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HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration
Huntington's disease (HD) is a progressive neurological disorder that is caused by polyglutamine expansion of the huntingtin (HTT) protein. With the hope to uncover key modifiers of disease, a focus of the field of HD research has been on characterizing HTT-interacting proteins (HIPs) and the e...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540350/ https://www.ncbi.nlm.nih.gov/pubmed/35932982 http://dx.doi.org/10.1016/j.mcpro.2022.100275 |
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author | Kennedy, Michelle A. Greco, Todd M. Song, Bokai Cristea, Ileana M. |
author_facet | Kennedy, Michelle A. Greco, Todd M. Song, Bokai Cristea, Ileana M. |
author_sort | Kennedy, Michelle A. |
collection | PubMed |
description | Huntington's disease (HD) is a progressive neurological disorder that is caused by polyglutamine expansion of the huntingtin (HTT) protein. With the hope to uncover key modifiers of disease, a focus of the field of HD research has been on characterizing HTT-interacting proteins (HIPs) and the effect of the HTT polyglutamine expansion on the cellular omics landscape. However, while hundreds of studies have uncovered over 3000 potential HIPs to date, a means to interrogate these complementary interaction and omics datasets does not exist. The lack of a unified platform for exploring this breadth of potential HIPs and associated omics data represents a substantial barrier toward understanding the impact of HTT polyQ expansion and identifying interactions proximal to HD pathogenesis. Here, we describe the development of a web-based platform called HTT-OMNI (HTT OMics and Network Integration). This application facilitates the visualization and exploration of ∼3400 potential HTT interactors (from the HINT database) and their associated polyQ-dependent omics measurements, such as transcriptome and proteome abundances. Additionally, HTT-OMNI allows for the integration of user-generated datasets with existing HIPs and omic measurements. We first demonstrate the utility of HTT-OMNI for filtering existing HTT PPIs based on a variety of experimental metadata parameters, highlighting its capacity to select for HIPs detected in specific model organisms and tissues. Next, we leverage our application to visualize the relationships between HTT PPIs, genetic disease modifiers, and their multiomic landscape. Finally, we generate and analyze a previously unreported dataset of HTT PPIs, aimed at defining tissue-specific HTT interactions and the polyQ-dependent modulation of their relative stabilities in the cortex and striatum of HD mouse models. |
format | Online Article Text |
id | pubmed-9540350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-95403502022-10-14 HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration Kennedy, Michelle A. Greco, Todd M. Song, Bokai Cristea, Ileana M. Mol Cell Proteomics Technological Innovation and Resources Huntington's disease (HD) is a progressive neurological disorder that is caused by polyglutamine expansion of the huntingtin (HTT) protein. With the hope to uncover key modifiers of disease, a focus of the field of HD research has been on characterizing HTT-interacting proteins (HIPs) and the effect of the HTT polyglutamine expansion on the cellular omics landscape. However, while hundreds of studies have uncovered over 3000 potential HIPs to date, a means to interrogate these complementary interaction and omics datasets does not exist. The lack of a unified platform for exploring this breadth of potential HIPs and associated omics data represents a substantial barrier toward understanding the impact of HTT polyQ expansion and identifying interactions proximal to HD pathogenesis. Here, we describe the development of a web-based platform called HTT-OMNI (HTT OMics and Network Integration). This application facilitates the visualization and exploration of ∼3400 potential HTT interactors (from the HINT database) and their associated polyQ-dependent omics measurements, such as transcriptome and proteome abundances. Additionally, HTT-OMNI allows for the integration of user-generated datasets with existing HIPs and omic measurements. We first demonstrate the utility of HTT-OMNI for filtering existing HTT PPIs based on a variety of experimental metadata parameters, highlighting its capacity to select for HIPs detected in specific model organisms and tissues. Next, we leverage our application to visualize the relationships between HTT PPIs, genetic disease modifiers, and their multiomic landscape. Finally, we generate and analyze a previously unreported dataset of HTT PPIs, aimed at defining tissue-specific HTT interactions and the polyQ-dependent modulation of their relative stabilities in the cortex and striatum of HD mouse models. American Society for Biochemistry and Molecular Biology 2022-08-03 /pmc/articles/PMC9540350/ /pubmed/35932982 http://dx.doi.org/10.1016/j.mcpro.2022.100275 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Technological Innovation and Resources Kennedy, Michelle A. Greco, Todd M. Song, Bokai Cristea, Ileana M. HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title | HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title_full | HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title_fullStr | HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title_full_unstemmed | HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title_short | HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration |
title_sort | htt-omni: a web-based platform for huntingtin interaction exploration and multi-omics data integration |
topic | Technological Innovation and Resources |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9540350/ https://www.ncbi.nlm.nih.gov/pubmed/35932982 http://dx.doi.org/10.1016/j.mcpro.2022.100275 |
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