| 1. |
- Cho, Kwang-Hyun, et al.
(författare)
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A hybrid systems framework for cellular processes
- 2005
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Ingår i: Biosystems (Amsterdam. Print). - : Elsevier BV. - 0303-2647 .- 1872-8324. ; 80:3, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- With the availability of technologies that allow us to obtain stimulus-response time series data for modeling and system identification, there is going to be an increasing need for conceptual frameworks in which to formulate and test hypotheses about intra- and inter-cellular dynamics, in general and not just dependent on a particular cell line, cell type, organism, or technology. While the semantics can be quite different, biologists and systems scientists use in many cases a similar language (notion of feedback, regulation, etc.). A more abstract system-theoretic framework for signals, systems, and control could provide the biologist with an interface between the domains. Apart from recent examples to identify functional elements and describing them in engineering terms, there have been various more abstract developments to describe dynamics at the cell level in the past. This includes Rosen's (M,R)-systems. This paper presents an abstract and general compact mathematical framework of intracellular dynamics, regulation and regime switching inspired by (M,R)-theory and based on hybrid automata.
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| 2. |
- Frey, Simone, et al.
(författare)
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How quantitative measures unravel design principles in multi-stage phosphorylation cascades.
- 2008
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Ingår i: Journal of theoretical biology. - : Elsevier BV. - 1095-8541 .- 0022-5193. ; 254:1, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- We investigate design principles of linear multi-stage phosphorylation cascades by using quantitative measures for signaling time, signal duration and signal amplitude. We compare alternative pathway structures by varying the number of phosphorylations and the length of the cascade. We show that a model for a weakly activated pathway does not reflect the biological context well, unless it is restricted to certain parameter combinations. Focusing therefore on a more general model, we compare alternative structures with respect to a multivariate optimization criterion. We test the hypothesis that the structure of a linear multi-stage phosphorylation cascade is the result of an optimization process aiming for a fast response, defined by the minimum of the product of signaling time and signal duration. It is then shown that certain pathway structures minimize this criterion. Several popular models of MAPK cascades form the basis of our study. These models represent different levels of approximation, which we compare and discuss with respect to the quantitative measures.
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| 3. |
- Henkel, Ron, et al.
(författare)
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Finding patterns in biochemical reaction networks
- 2016
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Ingår i: PeerJ Preprints. - : PeerJ. - 2167-9843. ; 4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Computational models in biology encode molecular and cell biological processes. Many of them can be represented as biochemical reaction networks. Studying such networks, one is often interested in systems that share similar reactions and mechanisms. Typical goals are to understand the parts of a model, to identify reoccurring patterns, and to find biologically relevant motifs. The large number of models are available for such a search, but also the large size of models require automated methods. Specifically the generic problem of finding patterns in large networks is computationally hard. As a consequence, only partial solutions for a structural analysis of models exist. Here we introduce a tool chain that identifies reoccurring patterns in biochemical reaction networks. We started this work with an evaluation of algorithms for the identification of frequent subgraphs. Then, we created graph representations of existing SBML models and ran the most suitable algorithm on the data. The result was a list of reaction patterns together with statistics about the occurrence of each pattern in the data set. The approach was validated with 575 SBML models from the curated branch of BioModels. We analysed how the resulting patterns confirm with expectations from the literature and from previous model statistics. In the future, the identified patterns can serve as a tool to measure the similarity of models
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| 4. |
- Lambusch, Fabienne, et al.
(författare)
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Identifying frequent patterns in biochemical reaction networks : a workflow
- 2018
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Ingår i: Database. - : Oxford University Press (OUP). - 1758-0463. ; 2018
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Tidskriftsartikel (refereegranskat)abstract
- Computational models in biology encode molecular and cell biological processes. Many of these models can be represented as biochemical reaction networks. Studying such networks, one is mostly interested in systems that share similar reactions and mechanisms. Typical goals of an investigation thus include understanding of model parts, identification of reoccurring patterns and recognition of biologically relevant motifs. The large number and size of available models, however, require automated methods to support researchers in achieving their goals. Specifically for the problem of finding patterns in large networks only partial solutions exist. We propose a workflow that identifies frequent structural patterns in biochemical reaction networks encoded in the Systems Biology Markup Language. The workflow utilizes a subgraph mining algorithm to detect the network patterns. Once patterns are identified, the textual pattern description can automatically be converted into a graphical representation. Furthermore, information about the distribution of patterns among a selected set of models can be retrieved. The workflow was validated with 575 models from the curated branch of BioModels. In this paper, we highlight interesting and frequent structural patterns. Furthermore, we provide exemplary patterns that incorporate terms from the Systems Biology Ontology. Our workflow can be applied to a custom set of models or to models already existing in our graph database MaSyMoS. The occurrences of frequent patterns may give insight into the encoding of central biological processes, evaluate postulated biological motifs or serve as a similarity measure for models that share common structures.
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| 5. |
- Ostaszewski, Marek, et al.
(författare)
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COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
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Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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| 6. |
- Serhan, Charles N., et al.
(författare)
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The Atlas of Inflammation Resolution (AIR)
- 2020
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Ingår i: Molecular Aspects of Medicine. - : Elsevier. - 0098-2997 .- 1872-9452. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi- and interdisciplinary approach necessary. The Atlas of Inflammation Resolution (AIR) is a web-based resource capturing an essential part of the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. By mapping experimental data onto the AIR, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards. The AIR was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses. The AIR is accessible through https://air.bio.informatik.uni-rostock.de.
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