Dissolution of spiral wave ’s core using cardiac optogenetics
by Sayedeh Hussaini, Sarah L. L ädke, Johannes Schröder-Schetelig, Vishalini Venkatesan, Raúl A. Quiñonez Uribe, Claudia Richter, Rupamanjari Majumder, Stefan Luther
Rotating spiral waves in the heart are associated with life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation. These arrhythmias are treated by a process called defibrillation, which forces electrical resynchronization of the heart tissue by delivering a single global high-voltage shock directly to the heart. This method leads to immediate termination of spiral waves. However, this may not be the only mechanism underlying su...
Source: PLoS Computational Biology - December 7, 2023 Category: Biology Authors: Sayedeh Hussaini Source Type: research
multi-GPA-Tree: Statistical approach for pleiotropy informed and functional annotation tree guided prioritization of GWAS results
by Aastha Khatiwada, Ayse Selen Yilmaz, Bethany J. Wolf, Maciej Pietrzak, Dongjun Chung
Genome-wide association studies (GWAS) have successfully identified over two hundred thousand genotype-trait associations. Yet some challenges remain. First, complex traits are often associated with many single nucleotide polymorphisms (SNPs), most with small or moderate effect sizes, making them difficult to detect. Second, many complex traits share a common genetic basis due to ‘pleiotropy’ and and though few methods consider it, leveraging pleiotropy can improve statistical power to detect genotype-trait associations with weaker...
Source: PLoS Computational Biology - December 7, 2023 Category: Biology Authors: Aastha Khatiwada Source Type: research
Major depressive disorder and bistability in an HPA-CNS toggle switch
by Ben Ron Mizrachi, Avichai Tendler, Omer Karin, Tomer Milo, Dafna Haran, Avi Mayo, Uri Alon
Major depressive disorder (MDD) is the most common psychiatric disorder. It has a complex and heterogeneous etiology. Most treatments take weeks to show effects and work well only for a fraction of the patients. Thus, new concepts are needed to understand MDD and its dynamics. One of the strong correlates of MDD is increased activity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which produces the stress hormone cortisol. Existing mathematical models of the HPA axis describe its operation on the scale of hour...
Source: PLoS Computational Biology - December 6, 2023 Category: Biology Authors: Ben Ron Mizrachi Source Type: research
Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics
by Clare P. McCormack, Olivia Goethals, Nele Goeyvaerts, Xavier D. Woot de Trixhe, Peggy Geluykens, Doortje Borrenberghs, Neil M. Ferguson, Oliver Ackaert, Ilaria Dorigatti
Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates. Here, using a mechanistic viral kinetic model calibrated against viral RNA data from experimentalin-vitro infection studies, we assess thein-vitro inhibitory effect of JNJ-1802 by characteri...
Source: PLoS Computational Biology - December 6, 2023 Category: Biology Authors: Clare P. McCormack Source Type: research
RMDGCN: Prediction of RNA methylation and disease associations based on graph convolutional network with attention mechanism
In this study, we proposed a computational method for predicting the associations of RNA methylation and disease based on graph convolutional network (RMDGCN) with attention mechanism. We build an adjacency matrix through the collected m1As and diseases associations, and use positive-unlabeled learning to increase the number of positive samples. By extracting the features of m1As and diseases, a heterogeneous network is constructed, and a GCN with attention mechanism is adopted to predict the associations between m1As and diseases. The experimental results indicate that under a 5-fold cross validation, RMDGCN is superior t...
Source: PLoS Computational Biology - December 6, 2023 Category: Biology Authors: Lian Liu Source Type: research
A cell-and-plasma numerical model reveals hemodynamic stress and flow adaptation in zebrafish microvessels after morphological alteration
In this study, we have developed a cell-and-plasma blood transport model using computational fluid dynamics (CFD) to understand how red blood cell (RBC) partitioning affect lumen wall shear stress (WSS) and blood pressure in zebrafish trunk blood vascular networks with altered rheology and morphology. By performing live imaging of embryos with reduced hematocrit, we discovered that cardiac output and caudal artery flow rates were maintained. These adaptation trends were recapitulated in our CFD models, which showed reduction in network WSS via viscosity reduction in the caudal artery/vein and via pressure gradient weakenin...
Source: PLoS Computational Biology - December 4, 2023 Category: Biology Authors: Swe Soe Maung Ye Source Type: research
Programming co-assembled peptide nanofiber morphology via anionic amino acid type: Insights from molecular dynamics simulations
by Xin Dong, Renjie Liu, Dillon T. Seroski, Gregory A. Hudalla, Carol K. Hall
Co-assembling peptides can be crafted into supramolecular biomaterials for use in biotechnological applications, such as cell culture scaffolds, drug delivery, biosensors, and tissue engineering. Peptide co-assembly refers to the spontaneous organization of two different peptides into a supramolecular architecture. Here we use molecular dynamics simulations to quantify the effect of anionic amino acid type on co-assembly dynamics and nanofiber structure in binary CATCH(+/-) peptide systems. CATCH peptide sequences follow a general pattern: CQCFC...
Source: PLoS Computational Biology - December 4, 2023 Category: Biology Authors: Xin Dong Source Type: research
resevol: An R package for spatially explicit models of pesticide resistance given evolving pest genomes
We present the key features of the resevol package and demonstrate its use for a simple example simulating pests with two covarying traits. The resevol R package is open source under GNU Public License. All source code and documentation are available on GitHub. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - December 4, 2023 Category: Biology Authors: A. Bradley Duthie Source Type: research
Effective cell membrane tension protects red blood cells against malaria invasion
In this study, we use a theoretical model for lipid bilayer mechanics, cytoskeleton deformation, and membrane-merozoite interactions to systematically investigate the influence of effective RBC membrane tension, which includes contributions from the lipid bilayer tension, spontaneous tension, interfacial tension, and the resistance of cytoskeleton against shear deformation on the progression of membrane wrapping during the process of malaria invasion. Our model reveals that this effective membrane tension creates a wrapping energy barrier for a complete merozoite entry. We calculate the tension threshold required to impede...
Source: PLoS Computational Biology - December 4, 2023 Category: Biology Authors: Haleh Alimohamadi Source Type: research
Sparsity in an artificial neural network predicts beauty: Towards a model of processing-based aesthetics
by Nicolas M. Dibot, Sonia Tieo, Tamra C. Mendelson, William Puech, Julien P. Renoult
Generations of scientists have pursued the goal of defining beauty. While early scientists initially focused on objective criteria of beauty ( ‘feature-based aesthetics’), philosophers and artists alike have since proposed that beauty arises from the interaction between the object and the individual who perceives it. The aesthetic theory of fluency formalizes this idea of interaction by proposing that beauty is determined by the effici ency of information processing in the perceiver’s brain (‘processing-based aesthetics’), and ...
Source: PLoS Computational Biology - December 4, 2023 Category: Biology Authors: Nicolas M. Dibot Source Type: research
Spatial exclusion leads to “tug-of-war” ecological dynamics between competing species within microchannels
by Jeremy Rothschild, Tianyi Ma, Joshua N. Milstein, Anton Zilman
Competition is ubiquitous in microbial communities, shaping both their spatial and temporal structure and composition. Classical minimal models of competition, such as the Moran model, have been employed in ecology and evolutionary biology to understand the role of fixation and invasion in the maintenance of population diversity. Informed by recent experimental studies of cellular competition in confined spaces, we extend the Moran model to incorporate mechanical interactions between cells that divide within the limited space of a one-dimensional open micro...
Source: PLoS Computational Biology - December 1, 2023 Category: Biology Authors: Jeremy Rothschild Source Type: research
Learning massive interpretable gene regulatory networks of the human brain by merging Bayesian networks
We present the Fast Greedy Equivalence Search (FGES)-Merge, a new method for learning the structure of gene regulatory networks via merging locally learned Bayesian networks, based on the fast greedy equivalent search algorithm. The method is competitive with the state of the art in terms of the Matthews correlation coefficient, which takes into account both precision and recall, while also improving upon it in terms of speed, scaling up to tens of thousands of variables and being able to use empirical knowledge about the topological structure of gene regulatory networks. To showcase the ability of our method to scale to m...
Source: PLoS Computational Biology - December 1, 2023 Category: Biology Authors: Niko Bernaola Source Type: research
Prokaryotic virus host prediction with graph contrastive augmentaion
by Zhi-Hua Du, Jun-Peng Zhong, Yun Liu, Jian-Qiang Li
Prokaryotic viruses, also known as bacteriophages, play crucial roles in regulating microbial communities and have the potential for phage therapy applications. Accurate prediction of phage-host interactions is essential for understanding the dynamics of these viruses and their impacts on bacterial populations. Numerous computational methods have been developed to tackle this challenging task. However, most existing prediction models can be constrained due to the substantial number of unknown interactions in comparison to the constrained diversity of available training...
Source: PLoS Computational Biology - December 1, 2023 Category: Biology Authors: Zhi-Hua Du Source Type: research
Metamodelling of a two-population spiking neural network
by Jan-Eirik W. Skaar, Nicolai Haug, Alexander J. Stasik, Gaute T. Einevoll, Kristin T øndel
In computational neuroscience, hypotheses are often formulated as bottom-up mechanistic models of the systems in question, consisting of differential equations that can be numerically integrated forward in time. Candidate models can then be validated by comparison against experimental data. The model outputs of neural network models depend on both neuron parameters, connectivity parameters and other model inputs. Successful model fitting requires sufficient exploration of the model parameter space, which can be computationally de...
Source: PLoS Computational Biology - November 30, 2023 Category: Biology Authors: Jan-Eirik W. Skaar Source Type: research
Fluctuations in auxin levels depend upon synchronicity of cell divisions in a one-dimensional model of auxin transport
by Simon Bellows, George Janes, Daniele Avitabile, John R. King, Anthony Bishopp, Etienne Farcot
Auxin is a well-studied plant hormone, the spatial distribution of which remains incompletely understood. Here, we investigate the effects of cell growth and divisions on the dynamics of auxin patterning, using a combination of mathematical modelling and experimental observations. In contrast to most prior work, models are not designed or tuned with the aim to produce a specific auxin pattern. Instead, we use well-established techniques from dynamical systems theory to uncover and classify ranges of auxin patterns as exhaustiv...
Source: PLoS Computational Biology - November 30, 2023 Category: Biology Authors: Simon Bellows Source Type: research
