An in silico-based approach to improve the efficacy and precision of drug REPurpOsing TRIALs for a mechanism-based patient cohort with predominant cerebro-cardiovascular phenotypes

Project Information

REPO-TRIAL

Grant agreement ID: 777111

DOI 10.3030/777111

Project closed

EC signature date 31 October 2017

Start date 1 February 2018

End date 31 January 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost € 5 536 775,64

EU contribution € 5 536 772,50

Coordinated by

UNIVERSITEIT MAASTRICHT
Netherlands

Deliverables

Websites, patent fillings, videos etc. (3)

Publish an open pre-clinical biobank for pre-clinical animal models related commROCG and other disease phenotypes for both genders

Publish an open preclinical biobank for preclinical animal models related commROCG and other disease phenotypes for both genders

Project brochure and professional templates
Communication and dissemination plan

Other (3)

Software for detection of pathway co-enrichment for extracting of patient(group)-specific pathways also enriched in target sites of effective drugs
Drugome 1.0 network

Drugome 10 network

Diseasome 2.0 network

Publications

Peer reviewed articles (21)

Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease

Author(s): Vu Thao-Vi Dao, Mahmoud H. Elbatreek, Martin Deile, Pavel I. Nedvetsky, Andreas Güldner, César Ibarra-Alvarado, Axel Gödecke, Harald H. H. W. Schmidt
Published in: Scientific Reports, Issue 10/1, 2020, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-020-66639-w

On the Clinical Pharmacology of Reactive Oxygen Species

Author(s): Ana I. Casas, Cristian Nogales, Hermann A. M. Mucke, Alexandra Petraina, Antonio Cuadrado, Ana I. Rojo, Pietro Ghezzi, Vincent Jaquet, Fiona Augsburger, Francois Dufrasne, Jalal Soubhye, Soni Deshwal, Moises Di Sante, Nina Kaludercic, Fabio Di Lisa, Harald H. H. W. Schmidt
Published in: Pharmacological Reviews, Issue 72/4, 2020, Page(s) 801-828, ISSN 0031-6997
Publisher: American Society for Pharmacology and Experimental Therapeutics
DOI: 10.1124/pr.120.019422

De Novo and Supervised Endophenotyping Using Network-Guided Ensemble Learning

Author(s): Simon J. Larsen, Harald H.H.W. Schmidt, Jan Baumbach
Published in: Systems Medicine, Issue 3/1, 2020, Page(s) 8-21, ISSN 2573-3370
Publisher: Network and Systems Medicine
DOI: 10.1089/sysm.2019.0008

Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology

Author(s): Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F Lüscher, Rodolphe Fischmeister, David A Kass, John C Burnett, Jr, Adrian J Hobbs, Harald H H W Schmidt
Published in: Cardivascular Research, 2021, ISSN 1755-3245
Publisher: Oxford Academic
DOI: 10.1093/cvr/cvab240

Online bias-aware disease module mining with ROBUST-Web

Author(s): Suryadipto Sarkar, Marta Lucchetta, Andreas Maier, Mohamed M Abdrabbou, Jan Baumbach, Markus List, Martin H Schaefer, David B Blumenthal
Published in: Bioinformatics, Issue Volume 39, Issue 6, 2023, ISSN 1367-4811
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btad345

Un-biased housekeeping gene panel selection for high-validity gene expression analysis

Author(s): Casas, A.I., Hassan, A.A., Manz, Q. et al.
Published in: Sci Rep 12, 12324, 2022, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-022-15989-8

Re-Addressing Dementia by Network Medicine and Mechanism-Based Molecular Endotypes

Author(s): Pacheco Pachado, Mayra; Casas, Ana I.; Elbatreek, Mahmoud H.; Nogales, Cristian; Guney, Emre; Espay, Alberto J.; Schmidt, Harald H.H.W.
Published in: Journal of Alzheimer's Disease, Issue vol. 96, no. 1, 2023, Page(s) pp. 47-56, 2023, ISSN 1387-2877
Publisher: IOS Press
DOI: 10.3233/jad-230694

netDx: Software for building interpretable patient classifiers by multi-'omic data integration using patient similarity networks

Author(s): Shraddha Pai, Philipp Weber, Ruth Isserlin, Hussam Kaka, Shirley Hui, Muhammad Ahmad Shah, Luca Giudice, Rosalba Giugno, Anne Krogh Nøhr, Jan Baumbach, Gary D. Bader
Published in: F1000Research, Issue 9, 2020, Page(s) 1239, ISSN 2046-1402
Publisher: F1000 Research Ltd.
DOI: 10.12688/f1000research.26429.2

Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis

Author(s): Florence Ho; Anna M. D. Watson; Mahmoud H. Elbatreek; Pamela W. M. Kleikers; Waheed Khan; Karly C. Sourris; Aozhi Dai; Jay Jha; Harald H. H. W. Schmidt; Karin A. M. Jandeleit-Dahm
Published in: Sci Rep 12, 11570, 2022, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-022-15706-5

NOX5-induced uncoupling of endothelial NO synthase is a causal mechanism and theragnostic target of an age-related hypertension endotype

Author(s): Mahmoud H. Elbatreek, Sepideh Sadegh, Elisa Anastasi, Emre Guney, Cristian Nogales, Tim Kacprowski, Ahmed A. Hassan, Andreas Teubner, Po-Hsun Huang, Chien-Yi Hsu, Paul M. H. Schiffers, Ger M. Janssen, Pamela W. M. Kleikers, Anil Wipat, Jan Baumbach, Jo G. R. De Mey, Harald H. H. W. Schmidt
Published in: PLOS Biology, Issue 18/11, 2020, Page(s) e3000885, ISSN 1545-7885
Publisher: PLOS Biology
DOI: 10.1371/journal.pbio.3000885

Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing

Author(s): Sepideh Sadegh, Julian Matschinske, David B. Blumenthal, Gihanna Galindez, Tim Kacprowski, Markus List, Reza Nasirigerdeh, Mhaned Oubounyt, Andreas Pichlmair, Tim Daniel Rose, Marisol Salgado-Albarrán, Julian Späth, Alexey Stukalov, Nina K. Wenke, Kevin Yuan, Josch K. Pauling, Jan Baumbach
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-17189-2

Robust disease module mining via enumeration of diverse prize-collecting Steiner trees

Author(s): Judith Bernett, Dominik Krupke, Sepideh Sadegh, Jan Baumbach, Sándor P Fekete, Tim Kacprowski, Markus List, David B Blumenthal
Published in: Bioinformatics, 2022, ISSN 1460-2059
Publisher: Oxford Academics

Online in silico validation of disease and gene sets, clusterings, or subnetworks with DIGEST

Author(s): Klaudia Adamowicz; Andreas Maier; Jan Baumbach; David Blumenthal
Published in: Briefings in Bioinformatics, Issue Volume 23, Issue 4, 2022, ISSN 1477-4054
Publisher: Oxford University Press
DOI: 10.14293/s2199-1006.1.sor-.ppp32eqz.v1

Lacking mechanistic disease definitions and corresponding association data hamper progress in network medicine and beyond

Author(s): Sepideh Sadegh; James Skelton; Elisa Anastasi; Andreas Maier; Klaudia Adamowicz; Anna Möller; Nils M. Kriege; Jaanika Kronberg; Toomas Haller; Tim Kacprowski; Anil Wipat; Jan Baumbach; David B. Blumenthal
Published in: Nat Commun, Issue 14, 1662, 2023, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-023-37349-4

Network and Systems Medicine: Position Paper of the European Collaboration on Science and Technology Action on Open Multiscale Systems Medicine

Author(s): Blandine Comte, Jan Baumbach, Arriel Benis, José Basílio, Nataša Debeljak, Åsmund Flobak, Christian Franken, Nissim Harel, Feng He, Martin Kuiper, Juan Albino Méndez Pérez, Estelle Pujos-Guillot, Tadeja Režen, Damjana Rozman, Johannes A. Schmid, Jeanesse Scerri, Paolo Tieri, Kristel Van Steen, Sona Vasudevan, Steven Watterson, Harald H.H.W. Schmidt
Published in: Network and Systems Medicine, Issue 3/1, 2020, Page(s) 67-90, ISSN 2690-5949
Publisher: Mary Ann Liebert, Inc.
DOI: 10.1089/nsm.2020.0004

Network medicine for disease module identification and drug repurposing with the NeDRex platform

Author(s): Sepideh Sadegh, James Skelton, Elisa Anastasi, Judith Bernett, David B. Blumenthal, Gihanna Galindez, Marisol Salgado-Albarrán, Olga Lazareva, Keith Flanagan, Simon Cockell, Cristian Nogales, Ana I. Casas, Harald H. H. W. Schmidt, Jan Baumbach, Anil Wipat & Tim Kacprowski
Published in: Nature Communications, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-27138-2

Molecular networks in Network Medicine: Development and applications

Author(s): Edwin K. Silverman, Harald H. H. W. Schmidt, Eleni Anastasiadou, Lucia Altucci, Marco Angelini, Lina Badimon, Jean-Luc Balligand, Giuditta Benincasa, Giovambattista Capasso, Federica Conte, Antonella Di Costanzo, Lorenzo Farina, Giulia Fiscon, Laurent Gatto, Michele Gentili, Joseph Loscalzo, Cinzia Marchese, Claudio Napoli, Paola Paci, Manuela Petti, John Quackenbush, Paolo Tieri, Davide Viggiano,
Published in: Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2020, Page(s) e1489, ISSN 1939-5094
Publisher: John Wiley and Sons Inc.
DOI: 10.1002/wsbm.1489

Isoform-selective NADPH oxidase inhibitor panel for pharmacological target validation

Author(s): Vu Thao-Vi Dao, Mahmoud H. Elbatreek, Sebastian Altenhöfer, Ana I. Casas, Mayra P. Pachado, Christopher T. Neullens, Ulla G. Knaus, Harald H.H.W. Schmidt
Published in: Free Radical Biology and Medicine, Issue 148, 2020, Page(s) 60-69, ISSN 0891-5849
Publisher: Elsevier BV
DOI: 10.1016/j.freeradbiomed.2019.12.038

Cancer driver drug interaction explorer

Author(s): Michael Hartung; Elisa Anastasi; Zeinab M Mamdouh; Cristian Nogales; Harald H H W Schmidt; Jan Baumbach; Olga Zolotareva; Markus List
Published in: Nucleic Acids Research, Issue Volume 50, Issue W1, 5 July 2022,, 2022, Page(s) Pages W138–W144, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkac384

Thromboinflammation in Brain Ischemia: Recent Updates and Future Perspectives

Author(s): Simon F. De Meyer, PhD, Friederike Langhauser, PhD, Steffen Haupeltshofer, PhD, Christoph Kleinschnitz, MD, PhD, Ana I. Casas, PhD
Published in: Stroke, Issue 53(5), 2022, Page(s) 1487-1499, ISSN 1524-4628
Publisher: AHA/ASA Journals
DOI: 10.1161/strokeaha.122.038733

Network pharmacology: curing causal mechanisms instead of treating symptoms.

Author(s): Nogales C, Mamdouh ZM, List M, Kiel C, Casas AI, and Schmidt HHHW.
Published in: Trends in Pharmacological Sciences, Issue Vol. 43, No. 2, 2021, ISSN 1873-3735
Publisher: Cell Press - Elsevier Inc.
DOI: 10.1016/j.tips.2021.11.004

Conference proceedings (4)

NeDRex - an integrative and interactive network medicine platform for drug repurposing

Author(s): Sadegh S et al.
Published in: Drgu Repurposing Central - Science Open, Issue Conference name: RExPO22 Conference date: 2-3 September, 2022, 2022
Publisher: Drgu Repurposing Central - Science Open
DOI: 10.14293/s2199-1006.1.sor-.pppy90r8.v1

A plug-and-play solution to bring network exploration and drug repurposing to biomedical web platforms

Author(s): Maier A et al.
Published in: Drug Repurposing Central - Science Open, Issue Conference name: RExPO22 Conference date: 2-3 September, 2022, 2022
Publisher: Drug Repurposing Central - Science Open
DOI: 10.14293/s2199-1006.1.sor-.pppvbd8w.v1

Network pharmacology and drug repurposing pave the way for precision oncology

Author(s): Mamdouh Z et al.
Published in: Drug Repurposing Central - Science Open, Issue Conference name: RExPO22 Conference date: 2-3 September, 2022, 2022
Publisher: Drug Repurposing Central - Science Open
DOI: 10.14293/s2199-1006.1.sor-.pppdgtlb.v1

Repurposing soluble guanylate cyclase stimulators from one to another isoform within the ROCG signalling module

Author(s): Alexandra Petraina, Mahmoud H Elbatreek and Christin Elgert et al.
Published in: Drug Repurposing Central - ScienceOpen, Issue Conference name: RExPO22 Conference date: 2-3 September, 2022, 2022
Publisher: Drug Repurposing Central - ScienceOpen
DOI: 10.14293/s2199-1006.1.sor-.pppux7cj.v1

Book chapters (2)

Nitric Oxide Synthase Inhibitors into the Clinic at Last

Author(s): Vu Thao-Vi Dao, Mahmoud H. Elbatreek, Thomas Fuchß, Ulrich Grädler, Harald H. H. W. Schmidt, Ajay M. Shah, Alan Wallace, Richard Knowles
Published in: Reactive Oxygen Species - Network Pharmacology and Therapeutic Applications, Issue 264, 2021, Page(s) 169-204, ISBN 978-3-030-68509-6
Publisher: Springer International Publishing
DOI: 10.1007/164_2020_382

NOX Inhibitors: From Bench to Naxibs to Bedside

Author(s): Mahmoud H. Elbatreek, Hermann Mucke, Harald H. H. W. Schmidt
Published in: Reactive Oxygen Species - Network Pharmacology and Therapeutic Applications, Issue 264, 2021, Page(s) 145-168, ISBN 978-3-030-68509-6
Publisher: Springer International Publishing
DOI: 10.1007/164_2020_387