Publications

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5 Publications visible to you, out of a total of 5

Abstract (Expand)

This paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic biology. The COMBINE initiative coordinates the development of various community standards and formats for computational models in the life sciences. Over the past 10 years, COMBINE has brought together standard communities that have further developed and harmonized their standards for better interoperability of models and data. COMBINE 2019 was co-located with a stakeholder workshop of the European EU-STANDS4PM initiative that aims at harmonized data and model standardization for in silico models in the field of personalized medicine, as well as with the FAIRDOM PALs meeting to discuss findable, accessible, interoperable and reusable (FAIR) data sharing. This report briefly describes the work discussed in invited and contributed talks as well as during breakout sessions. It also highlights recent advancements in data, model, and annotation standardization efforts. Finally, this report concludes with some challenges and opportunities that this community will face during the next 10 years.

Authors: Dagmar Waltemath, Martin Golebiewski, Michael L Blinov, Padraig Gleeson, Henning Hermjakob, Michael Hucka, Esther Thea Inau, Sarah M Keating, Matthias König, Olga Krebs, Rahuman S Malik-Sheriff, David Nickerson, Ernst Oberortner, Herbert M Sauro, Falk Schreiber, Lucian Smith, Melanie I Stefan, Ulrike Wittig, Chris J Myers

Date Published: 29th Jun 2020

Publication Type: Journal

Abstract (Expand)

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation.

Authors: Maxwell Lewis Neal, Matthias König, David Nickerson, Göksel Mısırlı, Reza Kalbasi, Andreas Dräger, Koray Atalag, Vijayalakshmi Chelliah, Michael T Cooling, Daniel L Cook, Sharon Crook, Miguel de Alba, Samuel H Friedman, Alan Garny, John H Gennari, Padraig Gleeson, Martin Golebiewski, Michael Hucka, Nick Juty, Chris Myers, Brett G Olivier, Herbert M Sauro, Martin Scharm, Jacky L Snoep, Vasundra Touré, Anil Wipat, Olaf Wolkenhauer, Dagmar Waltemath

Date Published: 1st Mar 2019

Publication Type: Journal

Abstract (Expand)

Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2–5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway.

Authors: Lavanya M Iyer, Sankari Nagarajan, Monique Woelfer, Eric Schoger, Sara Khadjeh, Maria Patapia Zafiriou, Vijayalakshmi Kari, Jonas Herting, Sze Ting Pang, Tobias Weber, Franziska S Rathjens, Thomas H Fischer, Karl Toischer, Gerd Hasenfuss, Claudia Noack, Steven A Johnsen, Laura C Zelarayán

Date Published: 6th Apr 2018

Publication Type: Not specified

Abstract (Expand)

Standards for data exchange are critical to the development of any field. They enable researchers and practitioners to transport information reliably, to apply a variety of tools to their problems, and to reproduce scientific results. Over the past two decades, a range of standards have been developed to facilitate the exchange and reuse of information in the domain of representation and modeling of biological systems. These standards are complementary, so the interactions between their developers increased over time. By the end of the last decade, the community of researchers decided that more interoperability is required between the standards, and that common development is needed to make better use of effort, time, and money devoted to this activity. The COmputational MOdeling in Biology NEtwork (COMBINE) was created to enable the sharing of resources, tools, and other infrastructure. This paper provides a brief history of this endeavor and the challenges that remain.

Authors: Chris J. Myers, Gary Bader, Padraig Gleeson, Martin Golebiewski, Michael Hucka, Nicolas Le Novere, David P. Nickerson, Falk Schreiber, Dagmar Waltemath

Date Published: 1st Dec 2017

Publication Type: InProceedings

Abstract (Expand)

The FAIRDOMHub is a repository for publishing FAIR (Findable, Accessible, Interoperable and Reusable) Data, Operating procedures and Models (https://fairdomhub.org/) for the Systems Biology community. It is a web-accessible repository for storing and sharing systems biology research assets. It enables researchers to organize, share and publish data, models and protocols, interlink them in the context of the systems biology investigations that produced them, and to interrogate them via API interfaces. By using the FAIRDOMHub, researchers can achieve more effective exchange with geographically distributed collaborators during projects, ensure results are sustained and preserved and generate reproducible publications that adhere to the FAIR guiding principles of data stewardship.

Authors: K. Wolstencroft, O. Krebs, J. L. Snoep, N. J. Stanford, F. Bacall, M. Golebiewski, R. Kuzyakiv, Q. Nguyen, S. Owen, S. Soiland-Reyes, J. Straszewski, D. D. van Niekerk, A. R. Williams, L. Malmstrom, B. Rinn, W. Muller, C. Goble

Date Published: 4th Jan 2017

Publication Type: Journal

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