variants, and post-translational modifications. Following on from this ground-breaking work, is the recent establishment of the Human Proteome Project which aims to map the human proteome (Legrain et al, 2011). At present, of the protein-coding genes in humans identified in the human genome, approximately one third have not been detected at the protein level, while for many others, basic information such as abundance, sub-cellular localization, or function are unknown.…”