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  1. AU="Kutmon, M."
  2. AU="Christofoletti, Ronaldo Adriano"
  3. AU="Greice Machado Pieszak"

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  1. Artikel ; Online: Tissue-specific pathway activities: A retrospective analysis in COVID-19 patients.

    Pham, Nhung / Hu, Finterly / Evelo, Chris T / Kutmon, Martina

    Frontiers in immunology

    2022  Band 13, Seite(n) 963357

    Abstract: The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects ... ...

    Abstract The ACE2 receptors essential for SARS-CoV-2 infections are expressed not only in the lung but also in many other tissues in the human body. To better understand the disease mechanisms and progression, it is essential to understand how the virus affects and alters molecular pathways in the different affected tissues. In this study, we mapped the proteomics data obtained from Nie X.
    Mesh-Begriff(e) Angiotensin-Converting Enzyme 2 ; Anticoagulants ; Arachidonic Acid ; Bradykinin/metabolism ; COVID-19 ; Humans ; Kallikreins/metabolism ; Male ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System ; Retrospective Studies ; SARS-CoV-2 ; alpha-Linolenic Acid
    Chemische Substanzen Anticoagulants ; alpha-Linolenic Acid (0RBV727H71) ; Arachidonic Acid (27YG812J1I) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Kallikreins (EC 3.4.21.-) ; Bradykinin (S8TIM42R2W)
    Sprache Englisch
    Erscheinungsdatum 2022-09-15
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.963357
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Exploring pathway interactions to detect molecular mechanisms of disease: 22q11.2 deletion syndrome.

    Shin, Woosub / Kutmon, Martina / Mina, Eleni / van Amelsvoort, Therese / Evelo, Chris T / Ehrhart, Friederike

    Orphanet journal of rare diseases

    2023  Band 18, Heft 1, Seite(n) 335

    Abstract: Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, ... ...

    Abstract Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic disorder characterized by the deletion of adjacent genes at a location specified as q11.2 of chromosome 22, resulting in an array of clinical phenotypes including autistic spectrum disorder, schizophrenia, congenital heart defects, and immune deficiency. Many characteristics of the disorder are known, such as the phenotypic variability of the disease and the biological processes associated with it; however, the exact and systemic molecular mechanisms between the deleted area and its resulting clinical phenotypic expression, for example that of neuropsychiatric diseases, are not yet fully understood.
    Results: Using previously published transcriptomics data (GEO:GSE59216), we constructed two datasets: one set compares 22q11DS patients experiencing neuropsychiatric diseases versus healthy controls, and the other set 22q11DS patients without neuropsychiatric diseases versus healthy controls. We modified and applied the pathway interaction method, originally proposed by Kelder et al. (2011), on a network created using the WikiPathways pathway repository and the STRING protein-protein interaction database. We identified genes and biological processes that were exclusively associated with the development of neuropsychiatric diseases among the 22q11DS patients. Compared with the 22q11DS patients without neuropsychiatric diseases, patients experiencing neuropsychiatric diseases showed significant overrepresentation of regulated genes involving the natural killer cell function and the PI3K/Akt signalling pathway, with affected genes being closely associated with downregulation of CRK like proto-oncogene adaptor protein. Both the pathway interaction and the pathway overrepresentation analysis observed the disruption of the same biological processes, even though the exact lists of genes collected by the two methods were different.
    Conclusions: Using the pathway interaction method, we were able to detect a molecular network that could possibly explain the development of neuropsychiatric diseases among the 22q11DS patients. This way, our method was able to complement the pathway overrepresentation analysis, by filling the knowledge gaps on how the affected pathways are linked to the original deletion on chromosome 22. We expect our pathway interaction method could be used for problems with similar contexts, where complex genetic mechanisms need to be identified to explain the resulting phenotypic plasticity.
    Mesh-Begriff(e) Humans ; DiGeorge Syndrome/genetics ; Phosphatidylinositol 3-Kinases ; Phenotype ; Gene Expression Profiling ; Heart Defects, Congenital
    Chemische Substanzen Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Sprache Englisch
    Erscheinungsdatum 2023-10-24
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2225857-7
    ISSN 1750-1172 ; 1750-1172
    ISSN (online) 1750-1172
    ISSN 1750-1172
    DOI 10.1186/s13023-023-02953-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Buch ; Online: BridgeDb

    Kutmon, Martina / Willighagen, Egon

    Human and SARS-related corona virus gene/protein mapping database derived from Wikidata

    2020  

    Abstract: Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq and UniProt are provided in the .bridge file. 65 Wikidata (Wd) identifiers 65 NCBI Gene (L) identifiers 42 RefSeq ( ...

    Abstract Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq and UniProt are provided in the .bridge file. 65 Wikidata (Wd) identifiers 65 NCBI Gene (L) identifiers 42 RefSeq (Q) identifiers 39 UniProt (S) identifiers

    License: Creative Commons CC0
    Schlagwörter BridgeDb ; identifier mapping ; coronavirus ; covid19
    Erscheinungsdatum 2020-04-01
    Erscheinungsland eu
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Buch ; Online: BridgeDb

    Kutmon, Martina / Willighagen, Egon

    Human and SARS-related corona virus gene/protein mapping database derived from Wikidata

    2020  

    Abstract: Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq, UniProt and Guide to Pharmacology Target are provided in the .bridge file. 170 Wikidata (Wd) identifiers 70 NCBI ... ...

    Abstract Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq, UniProt and Guide to Pharmacology Target are provided in the .bridge file. 170 Wikidata (Wd) identifiers 70 NCBI Gene (L) identifiers 58 RefSeq (Q) identifiers 60 UniProt (S) identifiers 10 Guide to Pharmacology Target (Gpt) identifiers Virus name was added as attribute ("virus") to Wikidata Xrefs.

    License: Creative Commons CC0
    Schlagwörter BridgeDb ; identifier mapping ; coronavirus ; covid19
    Erscheinungsdatum 2020-05-27
    Erscheinungsland eu
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Buch ; Online: BridgeDb

    Kutmon, Martina / Willighagen, Egon

    Human and SARS-related corona virus gene/protein mapping database derived from Wikidata

    2020  

    Abstract: Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq and UniProt are provided in the .bridge file. 163 Wikidata (Wd) identifiers 69 NCBI Gene (L) identifiers 55 RefSeq ...

    Abstract Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq and UniProt are provided in the .bridge file. 163 Wikidata (Wd) identifiers 69 NCBI Gene (L) identifiers 55 RefSeq (Q) identifiers 59 UniProt (S) identifiers Virus name was added as attribute ("virus") to Wikidata Xrefs.

    License: Creative Commons CC0
    Schlagwörter BridgeDb ; identifier mapping ; coronavirus ; covid19
    Erscheinungsdatum 2020-04-14
    Erscheinungsland eu
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Buch ; Online: BridgeDb

    Kutmon, Martina / Willighagen, Egon

    Human and SARS-related corona virus gene/protein mapping database derived from Wikidata

    2020  

    Abstract: Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq, UniProt and Guide to Pharmacology Target are provided in the .bridge file. 169 Wikidata (Wd) identifiers 70 NCBI ... ...

    Abstract Gene/Protein mappings for human and SARS-related corona viruses. Data is derived from Wikidata. Mappings from Wikidata to NCBI Gene, RefSeq, UniProt and Guide to Pharmacology Target are provided in the .bridge file. 169 Wikidata (Wd) identifiers 70 NCBI Gene (L) identifiers 58 RefSeq (Q) identifiers 59 UniProt (S) identifiers 10 Guide to Pharmacology Target (Gpt) identifiers Virus name was added as attribute ("virus") to Wikidata Xrefs.

    License: Creative Commons CC0
    Schlagwörter BridgeDb ; identifier mapping ; coronavirus ; covid19
    Erscheinungsdatum 2020-05-20
    Erscheinungsland eu
    Dokumenttyp Buch ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Investigating the Molecular Processes behind the Cell-Specific Toxicity Response to Titanium Dioxide Nanobelts.

    Winckers, Laurent A / Evelo, Chris T / Willighagen, Egon L / Kutmon, Martina

    International journal of molecular sciences

    2021  Band 22, Heft 17

    Abstract: Some engineered nanomaterials incite toxicological effects, but the underlying molecular processes are understudied. The varied physicochemical properties cause different initial molecular interactions, complicating toxicological predictions. Gene ... ...

    Abstract Some engineered nanomaterials incite toxicological effects, but the underlying molecular processes are understudied. The varied physicochemical properties cause different initial molecular interactions, complicating toxicological predictions. Gene expression data allow us to study the responses of genes and biological processes. Overrepresentation analysis identifies enriched biological processes using the experimental data but prompts broad results instead of detailed toxicological processes. We demonstrate a targeted filtering approach to compare public gene expression data for low and high exposure on three cell lines to titanium dioxide nanobelts. Our workflow finds cell and concentration-specific changes in affected pathways linked to four Gene Ontology terms (apoptosis, inflammation, DNA damage, and oxidative stress) to select pathways with a clear toxicity focus. We saw more differentially expressed genes at higher exposure, but our analysis identifies clear differences between the cell lines in affected processes. Colorectal adenocarcinoma cells showed resilience to both concentrations. Small airway epithelial cells displayed a cytotoxic response to the high concentration, but not as strongly as monocytic-like cells. The pathway-gene networks highlighted the gene overlap between altered toxicity-related pathways. The automated workflow is flexible and can focus on other biological processes by selecting other GO terms.
    Mesh-Begriff(e) Adenocarcinoma/drug therapy ; Adenocarcinoma/pathology ; Cells, Cultured ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; DNA Damage ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Humans ; Monocytes/drug effects ; Monocytes/pathology ; Nanoparticles/administration & dosage ; Nanoparticles/toxicity ; Oxidative Stress ; Titanium/toxicity
    Chemische Substanzen titanium dioxide (15FIX9V2JP) ; Titanium (D1JT611TNE)
    Sprache Englisch
    Erscheinungsdatum 2021-08-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22179432
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions.

    Miller, Ryan A / Kutmon, Martina / Bohler, Anwesha / Waagmeester, Andra / Evelo, Chris T / Willighagen, Egon L

    PloS one

    2022  Band 17, Heft 4, Seite(n) e0263057

    Abstract: To grasp the complexity of biological processes, the biological knowledge is often translated into schematic diagrams of, for example, signalling and metabolic pathways. These pathway diagrams describe relevant connections between biological entities and ...

    Abstract To grasp the complexity of biological processes, the biological knowledge is often translated into schematic diagrams of, for example, signalling and metabolic pathways. These pathway diagrams describe relevant connections between biological entities and incorporate domain knowledge in a visual format making it easier for humans to interpret. Still, these diagrams can be represented in machine readable formats, as done in the KEGG, Reactome, and WikiPathways databases. However, while humans are good at interpreting the message of the creators of diagrams, algorithms struggle when the diversity in drawing approaches increases. WikiPathways supports multiple drawing styles which need harmonizing to offer semantically enriched access. Particularly challenging, here, are the interactions between the biological entities that underlie the biological causality. These interactions provide information about the biological process (metabolic conversion, inhibition, etc.), the direction, and the participating entities. Availability of the interactions in a semantic and harmonized format is essential for searching the full network of biological interactions. We here study how the graphically-modelled biological knowledge in diagrams can be semantified and harmonized, and exemplify how the resulting data is used to programmatically answer biological questions. We find that we can translate graphically modelled knowledge to a sufficient degree into a semantic model and discuss some of the current limitations. We then use this to show that reproducible notebooks can be used to explore up- and downstream targets of MECP2 and to analyse the sphingolipid metabolism. Our results demonstrate that most of the graphical biological knowledge from WikiPathways is modelled into the semantic layer with the semantic information intact and connectivity information preserved. Being able to evaluate how biological elements affect each other is useful and allows, for example, the identification of up or downstream targets that will have a similar effect when modified.
    Mesh-Begriff(e) Algorithms ; Biological Phenomena ; Databases, Factual ; Humans ; Metabolic Networks and Pathways ; Signal Transduction/physiology
    Sprache Englisch
    Erscheinungsdatum 2022-04-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0263057
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Elucidating the Corneal Endothelial Cell Proliferation Capacity through an Interspecies Transcriptome Comparison.

    Català, Pere / Vivensang, Flora / van Beek, Daan / Adriaens, Michiel E / Dickman, Mor M / LaPointe, Vanessa L S / Kutmon, Martina

    Advanced biology

    2023  Band 7, Heft 10, Seite(n) e2300065

    Abstract: The regenerative capacity of corneal endothelial cells (CECs) differs between species; in bigger mammals, CECs are arrested in a non-proliferative state. Damage to these cells can compromise their function causing corneal opacity. Corneal transplantation ...

    Abstract The regenerative capacity of corneal endothelial cells (CECs) differs between species; in bigger mammals, CECs are arrested in a non-proliferative state. Damage to these cells can compromise their function causing corneal opacity. Corneal transplantation is the current treatment for the recovery of clear eyesight, but the donor tissue demand is higher than the availability and there is a need to develop novel treatments. Interestingly, rabbit CECs retain a high proliferative profile and can repopulate the endothelium. There is a lack of fundamental knowledge to explain these differences. Gaining information on their transcriptomic variances could allow the identification of CEC proliferation drivers. In this study, human, sheep, and rabbit CECs are analyzed at the transcriptomic level. To understand the differences across each species, a pipeline for the analysis of pathways with different activities is generated. The results reveal that 52 pathways have different activity when comparing species with non-proliferative CECs (human and sheep) to species with proliferative CECs (rabbit). The results show that Notch and TGF-β pathways have increased activity in species with non-proliferative CECs, which might be associated with their low proliferation. Overall, this study illustrates transcriptomic pathway-level differences that can provide leads to develop novel therapies to regenerate the corneal endothelium.
    Sprache Englisch
    Erscheinungsdatum 2023-04-16
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ISSN 2701-0198
    ISSN (online) 2701-0198
    DOI 10.1002/adbi.202300065
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

    Pham, Nhung / Talih, Nuray / Ehrhart, Friederike / Evelo, Chris / Kutmon, Martina

    bioRxiv

    Abstract: Early and persistent defects in B cell subsets such as memory B cells were shown to be correlated with poor outcomes in COVID-19 patients. This research aimed to develop a molecular pathway model to understand the B cell development in COVID-19. A B cell ...

    Abstract Early and persistent defects in B cell subsets such as memory B cells were shown to be correlated with poor outcomes in COVID-19 patients. This research aimed to develop a molecular pathway model to understand the B cell development in COVID-19. A B cell transcriptomics dataset, obtained from COVID-19 patients, was analyzed on the resulting pathway model to study B cell activation. The pathway showed two distinct gene expression profiles between asymptomatic and symptomatic patients. In asymptomatic patients, there is an increase in transcript levels of antiviral interferon-stimulated genes such as ISG15, IFITM1, and NEAT1 and a driving gene for the extrafollicular pathway CXCR4 indicating a formation of plasmablast. In symptomatic patients, the results suggest an inhibition occurring at the germinal center hinting at a reduction in memory B cell production. Transcripts of driver gene CXCR5 involved in germinal center development is one of the most downregulated genes. This could contribute to the shortage in the formation of memory B cells in COVID-19. Concluding, in SARS-CoV-2 infection, B cells follow different activation routes in asymptomatic and symptomatic patients. In this study, we constructed a pathway that allowed us to analyze and interpret activation patterns of B cells in COVID-19 patients and their link to disease severity. Importantly, the pathway and approach can be reused for further research in COVID-19 or other diseases.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2022-12-20
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2022.12.19.521064
    Datenquelle COVID19

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