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A comprehensive mec...
A comprehensive mechanistic model of adipocyte signaling with layers of confidence
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- Lövfors, William, 1991- (author)
- Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Biomedical Engineering, Linköping University, Linköping, Sweden; Department of Mathematics, Linköping University, Linköping, Sweden; School of Medical Sciences and Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden,Avdelningen för medicinsk teknik,Matematiska institutionen,Tekniska fakulteten,Orebro Univ, Sweden; Orebro Univ, Sweden
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- Magnusson, Rasmus, 1992- (author)
- Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Translationell Bioinformatik, Translational Bioinformatics,School of Bioscience, Systems Biology Research Center, University of Skövde, Skövde, Sweden,Univ Skovde, Sweden
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- Jönsson, Cecilia (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Avdelningen för medicinsk teknik,Medicinska fakulteten
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- Gustafsson, Mika (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Olofsson, Charlotta S, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Cedersund, Gunnar, Associate Professor, 1978- (author)
- Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Biomedical Engineering, Linköping University, Linköping, Sweden; School of Medical Sciences and Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden,Avdelningen för medicinsk teknik,Tekniska fakulteten,Centrum för medicinsk bildvetenskap och visualisering, CMIV
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- Nyman, Elin (author)
- Linköpings universitet,Avdelningen för medicinsk teknik,Tekniska fakulteten
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- English.
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In: npj Systems Biology and Applications. - : Springer Nature. - 2056-7189. ; 9:1
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Abstract
Subject headings
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- Adipocyte signaling, normally and in type 2 diabetes, is far from fully understood. We have earlier developed detailed dynamic mathematical models for several well-studied, partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response. For a broader coverage of the response, large-scale phosphoproteomic data and systems level knowledge on protein interactions are key. However, methods to combine detailed dynamic models with large-scale data, using information about the confidence of included interactions, are lacking. We have developed a method to first establish a core model by connecting existing models of adipocyte cellular signaling for: (1) lipolysis and fatty acid release, (2) glucose uptake, and (3) the release of adiponectin. Next, we use publicly available phosphoproteome data for the insulin response in adipocytes together with prior knowledge on protein interactions, to identify phosphosites downstream of the core model. In a parallel pairwise approach with low computation time, we test whether identified phosphosites can be added to the model. We iteratively collect accepted additions into layers and continue the search for phosphosites downstream of these added layers. For the first 30 layers with the highest confidence (311 added phosphosites), the model predicts independent data well (70–90% correct), and the predictive capability gradually decreases when we add layers of decreasing confidence. In total, 57 layers (3059 phosphosites) can be added to the model with predictive ability kept. Finally, our large-scale, layered model enables dynamic simulations of systems-wide alterations in adipocytes in type 2 diabetes.
Subject headings
- NATURVETENSKAP -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)
- NATURAL SCIENCES -- Computer and Information Sciences -- Bioinformatics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
Keyword
- Bioinformatik
- Bioinformatics
Publication and Content Type
- ref (subject category)
- art (subject category)
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