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Book ; Online ; E-Book: Computational systems biology approaches in cancer research

Kuperstein, Inna / Barillot, Emmanuel

(Chapman & Hall/CRC mathematical and computational biology)

2020

Author's details	edited by Inna Kuperstein and Emmanuel Barillot
Series title	Chapman & Hall/CRC mathematical and computational biology
Keywords	Systems biology ; Cancer / Research / Methodology ; Computational biology / Methods
Language	English
Size	1 Online-Ressource (xviii, 168 Seiten], Illustrationen
Publisher	CRC Press
Publishing place	Boca Raton, FL
Publishing country	United States
Document type	Book ; Online ; E-Book
Note	"A Chapman & Hall book.". - Includes bibliographical references and index
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
HBZ-ID	HT020334197
ISBN	0-429-33017-0 ; 978-0-429-33017-9 ; 9780367344214 ; 0367344211
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Signalling maps in cancer research: construction and data analysis.

Kondratova, Maria / Sompairac, Nicolas / Barillot, Emmanuel / Zinovyev, Andrei / Kuperstein, Inna

Database : the journal of biological databases and curation

2018 Volume 2018

Abstract: Generation and usage of high-quality molecular signalling network maps can be augmented by standardizing notations, establishing curation workflows and application of computational biology methods to exploit the knowledge contained in the maps. In this ... ...

Abstract	Generation and usage of high-quality molecular signalling network maps can be augmented by standardizing notations, establishing curation workflows and application of computational biology methods to exploit the knowledge contained in the maps. In this manuscript, we summarize the major aims and challenges of assembling information in the form of comprehensive maps of molecular interactions. Mainly, we share our experience gained while creating the Atlas of Cancer Signalling Network. In the step-by-step procedure, we describe the map construction process and suggest solutions for map complexity management by introducing a hierarchical modular map structure. In addition, we describe the NaviCell platform, a computational technology using Google Maps API to explore comprehensive molecular maps similar to geographical maps and explain the advantages of semantic zooming principles for map navigation. We also provide the outline to prepare signalling network maps for navigation using the NaviCell platform. Finally, several examples of cancer high-throughput data analysis and visualization in the context of comprehensive signalling maps are presented.
MeSH term(s)	Animals ; Automatic Data Processing ; Data Curation ; Databases, Genetic ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism ; Signal Transduction
Language	English
Publishing date	2018-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/bay036
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Article ; Online: The Phosphatase PRL-3 Is Involved in Key Steps of Cancer Metastasis.

Duciel, Laura / Monraz Gomez, Luis Cristobal / Kondratova, Maria / Kuperstein, Inna / Saule, Simon

Journal of molecular biology

2019 Volume 431, Issue 17, Page(s) 3056–3067

Abstract: PRL-3 belongs to the PRL phosphatase family. Its physiological role remains unclear, but many studies have identified that PRL-3 is a marker of cancer progression and shown it to be associated with metastasis. Evidence implicating PRL-3 in various ... ...

Abstract	PRL-3 belongs to the PRL phosphatase family. Its physiological role remains unclear, but many studies have identified that PRL-3 is a marker of cancer progression and shown it to be associated with metastasis. Evidence implicating PRL-3 in various elements of the metastatic process, such as the cell cycle, survival, angiogenesis, adhesion, cytoskeleton remodeling, EMT, motility and invasion, has been reported. Furthermore, several molecules acting as direct or indirect substrates have been identified. However, this information was obtained in many different studies, and it remains difficult to see the larger picture. We therefore systematically collected the published information together and used it to develop a comprehensive signaling network map. By analyzing this network map, we were able to retrieve the signaling pathways via which PRL-3 governs the key steps of the metastatic process in cancer. In this review, we summarize current knowledge of the role of PRL-3 in cancer and the molecular mechanisms involved. We also provide the web-based open-source PRL-3 signaling network map, for use in further studies.
MeSH term(s)	Apoptosis ; Carcinogenesis/metabolism ; Cell Adhesion ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cytoskeleton ; Disease Progression ; Humans ; Neoplasm Metastasis ; Neoplasm Proteins/metabolism ; Protein Tyrosine Phosphatases/metabolism ; Signal Transduction ; Systems Biology
Chemical Substances	Neoplasm Proteins ; PTP4A3 protein, human (EC 3.1.3.48) ; Protein Tyrosine Phosphatases (EC 3.1.3.48)
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2019.06.008
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Article ; Online: Network biology elucidates metastatic colon cancer mechanisms.

Kuperstein, Inna / Robine, Sylvie / Zinovyev, Andrei

Cell cycle (Georgetown, Tex.)

2015 Volume 14, Issue 14, Page(s) 2189–2190

MeSH term(s)	Animals ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Epithelial-Mesenchymal Transition ; Humans ; Mice ; Neoplasm Metastasis ; Receptors, Notch/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Receptors, Notch ; Tumor Suppressor Protein p53
Language	English
Publishing date	2015-06-17
Publishing country	United States
Document type	Editorial
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2015.1060816
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Zs.A 5881: Show issues

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Article ; Online: Metabolic and signalling network maps integration: application to cross-talk studies and omics data analysis in cancer.

Sompairac, Nicolas / Modamio, Jennifer / Barillot, Emmanuel / Fleming, Ronan M T / Zinovyev, Andrei / Kuperstein, Inna

BMC bioinformatics

2019 Volume 20, Issue Suppl 4, Page(s) 140

Abstract: Background: The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have ... ...

Abstract	Background: The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by integrating of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease. Results: We combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration ( https://navicell.curie.fr/pages/maps_ReconMap%202.html ). In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated networks ACSN-ReconMap 2.0 are accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated networks were applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified. Conclusions: As knowledge evolves and new omics data becomes more heterogeneous, gathering together existing domains of biology under common platforms is essential. We believe that an integrated ACSN-ReconMap 2.0 networks will help in understanding various disease mechanisms and discovery of new interactions at the intersection of cell signalling and metabolism. In addition, the successful integration of metabolic and signalling networks allows broader systems biology approach application for data interpretation and retrieval of intervention points to tackle simultaneously the key players coordinating signalling and metabolism in human diseases.
MeSH term(s)	Data Analysis ; Female ; Genomics/methods ; Humans ; Metabolic Networks and Pathways ; Neoplasms/genetics ; Signal Transduction ; Software ; Systems Biology
Language	English
Publishing date	2019-04-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/s12859-019-2682-z
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Article ; Online: NaviCom: a web application to create interactive molecular network portraits using multi-level omics data.

Dorel, Mathurin / Viara, Eric / Barillot, Emmanuel / Zinovyev, Andrei / Kuperstein, Inna

Database : the journal of biological databases and curation

2017 Volume 2017, Issue 1

Abstract: Human diseases such as cancer are routinely characterized by high-throughput molecular technologies, and multi-level omics data are accumulated in public databases at increasing rate. Retrieval and visualization of these data in the context of molecular ... ...

Abstract	Human diseases such as cancer are routinely characterized by high-throughput molecular technologies, and multi-level omics data are accumulated in public databases at increasing rate. Retrieval and visualization of these data in the context of molecular network maps can provide insights into the pattern of regulation of molecular functions reflected by an omics profile. In order to make this task easy, we developed NaviCom, a Python package and web platform for visualization of multi-level omics data on top of biological network maps. NaviCom is bridging the gap between cBioPortal, the most used resource of large-scale cancer omics data and NaviCell, a data visualization web service that contains several molecular network map collections. NaviCom proposes several standardized modes of data display on top of molecular network maps, allowing addressing specific biological questions. We illustrate how users can easily create interactive network-based cancer molecular portraits via NaviCom web interface using the maps of Atlas of Cancer Signalling Network (ACSN) and other maps. Analysis of these molecular portraits can help in formulating a scientific hypothesis on the molecular mechanisms deregulated in the studied disease. Database url : NaviCom is available at https://navicom.curie.fr.
MeSH term(s)	Computational Biology ; Humans ; Internet ; Neoplasms/metabolism
Language	English
Publishing date	2017-01-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/bax026
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Article: Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases.

Ravel, Jean-Marie / Monraz Gomez, L Cristobal / Sompairac, Nicolas / Calzone, Laurence / Zhivotovsky, Boris / Kroemer, Guido / Barillot, Emmanuel / Zinovyev, Andrei / Kuperstein, Inna

Cancers

2020 Volume 12, Issue 4

Abstract: The processes leading to, or avoiding cell death are widely studied, because of their frequent perturbation in various diseases. Cell death occurs in three highly interconnected steps: Initiation, signaling and execution. We used a systems biology ... ...

Abstract	The processes leading to, or avoiding cell death are widely studied, because of their frequent perturbation in various diseases. Cell death occurs in three highly interconnected steps: Initiation, signaling and execution. We used a systems biology approach to gather information about all known modes of regulated cell death (RCD). Based on the experimental data retrieved from literature by manual curation, we graphically depicted the biological processes involved in RCD in the form of a seamless comprehensive signaling network map. The molecular mechanisms of each RCD mode are represented in detail. The RCD network map is divided into 26 functional modules that can be visualized contextually in the whole seamless network, as well as in individual diagrams. The resource is freely available and accessible via several web platforms for map navigation, data integration, and analysis. The RCD network map was employed for interpreting the functional differences in cell death regulation between Alzheimer's disease and non-small cell lung cancer based on gene expression data that allowed emphasizing the molecular mechanisms underlying the inverse comorbidity between the two pathologies. In addition, the map was used for the analysis of genomic and transcriptomic data from ovarian cancer patients that provided RCD map-based signatures of four distinct tumor subtypes and highlighted the difference in regulations of cell death molecular mechanisms.
Language	English
Publishing date	2020-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12040990
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Article ; Online: Network-based approaches for drug response prediction and targeted therapy development in cancer.

Dorel, Mathurin / Barillot, Emmanuel / Zinovyev, Andrei / Kuperstein, Inna

Biochemical and biophysical research communications

2015 Volume 464, Issue 2, Page(s) 386–391

Abstract: Signaling pathways implicated in cancer create a complex network with numerous regulatory loops and redundant pathways. This complexity explains frequent failure of one-drug-one-target paradigm of treatment, resulting in drug resistance in patients. To ... ...

Abstract	Signaling pathways implicated in cancer create a complex network with numerous regulatory loops and redundant pathways. This complexity explains frequent failure of one-drug-one-target paradigm of treatment, resulting in drug resistance in patients. To overcome the robustness of cell signaling network, cancer treatment should be extended to a combination therapy approach. Integrating and analyzing patient high-throughput data together with the information about biological signaling machinery may help deciphering molecular patterns specific to each patient and finding the best combinations of candidates for therapeutic targeting. We review state of the art in the field of targeted cancer medicine from the computational systems biology perspective. We summarize major signaling network resources and describe their characteristics with respect to applicability for drug response prediction and intervention targets suggestion. Thus discuss methods for prediction of drug sensitivity and intervention combinations using signaling networks together with high-throughput data. Gradual integration of these approaches into clinical routine will improve prediction of response to standard treatments and adjustment of intervention schemes.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Models, Theoretical ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Signal Transduction
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2015-08-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2015.06.094
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Article ; Online: Application of Atlas of Cancer Signalling Network in preclinical studies.

Monraz Gomez, L Cristobal / Kondratova, Maria / Ravel, Jean-Marie / Barillot, Emmanuel / Zinovyev, Andrei / Kuperstein, Inna

Briefings in bioinformatics

2018 Volume 20, Issue 2, Page(s) 701–716

Abstract: Cancer initiation and progression are associated with multiple molecular mechanisms. The knowledge of these mechanisms is expanding and should be converted into guidelines for tackling the disease. Here, we discuss the formalization of biological ... ...

Abstract	Cancer initiation and progression are associated with multiple molecular mechanisms. The knowledge of these mechanisms is expanding and should be converted into guidelines for tackling the disease. Here, we discuss the formalization of biological knowledge into a comprehensive resource: the Atlas of Cancer Signalling Network (ACSN) and the Google Maps-based tool NaviCell, which supports map navigation. The application of ACSN for omics data visualization, in the context of signalling maps, is possible via the NaviCell Web Service module and through the NaviCom tool. It allows generation of network-based molecular portraits of cancer using multilevel omics data. We review how these resources and tools are applied for cancer preclinical studies. Structural analysis of the maps together with omics data helps to rationalize the synergistic effects of drugs and allows design of complex disease stage-specific druggable interventions. The use of ACSN modules and maps as signatures of biological functions can help in cancer data analysis and interpretation. In addition, they empowered finding of associations between perturbations in particular molecular mechanisms and the risk to develop a specific type of cancer. These approaches are helpful, among others, to study the interplay between molecular mechanisms of cancer. It opens an opportunity to decipher how gene interactions govern the hallmarks of cancer in specific contexts. We discuss a perspective to develop a flexible methodology and a pipeline to enable systematic omics data analysis in the context of signalling network maps, for stratifying patients and suggesting interventions points and drug repositioning in cancer and other diseases.
MeSH term(s)	Atlases as Topic ; Computational Biology/methods ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism ; Signal Transduction
Language	English
Publishing date	2018-04-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2068142-2
ISSN	1477-4054 ; 1467-5463
ISSN (online)	1477-4054
ISSN	1467-5463
DOI	10.1093/bib/bby031
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Article ; Online: Metabolic and signalling network maps integration

Nicolas Sompairac / Jennifer Modamio / Emmanuel Barillot / Ronan M. T. Fleming / Andrei Zinovyev / Inna Kuperstein

BMC Bioinformatics, Vol 20, Iss S4, Pp 1-

application to cross-talk studies and omics data analysis in cancer

2019 Volume 14

Abstract: Abstract Background The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they ... ...

Abstract	Abstract Background The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by integrating of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease. Results We combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration (https://navicell.curie.fr/pages/maps_ReconMap%202.html). In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated networks ACSN-ReconMap 2.0 are accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated networks were applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified. Conclusions As knowledge evolves ...
Keywords	Signalling ; Metabolism ; Networks ; Comprehensive map ; Systems biology ; Cancer ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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