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  1. Article: Assembling Disease Networks From Causal Interaction Resources.

    Cesareni, Gianni / Sacco, Francesca / Perfetto, Livia

    Frontiers in genetics

    2021  Volume 12, Page(s) 694468

    Abstract: The development of high-throughput high-content technologies and the increased ease in their application in clinical settings has raised the expectation of an important impact of these technologies on diagnosis and personalized therapy. Patient genomic ... ...

    Abstract The development of high-throughput high-content technologies and the increased ease in their application in clinical settings has raised the expectation of an important impact of these technologies on diagnosis and personalized therapy. Patient genomic and expression profiles yield lists of genes that are mutated or whose expression is modulated in specific disease conditions. The challenge remains of extracting from these lists functional information that may help to shed light on the mechanisms that are perturbed in the disease, thus setting a rational framework that may help clinical decisions. Network approaches are playing an increasing role in the organization and interpretation of patients' data. Biological networks are generated by connecting genes or gene products according to experimental evidence that demonstrates their interactions. Till recently most approaches have relied on networks based on physical interactions between proteins. Such networks miss an important piece of information as they lack details on the functional consequences of the interactions. Over the past few years, a number of resources have started collecting causal information of the type protein A activates/inactivates protein B, in a structured format. This information may be represented as signed directed graphs where physiological and pathological signaling can be conveniently inspected. In this review we will (i) present and compare these resources and discuss the different scope in comparison with pathway resources; (ii) compare resources that explicitly capture causality in terms of data content and proteome coverage (iii) review how causal-graphs can be used to extract disease-specific Boolean networks.
    Language English
    Publishing date 2021-06-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.694468
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: SIGNORApp: a Cytoscape 3 application to access SIGNOR data.

    De Marinis, Ilaria / Lo Surdo, Prisca / Cesareni, Gianni / Perfetto, Livia

    Bioinformatics (Oxford, England)

    2021  Volume 38, Issue 6, Page(s) 1764–1766

    Abstract: Summary: SIGNORApp is a Cytoscape 3 (3.8 and later) application that provides access to causal interactions annotated in the SIGNOR resource. The application builds networks that can be represented as weighted, signed, directed graphs, where nodes are ... ...

    Abstract Summary: SIGNORApp is a Cytoscape 3 (3.8 and later) application that provides access to causal interactions annotated in the SIGNOR resource. The application builds networks that can be represented as weighted, signed, directed graphs, where nodes are interacting biological entities and edges represent causal interactions captured by expert curators from experiments reported in peer reviewed journals. Users can query the SIGNOR dataset with (i) single or multiple entity name(s) or identifier(s) and optionally they may require to include in the output network their interacting partners, (ii) browse pathways that are annotated in the SIGNOR resource and (iii) extract the entire causal interactome. The app offers two visualizations modes: one only displaying entity interactions and a second emphasizing the post-translational modifications occurring as a consequence of the interaction. In addition, users can click on nodes and edges to access entity and interaction annotations. Causal information is available for three model organisms: Homo sapiens, Mus musculus and Rattus norvegicus.
    Availability and implementation: SIGNORApp has been developed for Cytoscape 3 (3.8 and later) in the Java programming language. The latest source code and the plugin can be found at: https://github.com/SIGNORcysAPP/signor-app and https://apps.cytoscape.org/apps/signorapp, respectively.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Mice ; Humans ; Animals ; Rats ; Software ; Protein Processing, Post-Translational
    Language English
    Publishing date 2021-12-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btab865
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A Resource to Infer Molecular Paths Linking Cancer Mutations to Perturbation of Cell Metabolism.

    Iannuccelli, Marta / Lo Surdo, Prisca / Licata, Luana / Castagnoli, Luisa / Cesareni, Gianni / Perfetto, Livia

    Frontiers in molecular biosciences

    2022  Volume 9, Page(s) 893256

    Abstract: Some inherited or somatically-acquired gene variants are observed significantly more frequently in the genome of cancer cells. Although many of these cannot be confidently classified as driver mutations, they may contribute to shaping a cell environment ... ...

    Abstract Some inherited or somatically-acquired gene variants are observed significantly more frequently in the genome of cancer cells. Although many of these cannot be confidently classified as driver mutations, they may contribute to shaping a cell environment that favours cancer onset and development. Understanding how these gene variants causally affect cancer phenotypes may help developing strategies for reverting the disease phenotype. Here we focus on variants of genes whose products have the potential to modulate metabolism to support uncontrolled cell growth. Over recent months our team of expert curators has undertaken an effort to annotate in the database SIGNOR 1) metabolic pathways that are deregulated in cancer and 2) interactions connecting oncogenes and tumour suppressors to metabolic enzymes. In addition, we refined a recently developed graph analysis tool that permits users to infer causal paths leading from any human gene to modulation of metabolic pathways. The tool grounds on a human signed and directed network that connects ∼8400 biological entities such as proteins and protein complexes via causal relationships. The network, which is based on more than 30,000 published causal links, can be downloaded from the SIGNOR website. In addition, as SIGNOR stores information on drugs or other chemicals targeting the activity of many of the genes in the network, the identification of likely functional paths offers a rational framework for exploring new therapeutic strategies that revert the disease phenotype.
    Language English
    Publishing date 2022-05-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2022.893256
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SPV: a JavaScript Signaling Pathway Visualizer.

    Calderone, Alberto / Cesareni, Gianni

    Bioinformatics (Oxford, England)

    2017  Volume 34, Issue 15, Page(s) 2684–2686

    Abstract: Summary: The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free ... ...

    Abstract Summary: The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. Signaling Pathway Visualizer is a free open source JavaScript library, which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks.
    Availability and implementation: Freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js.
    MeSH term(s) Computational Biology/methods ; Protein Interaction Maps ; Signal Transduction ; Software
    Language English
    Publishing date 2017-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/bty188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Correction: Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders.

    Iannuccelli, Marta / Vitriolo, Alessandro / Licata, Luana / Lo Surdo, Prisca / Contino, Silvia / Cheroni, Cristina / Capocefalo, Daniele / Castagnoli, Luisa / Testa, Giuseppe / Cesareni, Gianni / Perfetto, Livia

    Molecular psychiatry

    2024  

    Language English
    Publishing date 2024-01-24
    Publishing country England
    Document type Published Erratum
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-024-02432-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Spotlight on... Gianni Cesareni. An interview by Daniela Ruffell .

    Cesareni, Gianni

    FEBS letters

    2008  Volume 582, Issue 9, Page(s) 1291–1292

    MeSH term(s) Genetics ; History, 21st Century ; Italy ; Publishing
    Language English
    Publishing date 2008-04-16
    Publishing country England
    Document type Biography ; Historical Article ; Interview
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1016/j.febslet.2008.03.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: Analysis of Triplet Motifs in Biological Signed Oriented Graphs Suggests a Relationship Between Fine Topology and Function

    Calderone, Alberto / Cesareni, Gianni

    2018  

    Abstract: Background: Networks in different domains are characterized by similar global characteristics while differing in local structures. To further extend this concept, we investigated network regularities on a fine scale in order to examine the functional ... ...

    Abstract Background: Networks in different domains are characterized by similar global characteristics while differing in local structures. To further extend this concept, we investigated network regularities on a fine scale in order to examine the functional impact of recurring motifs in signed oriented biological networks. In this work we generalize to signaling net works some considerations made on feedback and feed forward loops and extend them by adding a close scrutiny of Linear Triplets, which have not yet been investigate in detail. Results: We studied the role of triplets, either open or closed (Loops or linear events) by enumerating them in different biological signaling networks and by comparing their significance profiles. We compared different data sources and investigated the fine topology of protein networks representing causal relationships based on transcriptional control, phosphorylation, ubiquitination and binding. Not only were we able to generalize findings that have already been reported but we also highlighted a connection between relative motif abundance and node function. Furthermore, by analyzing for the first time Linear Triplets, we highlighted the relative importance of nodes sitting in specific positions in closed signaling triplets. Finally, we tried to apply machine learning to show that a combination of motifs features can be used to derive node function. Availability: The triplets counter used for this work is available as a Cytoscape App and as a standalone command line Java application. http://apps.cytoscape.org/apps/counttriplets Keywords: Graph theory, graph analysis, graph topology, machine learning, cytoscape
    Keywords Quantitative Biology - Molecular Networks ; Computer Science - Machine Learning ; 05C10 ; 05C30
    Subject code 006
    Publishing date 2018-03-17
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: SPV: a JavaScript Signaling Pathway Visualizer

    Calderone, Alberto / Cesareni, Gianni / Stegle, Oliver

    Bioinformatics. 2018 Aug. 01, v. 34, no. 15

    2018  

    Abstract: The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, ... ...

    Abstract The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. Signaling Pathway Visualizer is a free open source JavaScript library, which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein–protein interaction networks. Freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js.
    Keywords bioinformatics ; computer software ; protein-protein interactions ; signal transduction ; world wide web
    Language English
    Dates of publication 2018-0801
    Size p. 2684-2686.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 1468345-3
    ISSN 1460-2059 ; 1367-4811 ; 1367-4803
    ISSN (online) 1460-2059 ; 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/bty188
    Database NAL-Catalogue (AGRICOLA)

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  9. Article: Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines.

    Riccio, Federica / Micarelli, Elisa / Secci, Riccardo / Giuliani, Giulio / Vumbaca, Simone / Massacci, Giorgia / Castagnoli, Luisa / Fuoco, Claudia / Cesareni, Gianni

    Cell death discovery

    2022  Volume 8, Issue 1, Page(s) 16

    Abstract: Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used ... ...

    Abstract Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used data from the Connectivity Map (CMap) to produce a ranked list of drugs according to their potential to activate transcription factors that mediate myeloid differentiation of leukemic progenitor cells. To validate our strategy, we tested the in vitro differentiation potential of candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, which were ranked high in the inferred list, were confirmed to promote significant differentiation of HL-60. These compounds may be considered candidate for differentiation therapy. The method that we have developed is versatile and it can be adapted to different drug repurposing projects.
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-021-00811-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: SIGNOR 3.0, the SIGnaling network open resource 3.0: 2022 update.

    Lo Surdo, Prisca / Iannuccelli, Marta / Contino, Silvia / Castagnoli, Luisa / Licata, Luana / Cesareni, Gianni / Perfetto, Livia

    Nucleic acids research

    2022  Volume 51, Issue D1, Page(s) D631–D637

    Abstract: The SIGnaling Network Open Resource (SIGNOR 3.0, https://signor.uniroma2.it) is a public repository that captures causal information and represents it according to an 'activity-flow' model. SIGNOR provides freely-accessible static maps of causal ... ...

    Abstract The SIGnaling Network Open Resource (SIGNOR 3.0, https://signor.uniroma2.it) is a public repository that captures causal information and represents it according to an 'activity-flow' model. SIGNOR provides freely-accessible static maps of causal interactions that can be tailored, pruned and refined to build dynamic and predictive models. Each signaling relationship is annotated with an effect (up/down-regulation) and with the mechanism (e.g. binding, phosphorylation, transcriptional activation, etc.) causing the regulation of the target entity. Since its latest release, SIGNOR has undergone a significant upgrade including: (i) a new website that offers an improved user experience and novel advanced search and graph tools; (ii) a significant content growth adding up to a total of approx. 33,000 manually-annotated causal relationships between more than 8900 biological entities; (iii) an increase in the number of manually annotated pathways, currently including pathways deregulated by SARS-CoV-2 infection or involved in neurodevelopment synaptic transmission and metabolism, among others; (iv) additional features such as new model to represent metabolic reactions and a new confidence score assigned to each interaction.
    MeSH term(s) Humans ; COVID-19 ; Phosphorylation ; SARS-CoV-2/genetics ; Signal Transduction ; Databases, Protein ; Gene Expression Regulation
    Language English
    Publishing date 2022-10-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkac883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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