Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production
We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV ’s intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutati ons. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model ...
Source: PLoS Computational Biology - February 7, 2024 Category: Biology Authors: Connor R. King Source Type: research
Reconciling ASPP-p53 binding mode discrepancies through an ensemble binding framework that bridges crystallography and NMR data
In this study, we employed multi-scale molecular dynamics (MD) simulations combined with free energy calculations to reconcile the discrepancy in the binding modes. We demonstrated that the binding mode based solely on a single crystal structure does not enable iASPP ’s RT loop to engage with p53’s C-terminal linker—a verified interaction. Instead, an ensemble of simulated iASPP-p53 complexes facilitates this interaction. We showed that the ensemble-average inter-protein contacting residues and NMR-detected interfacial residues qualitatively overlap on ASP P proteins, and the ensemble-average binding free energies be...
Source: PLoS Computational Biology - February 7, 2024 Category: Biology Authors: Te Liu Source Type: research
Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells
by Sarvenaz Sarabipour, Karina Kinghorn, Kaitlyn M. Quigley, Anita Kovacs-Kasa, Brian H. Annex, Victoria L. Bautch, Feilim Mac Gabhann
The vascular endothelial growth factor (VEGF) family of cytokines are key drivers of blood vessel growth and remodeling. These ligands act via multiple VEGF receptors (VEGFR) and co-receptors such as Neuropilin (NRP) expressed on endothelial cells. These membrane-associated receptors are not solely expressed on the cell surface, they move between the surface and intracellular locations, where they can function differently. The location of the receptor alters its ability to ’see’ (acces...
Source: PLoS Computational Biology - February 7, 2024 Category: Biology Authors: Sarvenaz Sarabipour Source Type: research
Index analysis: An approach to understand signal transduction with application to the EGFR signalling pathway
by Jane Kn öchel, Charlotte Kloft, Wilhelm Huisinga
In systems biology and pharmacology, large-scale kinetic models are used to study the dynamic response of a system to a specific input or stimulus. While in many applications, a deeper understanding of the input-response behaviour is highly desirable, it is often hindered by the large number of molecular species and the complexity of the interactions. An approach that identifies key molecular species for a given input-response relationship and characterises dynamic properties of states is therefore highly desirable. We introduce the concept of index analysis; it is base...
Source: PLoS Computational Biology - February 5, 2024 Category: Biology Authors: Jane Kn öchel Source Type: research
Topological data analysis reveals core heteroblastic and ontogenetic programs embedded in leaves of grapevine (Vitaceae) and maracuy á (Passifloraceae)
by Sarah Percival, Joyce G. Onyenedum, Daniel H. Chitwood, Aman Y. Husbands
Leaves are often described in language that evokes a single shape. However, embedded in that descriptor is a multitude of latent shapes arising from evolutionary, developmental, environmental, and other effects. These confounded effects manifest at distinct developmental time points and evolve at different tempos. Here, revisiting datasets comprised of thousands of leaves of vining grapevine (Vitaceae) and maracuy á (Passifloraceae) species, we apply a technique from the mathematical field of topological data analysis to comparatively visualize t...
Source: PLoS Computational Biology - February 5, 2024 Category: Biology Authors: Sarah Percival Source Type: research
Sleep deprivation detected by voice analysis
by Etienne Thoret, Thomas Andrillon, Caroline Gauriau, Damien L éger, Daniel Pressnitzer
Sleep deprivation has an ever-increasing impact on individuals and societies. Yet, to date, there is no quick and objective test for sleep deprivation. Here, we used automated acoustic analyses of the voice to detect sleep deprivation. Building on current machine-learning approaches, we focused on interpretability by introducing two novel ideas: the use of a fully generic auditory representation as input feature space, combined with an interpretation technique based on reverse correlation. The auditory representation consisted of a s...
Source: PLoS Computational Biology - February 5, 2024 Category: Biology Authors: Etienne Thoret Source Type: research
Trained recurrent neural networks develop phase-locked limit cycles in a working memory task
by Matthijs Pals, Jakob H. Macke, Omri Barak
Neural oscillations are ubiquitously observed in many brain areas. One proposed functional role of these oscillations is that they serve as an internal clock, or ‘frame of reference’. Information can be encoded by the timing of neural activity relative to thephase of such oscillations. In line with this hypothesis, there have been multiple empirical observations of suchphase codes in the brain. Here we ask: What kind of neural dynamics support phase coding of information with neural oscillations? We tackled this question by analyzing recurrent neural networks (RNNs) that we...
Source: PLoS Computational Biology - February 5, 2024 Category: Biology Authors: Matthijs Pals Source Type: research
Foldy: An open-source web application for interactive protein structure analysis
by Jacob B. Roberts, Alberto A. Nava, Allison N. Pearson, Matthew R. Incha, Luis E. Valencia, Melody Ma, Abhay Rao, Jay D. Keasling
Foldy is a cloud-based application that allows non-computational biologists to easily utilize advanced AI-based structural biology tools, including AlphaFold and DiffDock. With many deployment options, it can be employed by individuals, labs, universities, and companies in the cloud without requiring hardware resources, but it can also be configured to utilize locally available computers. Foldy enables scientists to predict the structure of proteins and complexes up to 6000 amino acids with A...
Source: PLoS Computational Biology - February 2, 2024 Category: Biology Authors: Jacob B. Roberts Source Type: research
Covering Hierarchical Dirichlet Mixture Models on binary data to enhance genomic stratifications in onco-hematology
by Daniele Dall ’Olio, Eric Sträng, Amin T. Turki, Jesse M. Tettero, Martje Barbus, Renate Schulze-Rath, Javier Martinez Elicegui, Tommaso Matteuzzi, Alessandra Merlotti, Luciana Carota, Claudia Sala, Matteo G. Della Porta, Enrico Giampieri, Jesús María Hernández-Rivas, Lars Bullinger, Gastone Castellani, wit h the HARMONY Healthcare Alliance Consortium
Onco-hematological studies are increasingly adopting statistical mixture models to support the advancement of the genomically-driven classification systems for blood cancer. Targeting enhanced patients stratification based on the sole role of molecular biology attrac...
Source: PLoS Computational Biology - February 2, 2024 Category: Biology Authors: Daniele Dall ’Olio Source Type: research
The geometric evolution of aortic dissections: Predicting surgical success using fluctuations in integrated Gaussian curvature
We present an imaging-based geometric descriptor, inspired by fundamental ideas from topology and soft-matter physics that captures dynamic shape evolution. The aorta is reduced to a two-dimensional mathematical surface in space whose geometry is fully characterized by the local principal curvatures. Disease causes deviation from the smooth bent cylindrical shape of normal aortas, leading to a family of highly heterogeneous surfaces of varying shapes and sizes. To deconvolute changes in shape from size, the shape is characterized using integrated Gaussian curvature or total curvature. The fluctuation in total curvature (δ...
Source: PLoS Computational Biology - February 2, 2024 Category: Biology Authors: Kameel Khabaz Source Type: research
The shapes of elongating gastruloids are consistent with convergent extension driven by a combination of active cell crawling and differential adhesion
by Martijn A. de Jong, Esm ée Adegeest, Noémie M. L. P. Bérenger-Currias, Maria Mircea, Roeland M. H. Merks, Stefan Semrau
Gastruloids have emerged as highly usefulin vitro models of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species. Gastruloids provide an opportunity to study this morphogenic processin vitro. Here, we measure and quantify the shapes of elongating gastruloids and...
Source: PLoS Computational Biology - February 2, 2024 Category: Biology Authors: Martijn A. de Jong Source Type: research
Ten simple rules for designing graphical abstracts
by Helena Klara Jambor, Martin Bornh äuser (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 1, 2024 Category: Biology Authors: Helena Klara Jambor Source Type: research
Modeling geographic vaccination strategies for COVID-19 in Norway
This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two...
Source: PLoS Computational Biology - January 31, 2024 Category: Biology Authors: Louis Yat Hin Chan Source Type: research
Ten simple rules for using large language models in science, version 1.0
by Gabriel Reuben Smith, Carolina Bello, Lalasia Bialic-Murphy, Emily Clark, Camille S. Delavaux, Camille Fournier de Lauriere, Johan van den Hoogen, Thomas Lauber, Haozhi Ma, Daniel S. Maynard, Matthew Mirman, Lidong Mo, Dominic Rebindaine, Josephine Elena Reek, Leland K. Werden, Zhaofei Wu, Gayoung Yang, Qingzhou Zhao, Constantin M. Zohner, Thomas W. Crowther (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - January 31, 2024 Category: Biology Authors: Gabriel Reuben Smith Source Type: research
Statistical integration of multi-omics and drug screening data from cell lines
by Said el Bouhaddani, Matthias H öllerhage, Hae-Won Uh, Claudia Moebius, Marc Bickle, Günter Höglinger, Jeanine Houwing-Duistermaat
Data integration methods are used to obtain a unified summary of multiple datasets. For multi-modal data, we propose a computational workflow to jointly analyze datasets from cell lines. The workflow comprises a novel probabilistic data integration method, named POPLS-DA, for multi-omics data.
The workflow is motivated by a study on synucleinopathies where transcriptomics, proteomics, and drug screening data are measured in affected LUHMES cell lines and controls. The aim is to highlight ...
Source: PLoS Computational Biology - January 31, 2024 Category: Biology Authors: Said el Bouhaddani Source Type: research
