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Petrov, P. B.

Publications and source records attributed to Petrov, P. B..

3 recordsLinked to original sources

ECMME: an atlas of selection pressures on the mammalian extracellular matrix reveals contrasting evolutionary dynamics

The extracellular matrix (ECM) is a fundamental metazoan innovation that provides structural support and regulatory cues essential for multicellular life. While core matrisome components are subject to strong functional constraints, their evolutionary dynamics at the molecular level remain incompletely characterized. Here, we present a comprehensive per-residue analysis of selection pressures across 272 human core matrisome proteins using high-quality orthologous sequences from up to 228 placental mammal species. We developed an automated pipeline integrating ortholog identification, codon-aware alignments, and site-specific selection analyses with the MEME and FUBAR methods from the HyPhy suite. Results reveal pervasive strong purifying selection across the matrisome, consistent with its structural and functional indispensability. This is accompanied by episodic positive selection and rarer pervasive positive selection, with collagens exhibiting significantly elevated episodic positive selection compared to glycoproteins and proteoglycans. To facilitate community access, we developed ECMME (ECM Molecular Evolution) browser, an intuitive open-access web resource that visualizes selection metrics plotted directly onto protein topologies. ECMME allows researchers to seamlessly browse and investigate the data, providing a powerful framework for interpreting functional sites. It is available online and requires no local installation or set-up (https://izzilab-ecmme.share.connect.posit.cloud/).

bioinformatics↗

Matrisome AnalyzeR: A suite of tools to annotate and quantify ECM molecules in big datasets across organisms

The extracellular matrix (ECM) is a complex meshwork of proteins that forms the scaffold of all tissues in multicellular organisms. It plays critical roles in all aspects of life: from orchestrating cell migration during development, to supporting tissue repair. It also plays critical roles in the etiology or progression of diseases. To study this compartment, we defined the compendium of all genes encoding ECM and ECM-associated proteins for multiple organisms. We termed this compendium the "matrisome" and further classified matrisome components into different structural or functional categories. This nomenclature is now largely adopted by the research community to annotate -omics datasets and has contributed to advance both fundamental and translational ECM research. Here, we report the development of Matrisome AnalyzeR, a suite of tools including a web-based application (https://sites.google.com/uic.edu/matrisome/tools/matrisome-analyzer) and an R package (https://github.com/Matrisome/MatrisomeAnalyzeR). The web application can be used by anyone interested in annotating, classifying, and tabulating matrisome molecules in large datasets without requiring programming knowledge. The companion R package is available to more experienced users, interested in processing larger datasets or in additional data visualization options. SUMMARY STATEMENTMatrisome AnalyzeR is a suite of tools, including a web-based app and an R package, designed to facilitate the annotation and quantification of extracellular matrix components in big datasets.

bioinformatics↗

AutoCoEv: a high-throughput in silico pipeline for revealing novel protein-protein interactions

Protein-protein communications govern cellular processes via complex regulatory networks, that are still far from being understood. Thus, identifying novel interactions between proteins can significantly facilitate our comprehension of the mechanistic principles of protein functions. Co-evolution between proteins is a sign of functional communication and, as such, provides a powerful approach to search for novel direct or indirect molecular partners. However, evolutionary analysis of large arrays of proteins, in silico, is a highly time-consuming effort, which has limited the usage of this method to protein pairs or small protein groups. Here, we developed AutoCoEv, a user-friendly computational pipeline for the search of co-evolution between a large number of proteins. By driving 15 individual programs, culminating in CAPS2 as the software for detecting co-evolution, AutoCoEv achieves seamless automation and parallelization of the workflow. Importantly, we provide a patch to CAPS2 source code to strengthen its statistical output, allowing for multiple comparisons correction and enhanced analysis of the results. We apply the pipeline to inspect co-evolution among 324 proteins identified to locate at the vicinity of the lipid rafts of B lymphocytes. We successfully detected multiple strong coevolutionary relations between the proteins, predicting many novel partners and previously unidentified clusters of functionally related molecules. We conclude that AutoCoEv, available at https://github.com/mattilalab/autocoev, can be used to predict functional interactions from large datasets in a time and cost-efficient manner.

bioinformatics↗