HUPO Brain Proteome Project Pilot Studies: bioinformatics at work

The data acquisition phase of initial pilot studies (human and mouse brain samples) of the Human Proteome Organisation (HUPO) Brain Proteome Project (BPP) is now complete and the data generated by the participating laboratories has been submitted to the central Data Collection Center. The BPP Bioinformatics Group met on 8th April 2005 at the European Bioinformatics Institute (Hinxton, UK) to discuss strategies for the reanalysis of the pooled data from all the participating laboratories. A summary of the results of the data reprocessing will be presented at the 4th HUPO World Congress that will be held in August/September 2005.     

The HUPO Brain Proteome Project jamboree: centralised summary of the pilot studies

The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post-lab analyses of the data produced in the HUPO BPP pilot studies. On January 9-11, 2006 the members as well as invited analysts came together at the European Bioinformatics Institute in Hinxton, UK for the pilot studies jamboree. The results of the reprocessing were presented and tasks forces were initiated to compile, to interpret and to summarise the data obtained.     

Automated reprocessing pipeline for searching heterogeneous mass spectrometric data of the HUPO Brain Proteome Project pilot phase

The newly available techniques for sensitive proteome analysis and the resulting amount of data require a new bioinformatics focus on automatic methods for spectrum reprocessing and peptide/protein validation. Manual validation of results in such studies is not feasible and objective enough for quality relevant interpretation. The necessity for tools enabling an automatic quality control is, therefore, important to produce reliable and comparable data in such big consortia as the Human Proteome Organization Brain Proteome Project. Standards and well-defined processing pipelines are important for these consortia. We show a way for choosing the right database model, through collecting data, processing these with a decoy database and end up with a quality controlled protein list merged from several search engines, including a known false-positive rate.     

Ten Years of Standardizing Proteomic Data: A Report on the HUPO-PSI Spring Workshop: April 12-14th, 2012, San Diego, USA

The Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) was established in 2002 with the aim of defining community standards for data representation in proteomics and facilitating data comparison, exchange and verification. Over the last 10 years significant advances have been made, with common data standards now published and implemented in the field of both mass spectrometry and molecular interactions. The 2012 meeting further advanced this work, with the mass spectrometry groups finalising approaches to capturing the output from recent developments in the field, such as quantitative proteomics and SRM. The molecular interaction group focused on improving the integration of data from multiple resources. Both groups united with a guest work track, organized by the HUPO Technology/Standards Committee, to formulate proposals for data submissions from the HUPO Human Proteome Project and to start an initiative to collect standard experimental protocols.     

Towards standard protocols and guidelines for urine proteomics: a report on the Human Kidney and Urine Proteome Project (HKUPP) symposium and workshop, 6 October 2007, Seoul, Korea and 1 November 2007, San Francisco, CA, USA

The Human Kidney and Urine Proteome Project (HKUPP) was initiated in 2005 to promote proteomics research in the nephrology field, to better understand kidney functions as well as pathogenic mechanisms of kidney diseases, and to define novel biomarkers and therapeutic targets. This project was first approved in 2005 by the Human Proteome Organisation (HUPO) as a Kidney Disease Initiative under an umbrella of the HUPO Disease Biomarker Initiative (DBI), and more recently was approved as the HKUPP Initiative in 2007. Several sub-projects have been planned to achieve the ultimate goals. The most pressing is the establishment of "standard protocols and guidelines for urine proteome analysis". This sub-project had been extensively discussed during the first HKUPP symposium (during 6(th) HUPO Annual World Congress--October 2007, Seoul, Korea) and second workshop (during 40(th) American Society of Nephrology Renal Week--November 2007, San Francisco, CA, USA). Additional data and references have been collected after the symposium and workshop. An initial draft of standard protocols and guidelines for proteome analysis of non-proteinuric urine (urine protein excretion < or =150 mg/day) will soon be released as the first HKUPP product.     

Analyzing large-scale proteomics projects with latent semantic indexing

Since the advent of public data repositories for proteomics data, readily accessible results from high-throughput experiments have been accumulating steadily. Several large-scale projects in particular have contributed substantially to the amount of identifications available to the community. Despite the considerable body of information amassed, very few successful analyses have been performed and published on this data, leveling off the ultimate value of these projects far below their potential. A prominent reason published proteomics data is seldom reanalyzed lies in the heterogeneous nature of the original sample collection and the subsequent data recording and processing. To illustrate that at least part of this heterogeneity can be compensated for, we here apply a latent semantic analysis to the data contributed by the Human Proteome Organization's Plasma Proteome Project (HUPO PPP). Interestingly, despite the broad spectrum of instruments and methodologies applied in the HUPO PPP, our analysis reveals several obvious patterns that can be used to formulate concrete recommendations for optimizing proteomics project planning as well as the choice of technologies used in future experiments. It is clear from these results that the analysis of large bodies of publicly available proteomics data by noise-tolerant algorithms such as the latent semantic analysis holds great promise and is currently underexploited.     

The HUPO Brain Proteome project wish list--summary of the 9(th) HUPO BPP Workshop 9-10 January 2008, Barbados

The Human Brain Proteome Project (HUPO BPP) aims at advancing knowledge and the understanding of neurodiseases and aging with the purpose of identifying prognostic and diagnostic biomarkers, as well as to push new diagnostic approaches and medications. The participating groups meet in semi-annual workshops to discuss the progress, as well as the needs, within the field of proteomics. The 9(th) HUPO BPP workshop took place in Barbados from 9-10 January, 2008. Discussing the future HUPO BPP Roadmap, the attendees drafted the so called HUPO BPP wish list containing timelines, suggestions and missions. This wish list will be updated regularly and will serve as a guideline for the next phase.     

A comparison of the HUPO Brain Proteome Project pilot with other proteomics studies

The pilot phase of the Brain Proteome Project (BPP), the Human Proteome Organization (HUPO) initiative that focuses on studies of the brain of both humans and mice, has now been completed. Participating laboratories studied the proteomes of two human samples derived from biopsy and autopsy as well as three mouse samples from various developmental stages. With the combined and centrally reprocessed data now available, a comparison in terms of protein identifications and project organization is made between the HUPO BPP pilot and three other proteomics studies: the HUPO Plasma Proteome Project (PPP) pilot, a proteome of human blood platelets and a recently published comprehensive mouse proteome. Finally, as any comparison between large-scale proteomics datasets is decidedly non-trivial, we also evaluate and discuss several ways to go about comparing such different result sets.     

A standardized framing for reporting protein identifications in mzIdentML 1.2

Inferring which protein species have been detected in bottom‐up proteomics experiments has been a challenging problem for which solutions have been maturing over the past decade. While many inference approaches now function well in isolation, comparing and reconciling the results generated across different tools remains difficult. It presently stands as one of the greatest barriers in collaborative efforts such as the Human Proteome Project and public repositories such as the PRoteomics IDEntifications (PRIDE) database. Here we present a framework for reporting protein identifications that seeks to improve capabilities for comparing results generated by different inference tools. This framework standardizes the terminology for describing protein identification results, associated with the HUPO‐Proteomics Standards Initiative (PSI) mzIdentML standard, while still allowing for differing methodologies to reach that final state. It is proposed that developers of software for reporting identification results will adopt this terminology in their outputs. While the new terminology does not require any changes to the core mzIdentML model, it represents a significant change in practice, and, as such, the rules will be released via a new version of the mzIdentML specification (version 1.2) so that consumers of files are able to determine whether the new guidelines have been adopted by export software.     

Report of the 9th HLPP Workshop October 2007, Seoul, Korea

The Human Liver Proteome Project is one of the Human Proteome Initiatives launched by Human Proteome Organization (HUPO). Major achievements of the project have been obtained under the efforts of international collaboration with all the participants since it was formally proposed in 2002. Its updated progresses were presented in the latest workshop held in conjunction with the sixth HUPO World Congress in October, 2007, Seoul, Korea. Furthermore, four topics related to the project as well as other initiatives were lively discussed among all the attendees.     

Improvement of the physical properties of reprocessed paper by using biological treatment with modified cellulase

A primary need for waste paper reprocessing is to preserve optical properties and the physical strength of the paper fibers. In this study, modified cellulase with copolymer, polyethylene oxide (PEO) derivatives and maleic anhydride (MA) was applied to the reprocessing of mixed office waste (MOW). Modified cellulase was prepared by a chemical reaction between amino groups of the cellulase and the MA functional groups of the copolymer. In MOW reprocessing, modified cellulase improved several physical properties of the paper including freeness, optical properties, and physical strength compared to the conventional process. Even though native cellulase improved the physical properties, paper treated with modified cellulase exhibited an increase in physical properties such as tensile strength and internal bond over those of unmodified cellulase. From these results, modified cellulase method is a new biological treatment that will save pulp resources, which are added to waste paper reprocessing to maintain the strength of paper.     

Proteome biology of stem cells

The notion that integration of cutting-edge technologies in stem cell research would be enhanced by proteomic analyses has emanated from rapid advances in proteome technology. These advances have increased the probability that basic properties of stem cells will be elucidated more effectively, leading to acceleration toward novel stem cell therapies. We have therefore sought to establish a world-wide alliance of proteomics and stem cell researchers, which has resulted in the foundation of an initiative supported by the Human Proteome Organisation (HUPO) and the International Society for Stem Cell Research (ISSCR) called the Proteome Biology of Stem Cells Initiative. Here we report on the rationale and goals of this initiative.     

Towards data management of the HUPO Human Brain Proteome Project pilot phase

The pilot phase of the Human Brain Proteome Project as a part of the Human Proteome Organisation has just been started. In two pilot studies, 18 different laboratories are analyzing mouse brains of three age stages and human brain autopsy versus biopsy material, respectively. The overall aim is to elucidate the portfolio of available techniques as well as to elaborate common standards. As a first step, it was decided to use the common bioinformatics platform ProteinScape that was introduced to the participating groups in a two day course in Bochum, Germany.     

The human proteome project: current state and future direction

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 cross-analyses 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.     

A functional annotation of subproteomes in human plasma

The data collected by Human Proteome Organization's Plasma Proteome Pilot project phase was analyzed by members of our working group. Accordingly, a functional annotation of the human plasma proteome was carried out. Here, we report the findings of our analyses. First, bioinformatic analyses were undertaken to determine the likely sources of plasma proteins and to develop a protein interaction network of proteins identified in this project. Second, annotation of these proteins was performed in the context of functional subproteomes involved in the coagulation pathway, the mononuclear phagocytic system, the inflammation pathway, the cardiovascular system, and the liver; as well as the subset of proteins associated with DNA binding activities. Our analyses contributed to the Plasma Proteome Database (http://www.plasmaproteomedatabase.org), an annotated database of plasma proteins identified by HPPP as well as from other published studies. In addition, we address several methodological considerations including the selective enrichment of post-translationally modified proteins by the use of multi-lectin chromatography as well as the use of peptidomic techniques to characterize the low molecular weight proteins in plasma. Furthermore, we have performed additional analyses of peptide identification data to annotate cleavage of signal peptides, sites of intra-membrane proteolysis and post-translational modifications. The HPPP-organized, multi-laboratory effort, as described herein, resulted in much synergy and was essential to the success of this project.     

Proteomics of Halophilic archaea

Halophilic archaea is a member of the Halobacteriacea family, the only family in the Halobacteriales order. Most Halophilic archaea require 1.5M NaCl both to grow and retain the structural integrity of the cells. The proteins of these organisms have thus been adapted to be active and stable in the hypersaline condition. Consequently, the unique properties of these biocatalysts have resulted in several novel applications in industrial processes. Halophilic archaea are also to be useful for bioremediation of hypersaline environment. Proteome data have expended enormously with the significant advance recently achieved in two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). The whole genome sequencing of Halobacterium species NRC-1 was completed and this would also provide tremendous help to analyze the protein mass data from the similar strain Halobacterium salinarum. Proteomics coupled with genomic databases now has become a basic tool to understand or identify the function of genes and proteins. In addition, the bioinformatics approach will facilitate to predict the function of novel proteins of Halophilic archaea. This review will discuss current proteome study of Halophilic archaea and introduce the efficient procedures for screening, predicting, and confirming the function of novel halophilic enzymes.     

蛋白质组研究的现状与展望

蛋白质组是后基因组时代出现的一个新兴研究领域。蛋白质组的研究主要是先通过双向凝胶电泳等方法分离蛋白质,然后用质谱等技术进行鉴定。它是后基因组重要的研究方向之一,具有巨大的商业应用前景,将会推动整个生命科学的发展。蛋白质组研究取得了很大进展,已经成为生物技术中的一个重要领域。     

The 2009 Human Liver Proteome Project (HLPP) Workshop 26 September 2009, Toronto,Canada

The Human Liver Proteome Project (HLPP) was formally launched by HUPO in 2002. The 11th HLPP Workshop was held on September 26th, 2009 during the 8th HUPO World Congress in Toronto, Canada. The representative progresses were presented from four groups. Subsequently, the workshop ended with a lively discussion on four topics related to the project as well as other initiatives.