scholarly journals Parallel Tempering with Lasso for Model Reduction in Systems Biology

2019 ◽  
Author(s):  
Sanjana Gupta ◽  
Robin E.C. Lee ◽  
James R. Faeder
Keyword(s):  
Systems Biology ◽  
Model Reduction ◽  
Feedback Loops ◽  
Signaling Network ◽  
Parallel Tempering ◽  
Emergent Properties ◽  
Signaling Systems ◽  
Cellular Behaviors ◽  
Complex Signaling ◽  
The Bayesian Approach

AbstractSystems Biology models reveal relationships between signaling inputs and observable molecular or cellular behaviors. The complexity of these models, however, often obscures key elements that regulate emergent properties. We use a Bayesian model reduction approach that combines Parallel Tempering with Lasso regularization to identify minimal subsets of reactions in a signaling network that are sufficient to reproduce experimentally observed data. The Bayesian approach finds distinct reduced models that fit data equivalently. A variant of this approach based on Group Lasso is applied to the NF-κB signaling network to test the necessity of feedback loops for responses to pulsatile and continuous pathway stimulation. Taken together, our results demonstrate that Bayesian parameter estimation combined with regularization can isolate and reveal core motifs sufficient to explain data from complex signaling systems.

Emergence

2017 ◽  
Author(s):  
Matthew Croasmun
Keyword(s):  
Systems Biology ◽  
Philosophy Of Science ◽  
Downward Causation ◽  
Feedback Loops ◽  
Emergent Properties ◽  
Middle Ground ◽  
Emergence Theory ◽  
Multiple Levels ◽  
Causal Structures

Emergence theory in philosophy of science is introduced, first in modest terms of the emergent properties exhibited by complex wholes that are not exhibited by their constituent parts. Then, emergence is treated as a trans-ordinal theory that stakes out a middle ground between reductionism and dualism. The tension between supervenience and downward causation is described as the generative dialectic of emergence. The coherence of downward causation is debated and ultimately affirmed on account of the prevalence of downward causation in the sorts of accounts produced by fields like systems biology. Racism is treated as a case study of the sorts of causal feedback loops generated by complex causal structures that operate at multiple levels of hierarchy.

scholarly journals Parallel Tempering with Lasso for model reduction in systems biology

2020 ◽  
Vol 16 (3) ◽  
pp. e1007669 ◽  
Author(s):  
Sanjana Gupta ◽  
Robin E. C. Lee ◽  
James R. Faeder
Keyword(s):  
Systems Biology ◽  
Model Reduction ◽  
Parallel Tempering

Look Closely, the Beautiful May Be Small: Precursor-Derived Peptides in Plants

2019 ◽  
Vol 70 (1) ◽  
pp. 153-186 ◽  
Author(s):  
Vilde Olsson ◽  
Lisa Joos ◽  
Shanshuo Zhu ◽  
Kris Gevaert ◽  
Melinka A. Butenko ◽  
...  
Keyword(s):  
Cell Communication ◽  
Peptide Ligands ◽  
Biologically Active ◽  
Peptide Ligand ◽  
Long Distance ◽  
Signaling Systems ◽  
Experimental Approaches ◽  
Biologically Active Peptide ◽  
Subsequent Activation ◽  
Complex Signaling

During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here, we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs. We discuss different experimental approaches that can be used to match peptide ligands with their receptors. Lastly, we explore how peptides evolved from basic signaling units regulating essential processes in plants to more complex signaling systems as new adaptive traits developed and how nonplant organisms exploit this signaling machinery by producing peptide mimics.

scholarly journals Digital signaling network drives the assembly of the AIM2-ASC inflammasome

2018 ◽  
Vol 115 (9) ◽  
pp. E1963-E1972 ◽  
Author(s):  
Mariusz Matyszewski ◽  
Seamus R. Morrone ◽  
Jungsan Sohn
Keyword(s):  
Host Defense ◽  
Positive Feedback ◽  
Signal Amplification ◽  
Molecular Level ◽  
Design Principles ◽  
Digital Circuit ◽  
Quantitative Model ◽  
Feedback Loops ◽  
Signaling Network

The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.

Cancerous perturbations within the ERK, PI3K/Akt, and Wnt/β-catenin signaling network constitutively activate inter-pathway positive feedback loops

2017 ◽  
Vol 13 (5) ◽  
pp. 830-840 ◽  
Author(s):  
Rahul Rao Padala ◽  
Rishabh Karnawat ◽  
Satish Bharathwaj Viswanathan ◽  
Abhishek Vijay Thakkar ◽  
Asim Bikas Das
Keyword(s):  
Signaling Pathways ◽  
Malignant Transformation ◽  
Positive Feedback ◽  
Feedback Loops ◽  
Signaling Network ◽  
Molecular Signaling ◽  
Activated State ◽  
Molecular Signaling Pathways

Perturbations in molecular signaling pathways result in a constitutively activated state, leading to malignant transformation of cells.

scholarly journals Complex Signaling Network in Regulation of Adenosine 5′-Phosphosulfate Reductase by Salt Stress in Arabidopsis Roots

2008 ◽  
Vol 146 (3) ◽  
pp. 1408-1420 ◽  
Author(s):  
Anna Koprivova ◽  
Kathryn Anne North ◽  
Stanislav Kopriva
Keyword(s):  
Salt Stress ◽  
Signaling Network ◽  
Complex Signaling

scholarly journals Function and Evolution of Nuclear Receptors in Environmental-Dependent Postembryonic Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Jan Taubenheim ◽  
Constantin Kortmann ◽  
Sebastian Fraune
Keyword(s):  
Nuclear Receptors ◽  
Sexual Maturation ◽  
Steroid Receptors ◽  
Current Knowledge ◽  
Postembryonic Development ◽  
Model Organisms ◽  
Signaling Mechanism ◽  
Signaling Systems ◽  
Decision Points ◽  
Complex Signaling

Nuclear receptors (NRs) fulfill key roles in the coordination of postembryonal developmental transitions in animal species. They control the metamorphosis and sexual maturation in virtually all animals and by that the two main environmental-dependent developmental decision points. Sexual maturation and metamorphosis are controlled by steroid receptors and thyroid receptors, respectively in vertebrates, while both processes are orchestrated by the ecdysone receptor (EcR) in insects. The regulation of these processes depends on environmental factors like nutrition, temperature, or photoperiods and by that NRs form evolutionary conserved mediators of phenotypic plasticity. While the mechanism of action for metamorphosis and sexual maturation are well studied in model organisms, the evolution of these systems is not entirely understood and requires further investigation. We here review the current knowledge of NR involvement in metamorphosis and sexual maturation across the animal tree of life with special attention to environmental integration and evolution of the signaling mechanism. Furthermore, we compare commonalities and differences of the different signaling systems. Finally, we identify key gaps in our knowledge of NR evolution, which, if sufficiently investigated, would lead to an importantly improved understanding of the evolution of complex signaling systems, the evolution of life history decision points, and, ultimately, speciation events in the metazoan kingdom.

HER2: Biology, Detection, and Clinical Implications

2011 ◽  
Vol 135 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Carolina Gutierrez ◽  
Rachel Schiff
Keyword(s):  
Breast Cancer ◽  
Tumor Development ◽  
Signaling Network ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Treatment Target ◽  
Valuable Treatment ◽  
Basic Biology ◽  
Her2 Signaling ◽  
Complex Signaling

Abstract Context—HER2 is a membrane tyrosine kinase and oncogene that is overexpressed and gene amplified in about 20% of breast cancers. When activated it provides the cell with potent proliferative and antiapoptosis signals and it is the major driver of tumor development and progression for this subset of breast cancer. When shown to be overexpressed or amplified by appropriate methods, HER2 is a valuable treatment target. Objectives—To review the basic biology of the HER2 signaling network, to discuss various approved methods for its detection in clinical specimens, and to describe the impressive results of therapies targeting HER2. Data Sources—Selected literature searchable on PubMed as well as older studies revealed by the literature review were reviewed. Conclusion—HER2 is an important member of a complex signaling network and when gene amplified, it results in an aggressive subtype of breast cancer. Patients with tumors found to overexpress HER2 protein or to be amplified for the gene are candidates for therapy that significantly reduces mortality.

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