piNET: a versatile web platform for downstream analysis and visualization of proteomics data

Shamsaei, Behrouz; Chojnacki, Szymon; Pilarczyk, Marcin; Najafabadi, Mehdi Fazel; Chen, Chuming; Ross, Karen; Matlock, Andrea; Muhlich, Jeremy; Vidović, Dušica; Sharma, Vagisha; Vasiliauskas, Juozas; Jaffe, Jacob D.; MacCoss, Michael J.; Wu, Cathy; Pillai, Ajay S.; Ma’ayan, Avi; Schürer, Stephan C.; Medvedovic, Mario; Meller, Jarek

doi:10.1101/607432

Cited by 4 publications

(5 citation statements)

References 30 publications

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“…Additional analyses were performed using piNET (http://pinet-server.org/), a tool developed to provide further assessment of region-specific protein networks, including targeted analyses of kinase signaling pathways [40].…”

Section: Clustering Analyses and Generationmentioning

confidence: 99%

Region-Specific PSD-95 Interactomes Contribute to Functional Diversity of Excitatory Synapses in Human Brain

Funk

Labilloy

Reigle

et al. 2020

Preprint

Self Cite

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Running title -PSD-95 protein-protein interactions in human brainThe overarching goal of this exploratory study is to link subcellular microdomain specific protein-protein interactomes with big data analytics. We isolated postsynaptic density-95 (PSD-95) complexes from four human brain regions and compared their protein interactomes using multiple bioinformatics techniques. We demonstrate that human brain regions have unique postsynaptic protein signatures that may be used to interrogate perturbagen databases. Assessment of our hippocampal signature using the iLINCS database yielded several compounds with recently characterized "off target" effects on protein-protein interactions in the posynaptic density compartment. Acknowledgments:We would like to thank all those that have supported this research: the L.I.F.E. Foundation, UCNI pilot award, Lindsay Brinkmeyer Schizophrenia Research Fund, Center for Clinical and Translational Science Training (CCTST), and NIH grant MH107916. The MS data was acquired in the University of Cincinnati Proteomics Laboratory on a mass spectrometer funded in part through the NIH S10 shared instrumentation grant RR027015.Altering the expression of PSD-95 protein significantly changes synaptic structure and function, including molecular correlates of learning and memory, long-term potentiation (LTP) and long-term depression (LTD). For example, PSD-95 overexpression increases the amplitude of excitatory postsynaptic currents (EPSCs), to the extent that additional stimulus is unable to further strengthen LTP [13][14][15][16][17]. In contrast, PSD-95 knockdown disrupts postsynaptic density structure and suppresses EPSCs, consistent with a role for PSD-95 in synaptic fidelity [18][19][20]. Further highlighting the importance of PSD-95 in the synapse, knockout of PSD-95 in mice and genomic variants within postsynaptic density hub proteins are particularly implicated in neuropsychiatric disorders such as schizophrenia and autism [21,22].To investigate excitatory postsynaptic protein hubs, we targeted PSD-95 due to its high level of localization to the postsynaptic density (~95%), its well-characterized role as a hub protein, and the large number of constituents in its protein interactome (~1000) [23][24][25]. We designed a series of experiments to examine brain region-specific excitatory postsynaptic proteomes to answer the following questions. 1) Do postsynaptic protein-protein interactions differ by brain region? 2) Can we accurately detect and separate samples based on these differences? and 3) Can region-specific protein interactomes inform functional differences? For these experiments we used four human brain regions (anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus (HPC), and superior temporal gyrus (STG)) from 3 well-matched control male subjects from the Alabama Brain Collection. A total of 289 proteins were identified as part of a PSD-95 protein interactome that were present across all four brain regions.We hypothesize that there is region-specific ...

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Section: Clustering Analyses and Generationmentioning

confidence: 99%

Region-Specific PSD-95 Interactomes Contribute to Functional Diversity of Excitatory Synapses in Human Brain

Funk

Labilloy

Reigle

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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“…PTMapper, PhosphoPath, and PTMOracle allow users to covisualize and coanalyze PTM data in the realm of PPI networks and helps improve our understanding of PTM-associated relationships. Analogously, piNET, another PTM-centric visualization tool, maps peptides to proteins, performs upstream analysis of PTM sites, and conducts pathway analysis. Despite this, however, there is a sparsity of tools that (1) perform protein-centric PPIs and functional enrichment analysis while maintaining the protein-gene relationship from public databases which predominantly contains gene-centric information, (2) address ambiguity arising from combining data retrieved through various independent databases, and (3) simultaneously explore the regulatory role of PTMs and their involvement in PPIs and biological function.…”

Section: Introductionmentioning

confidence: 99%

PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks

Sundararaman

Robinson

et al. 2020

J. Am. Soc. Mass Spectrom.

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Recent surges in mass spectrometry-based proteomics studies demand a concurrent rise in speedy and optimized data processing tools and pipelines. Although several stand-alone bioinformatics tools exist that provide protein−protein interaction (PPI) data, we developed Protein Interaction Network Extractor (PINE) as a fully automated, user-friendly, graphical user interface application for visualization and exploration of global proteome and post-translational modification (PTM) based networks. PINE also supports overlaying differential expression, statistical significance thresholds, and PTM sites on functionally enriched visualization networks to gain insights into proteome-wide regulatory mechanisms and PTM-mediated networks. To illustrate the relevance of the tool, we explore the total proteome and its PTM-associated relationships in two different nonalcoholic steatohepatitis (NASH) mouse models to demonstrate different context-specific case studies. The strength of this tool relies in its ability to (1) perform accurate protein identifier mapping to resolve ambiguity, (2) retrieve interaction data from multiple publicly available PPI databases, and (3) assimilate these complex networks into functionally enriched pathways, ontology categories, and terms. Ultimately, PINE can be used as an extremely powerful tool for novel hypothesis generation to understand underlying disease mechanisms.

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“…27,28 Other research groups have released web applications that facilitate online exploration and sharing of MS datasets. [29][30][31][32][33][34] The next generation of tools should be available to non-programmers, able to convert general multi-omics MS data into a cloud-friendly format, comprehensively interfaced with interactive visualizations, and sharable with collaborators for intuitive hands-on exploration.…”

Section: Introductionmentioning

confidence: 99%

Argonaut: A Web Platform for Collaborative Multi-omic Data Visualization and Exploration

et al. 2020

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SUMMARY Researchers now generate large multi-omic datasets using increasingly mature mass spectrometry techniques at an astounding pace, facing new challenges of “Big Data” dissemination, visualization, and exploration. Conveniently, web-based data portals accommodate the complexity of multi-omic experiments and the many experts involved. However, developing these tailored companion resources requires programming expertise and knowledge of web server architecture—a substantial burden for most. Here, we describe Argonaut, a simple, code-free, and user-friendly platform for creating customizable, interactive data-hosting websites. Argonaut carries out real-time statistical analyses of the data, which it organizes into easily sharable projects. Collaborating researchers worldwide can explore the results, visualized through popular plots, and modify them to streamline data interpretation. Increasing the pace and ease of access to multi-omic data, Argonaut aims to propel discovery of new biological insights. We showcase the capabilities of this tool using a published multi-omics dataset on the large mitochondrial protease deletion collection.

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piNET: a versatile web platform for downstream analysis and visualization of proteomics data

Cited by 4 publications

References 30 publications

Region-Specific PSD-95 Interactomes Contribute to Functional Diversity of Excitatory Synapses in Human Brain

Region-Specific PSD-95 Interactomes Contribute to Functional Diversity of Excitatory Synapses in Human Brain

PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks

Argonaut: A Web Platform for Collaborative Multi-omic Data Visualization and Exploration

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