A Coordinated Approach by Public Domain Bioinformatics Resources to Aid the Fight Against Alzheimer’s Disease Through Expert Curation of Key Protein Targets

Breuza, Lionel; Arighi, Cecilia N.; Argoud-Puy, Ghislaine; Casals-Casas, Cristina; Estreicher, Anne; Famiglietti, Maria Livia; Georghiou, George P.; Gos, Arnaud; Gruaz-Gumowski, Nadine; Hinz, Ursula; Hyka‐Nouspikel, Nevila; Kramarz, Barbara; Lovering, Ruth C.; Lussi, Yvonne C.; Magrane, Michele; Masson, Patrick; Perfetto, Livia; Poux, Sylvain; Rodrı́guez-López, Milagros; Stoeckert, Christian J.; Sundaram, Shyamala; Wang, Li-San; Wu, Elizabeth; Orchard, Sandra

doi:10.3233/jad-200206

Cited by 9 publications

(12 citation statements)

References 76 publications

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“…Another recent example of a disease-focused curation effort has been the update of records relating to Alzheimer's disease, including proteins containing a disease-related amino-acid variant, their interacting partners and model organism proteins important for our understanding of disease initiation and progression. This work has been supported by clinical researchers active in the field who contributed to a number of workshops held in both the USA and UK and have suggested key protein targets for focused curation ( 22 , 23 ) and provided valuable user input into how this data should be accessed.…”

Section: Progress and New Developmentsmentioning

confidence: 99%

UniProt: the universal protein knowledgebase in 2021

Bateman¹,

Martin²,

Orchard³

et al. 2020

Nucleic Acids Research

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The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

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Section: Progress and New Developmentsmentioning

confidence: 99%

UniProt: the universal protein knowledgebase in 2021

Bateman¹,

Martin²,

Orchard³

et al. 2020

Nucleic Acids Research

Self Cite

5,492

3,195

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“…42 Then prenylated proteins enriched in APP/PS1 mice were mapped along with proteins in the previously curated AD network by Brueza et al . 41 on the mouse PPI network. A subnetwork was constructed by selecting AD network proteins with known direct or indirect interactions with the enriched prenylated proteins.…”

Section: Methodsmentioning

confidence: 99%

“…5A). To investigate how these enriched prenylated proteins may be involved in AD pathogenesis, a protein-protein interaction network of these proteins and known AD network proteins 41,42 was constructed (Fig. 5B).…”

Section: Enrichment and Protein-protein Interaction Analyses Revealed...mentioning

confidence: 99%

“…The protein-protein interaction (PPI) network was constructed using the Biological General Repository for Interaction Datasets (BioGRID) in Cytoscape software (version 3.2.1). 42 Then prenylated proteins enriched in APP/PS1 mice were mapped along with proteins in the previously curated AD network by Brueza et al 41 on the mouse PPI network. A subnetwork was constructed by selecting AD network proteins with known direct or indirect interactions with the enriched prenylated proteins.…”

Section: Gene Ontology and Kegg Pathway Enrichment Analyses And Inter...mentioning

confidence: 99%

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In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

Jeong

Auger

Maity

et al. 2022

Preprint

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Dysregulation of protein prenylation has been implicated in many diseases, including Alzheimer's disease (AD). Prenylomic analysis, the combination of metabolic incorporation of an isoprenoid analogue (C15AlkOPP) into prenylated proteins with a bottom-up proteomic analysis, has allowed identification of prenylated proteins in various cellular models. Here, transgenic AD mice were administered with C15AlkOPP through intracerebroventricular (ICV) infusion over 13 days. Using prenylomic analysis, 36 prenylated proteins were enriched in the brains of AD mice. Importantly, the prenylated forms of 15 proteins were consistently upregulated in AD mice compared to non-transgenic wild-type controls. These results highlight the power of this in vivo metabolic labeling approach to identify multiple post-translationally modified proteins that may serve as potential therapeutic targets for a disease that has proved refractory to treatment thus far. Moreover, this method should be applicable to many other types of protein modifications, significantly broadening its scope.

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“…Figure 1 provides a view of the new IntAct web interface and its functionality, Figure 2 demonstrates the high level of detail provided for a single interaction. In addition to queries, species-specific interactomes (Figure 3 ) and datasets like ‘Alzheimers’ ( 16 ) are available from tiles on the home page.…”

Section: Introductionmentioning

confidence: 99%

The IntAct database: efficient access to fine-grained molecular interaction data

Toro

Shrivastava

Ragueneau

et al. 2021

Nucleic Acids Research

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182

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The IntAct molecular interaction database (https://www.ebi.ac.uk/intact) is a curated resource of molecular interactions, derived from the scientific literature and from direct data depositions. As of August 2021, IntAct provides more than one million binary interactions, curated by twelve global partners of the International Molecular Exchange consortium, for which the IntAct database provides a shared curation and dissemination platform. The IMEx curation policy has always emphasised a fine-grained data and curation model, aiming to capture the relevant experimental detail essential for the interpretation of the provided molecular interaction data. Here, we present recent curation focus and progress, as well as a completely redeveloped website which presents IntAct data in a much more user-friendly and detailed way.

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A Coordinated Approach by Public Domain Bioinformatics Resources to Aid the Fight Against Alzheimer’s Disease Through Expert Curation of Key Protein Targets

Cited by 9 publications

References 76 publications

UniProt: the universal protein knowledgebase in 2021

UniProt: the universal protein knowledgebase in 2021

In vivoprenylomic profiling in the brain of a transgenic mouse model of Alzheimer’s disease reveals increased prenylation of a key set of proteins

The IntAct database: efficient access to fine-grained molecular interaction data

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