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. 2020 Jan 8;48(D1):D1136-D1144.
doi: 10.1093/nar/gkz849.

MatrisomeDB: the ECM-protein knowledge database

Affiliations

MatrisomeDB: the ECM-protein knowledge database

Xinhao Shao et al. Nucleic Acids Res. .

Abstract

The extracellular matrix (ECM) is a complex and dynamic meshwork of cross-linked proteins that supports cell polarization and functions and tissue organization and homeostasis. Over the past few decades, mass-spectrometry-based proteomics has emerged as the method of choice to characterize the composition of the ECM of normal and diseased tissues. Here, we present a new release of MatrisomeDB, a searchable collection of curated proteomic data from 17 studies on the ECM of 15 different normal tissue types, six cancer types (different grades of breast cancers, colorectal cancer, melanoma, and insulinoma) and other diseases including vascular defects and lung and liver fibroses. MatrisomeDB (http://www.pepchem.org/matrisomedb) was built by retrieving raw mass spectrometry data files and reprocessing them using the same search parameters and criteria to allow for a more direct comparison between the different studies. The present release of MatrisomeDB includes 847 human and 791 mouse ECM proteoforms and over 350 000 human and 600 000 mouse ECM-derived peptide-to-spectrum matches. For each query, a hierarchically-clustered tissue distribution map, a peptide coverage map, and a list of post-translational modifications identified, are generated. MatrisomeDB is the most complete collection of ECM proteomic data to date and allows the building of a comprehensive ECM atlas.

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Figures

Figure 1.
Figure 1.
Examples of database query result showing hierarchically-clustered protein distribution heatmaps. (A) Confidence-score-based heatmap generated upon querying ‘COL4’ and selecting ‘HUMAN’ in the Species option box. Results show the tissue distribution of the 6 collagen-IV protein chains encoded by the COL4A1, COL4A2, COL4A3, COL4A4, COL4A5 and COL4A6 genes. The color code indicates the confidence score from high (dark blue) to low (light yellow). Clicking on the heatmap itself or on the link located above the heatmap (red arrow) will open a detailed heatmap and a link to download the data in .csv format. The ‘Export result as CSV’ button (orange arrow) allows users to download the complete results. (B) Total-Ion-Current-based heatmap generated upon querying ‘COL4’ and selecting ‘HUMAN’ in the Species option box, and accessible from the detailed heatmap page. The color code indicates the confidence score from high (dark blue) to low (light yellow).
Figure 2.
Figure 2.
Peptide coverage map. (A) Peptide coverage map of Nidogen 1 in the glomerular basement membrane dataset. The color code indicates the peptide-spectrum match frequency from high (dark blue) to low (light blue). (B) Peptide coverage map of Nidogen 1 across all the datasets (11 tissues and 31 sample types) in which Nidogen 1 was detected. The color code indicates the peptide-spectrum match frequency from high (dark blue) to low (light blue).
Figure 3.
Figure 3.
Building an ECM Atlas. (A) Experimental coverage of the in-silico predicted matrisome. Bar chart represents, for each matrisome category (x axis), the percentage of the in-silico predicted genes encoding proteins detected in the proteomic studies included in MatrisomeDB (y axis). The actual number of proteins detected is indicated inside the bars. The percentages indicated above the bar chart indicate the increase in coverage with the updated database. (B) Hierarchically-clustered tissue distribution heatmap of all 30 proteoglycans detected and reported in MatrisomeDB. The color code indicates the confidence score from high (dark blue) to low (light yellow).

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