VIQoR: a web service for visually supervised protein inference and protein quantification.

MOTIVATION: In quantitative bottom-up mass spectrometry (MS)-based proteomics, the reliable estimation of protein concentration changes from peptide quantifications between different biological samples is essential. This estimation is not a single task but comprises the two processes of protein inference and protein abundance summarization. Furthermore, due to the high complexity of proteomics data and associated uncertainty about the performance of these processes, there is a demand for comprehensive visualization methods able to integrate protein with peptide quantitative data including their post-translational modifications. Hence, there is a lack of a suitable tool that provides post-identification quantitative analysis of proteins with simultaneous interactive visualization. RESULTS: In this article, we present VIQoR, a user-friendly web service that accepts peptide quantitative data of both labeled and label-free experiments and accomplishes the crucial components protein inference and summarization and interactive visualization modules, including the novel VIQoR plot. We implemented two different parsimonious algorithms to solve the protein inference problem, while protein summarization is facilitated by a well-established factor analysis algorithm called fast-FARMS followed by a weighted average summarization function that minimizes the effect of missing values. In addition, summarization is optimized by the so-called Global Correlation Indicator (GCI). We test the tool on three publicly available ground truth datasets and demonstrate the ability of the protein inference algorithms to handle shared peptides. We furthermore show that GCI increases the accuracy of the quantitative analysis in datasets with replicated design. AVAILABILITY AND IMPLEMENTATION: VIQoR is accessible at: http://computproteomics.bmb.sdu.dk/Apps/VIQoR/. The source code is available at: https://bitbucket.org/veitveit/viqor/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

ComplexBrowser: A Tool for Identification and Quantification of Protein Complexes in Large-scale Proteomics Datasets.

We have developed ComplexBrowser, an open source, online platform for supervised analysis of quantitative proteomic data (label free and isobaric mass tag based) that focuses on protein complexes. The software uses manually curated information from CORUM and Complex Portal databases to identify protein complex components. For the first time, we provide a Complex Fold Change (CFC) factor that identifies up- and downregulated complexes based on the level of complex subunits coregulation. The software provides interactive visualization of protein complexes' composition and expression for exploratory analysis and incorporates a quality control step that includes normalization and statistical analysis based on the limma package. ComplexBrowser was tested on two published studies identifying changes in protein expression within either human adenocarcinoma tissue or activated mouse T-cells. The analysis revealed 1519 and 332 protein complexes, of which 233 and 41 were found coordinately regulated in the respective studies. The adopted approach provided evidence for a shift to glucose-based metabolism and high proliferation in adenocarcinoma tissues, and the identification of chromatin remodeling complexes involved in mouse T-cell activation. The results correlate with the original interpretation of the experiments and provide novel biological details about the protein complexes affected. ComplexBrowser is, to our knowledge, the first tool to automate quantitative protein complex analysis for high-throughput studies, providing insights into protein complex regulation within minutes of analysis.

One Thousand and One Software for Proteomics: Tales of the Toolmakers of Science.

Proteomics is a highly dynamic field driven by frequent introduction of new technological approaches, leading to high demand for new software tools and the concurrent development of many methods for data analysis, processing, and storage. The rapidly changing landscape of proteomics software makes finding a tool fit for a particular purpose a significant challenge. The comparison of software and the selection of tools capable to perform a certain operation on a given type of data rely on their detailed annotation using well-defined descriptors. However, finding accurate information including tool input/output capabilities can be challenging and often heavily depends on manual curation efforts. This is further hampered by a rather low half-life of most of the tools, thus demanding the maintenance of a resource with updated information about the tools. We present here our approach to curate a collection of 189 software tools with detailed information about their functional capabilities. We furthermore describe our efforts to reach out to the proteomics community for their engagement, which further increased the catalog to >750 tools being about 70% of the estimated number of 1097 tools existing for proteomics data analysis. Descriptions of all annotated tools are available at  https://proteomics.bio.tools.

CoExpresso: assess the quantitative behavior of protein complexes in human cells.

BACKGROUND: Translational and post-translational control mechanisms in the cell result in widely observable differences between measured gene transcription and protein abundances. Herein, protein complexes are among the most tightly controlled entities by selective degradation of their individual proteins. They furthermore act as control hubs that regulate highly important processes in the cell and exhibit a high functional diversity due to their ability to change their composition and their structure. Better understanding and prediction of these functional states demands methods for the characterization of complex composition, behavior, and abundance across multiple cell states. Mass spectrometry provides an unbiased approach to directly determine protein abundances across different cell populations and thus to profile a comprehensive abundance map of proteins. RESULTS: We provide a tool to investigate the behavior of protein subunits in known complexes by comparing their abundance profiles across up to 140 cell types available in ProteomicsDB. Thorough assessment of different randomization methods and statistical scoring algorithms allows determining the significance of concurrent profiles within a complex, therefore providing insights into the conservation of their composition across human cell types as well as the identification of intrinsic structures in complex behavior to determine which proteins orchestrate complex function. This analysis can be extended to investigate common profiles within arbitrary protein groups. CoExpresso can be accessed through http://computproteomics.bmb.sdu.dk/Apps/CoExpresso . CONCLUSIONS: With the CoExpresso web service, we offer a potent scoring scheme to assess proteins for their co-regulation and thereby offer insight into their potential for forming functional groups like protein complexes.