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      Automated annotation and visualisation of high-resolution spatial proteomic mass spectrometry imaging data using HIT-MAP

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          Abstract

          Spatial proteomics has the potential to significantly advance our understanding of biology, physiology and medicine. Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is a powerful tool in the spatial proteomics field, enabling direct detection and registration of protein abundance and distribution across tissues. MALDI-MSI preserves spatial distribution and histology allowing unbiased analysis of complex, heterogeneous tissues. However, MALDI-MSI faces the challenge of simultaneous peptide quantification and identification. To overcome this, we develop and validate HIT-MAP (High-resolution Informatics Toolbox in MALDI-MSI Proteomics), an open-source bioinformatics workflow using peptide mass fingerprint analysis and a dual scoring system to computationally assign peptide and protein annotations to high mass resolution MSI datasets and generate customisable spatial distribution maps. HIT-MAP will be a valuable resource for the spatial proteomics community for analysing newly generated and retrospective datasets, enabling robust peptide and protein annotation and visualisation in a wide array of normal and disease contexts.

          Abstract

          MALDI-mass spectrometry imaging (MSI) can reveal the distribution of proteins in tissues but tools for protein identification and annotation are sparse. Here, the authors develop an open-source bioinformatic workflow for false discovery rate-controlled protein annotation and spatial mapping from MALDI-MSI data.

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          The PRIDE database and related tools and resources in 2019: improving support for quantification data

          Abstract The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world’s largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3 years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas.
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            A statistical model for identifying proteins by tandem mass spectrometry.

            A statistical model is presented for computing probabilities that proteins are present in a sample on the basis of peptides assigned to tandem mass (MS/MS) spectra acquired from a proteolytic digest of the sample. Peptides that correspond to more than a single protein in the sequence database are apportioned among all corresponding proteins, and a minimal protein list sufficient to account for the observed peptide assignments is derived using the expectation-maximization algorithm. Using peptide assignments to spectra generated from a sample of 18 purified proteins, as well as complex H. influenzae and Halobacterium samples, the model is shown to produce probabilities that are accurate and have high power to discriminate correct from incorrect protein identifications. This method allows filtering of large-scale proteomics data sets with predictable sensitivity and false positive identification error rates. Fast, consistent, and transparent, it provides a standard for publishing large-scale protein identification data sets in the literature and for comparing the results obtained from different experiments.
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              Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

              Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.
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                Author and article information

                Contributors
                t.cox@garvan.org.au
                ac.grey@auckland.ac.nz
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                28 May 2021
                28 May 2021
                2021
                : 12
                : 3241
                Affiliations
                [1 ]GRID grid.9654.e, ISNI 0000 0004 0372 3343, Mass Spectrometry Hub, , University of Auckland, ; Auckland, New Zealand
                [2 ]GRID grid.9654.e, ISNI 0000 0004 0372 3343, School of Biological Sciences, , University of Auckland, ; Auckland, New Zealand
                [3 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, , UNSW Sydney, ; Sydney, NSW Australia
                [4 ]GRID grid.117476.2, ISNI 0000 0004 1936 7611, School of Life Sciences, , University of Technology Sydney, ; Sydney, NSW Australia
                [5 ]GRID grid.9654.e, ISNI 0000 0004 0372 3343, University of Auckland, School of Biological Sciences, ; Auckland, New Zealand
                [6 ]GRID grid.152326.1, ISNI 0000 0001 2264 7217, Department of Biochemistry, , Vanderbilt University, ; Nashville, TN USA
                [7 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, St Vincent’s Clinical School, Faculty of Medicine, , UNSW Sydney, ; Sydney, NSW Australia
                Author information
                http://orcid.org/0000-0003-2217-5525
                http://orcid.org/0000-0002-0666-9405
                http://orcid.org/0000-0001-9294-1745
                http://orcid.org/0000-0002-1540-1080
                Article
                23461
                10.1038/s41467-021-23461-w
                8163805
                34050164
                fc3c02cf-252d-48cc-9c4e-cfe473f4a378
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 October 2020
                : 29 April 2021
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                © The Author(s) 2021

                Uncategorized
                peptides,imaging,mass spectrometry,proteome informatics
                Uncategorized
                peptides, imaging, mass spectrometry, proteome informatics

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