The condition for dynamic stability in humans walking with feedback control
by Hendrik Reimann, Sjoerd M. Bruijn The walking human body is mechanically unstable. Loss of stability and falling is more likely in certain groups of people, such as older adults or people with neuromotor impairments, as well as in certain situations, such as when experiencing conflicting or distracting sensory inputs. Stability during walking is often characterized biomechanically, by measures based on body dynamics and the base of support. Neural control of upright stability, on the other hand, does not factor into commonly used stability measures. Here we analyze stability of human walking accounting for both biomech...
Source: PLoS Computational Biology - March 18, 2024 Category: Biology Authors: Hendrik Reimann Source Type: research

Continuous evaluation of denoising strategies in resting-state fMRI connectivity using fMRIPrep and Nilearn
by Hao-Ting Wang, Steven L. Meisler, Hanad Sharmarke, Natasha Clarke, Nicolas Gensollen, Christopher J. Markiewicz, Fran çois Paugam, Bertrand Thirion, Pierre Bellec Reducing contributions from non-neuronal sources is a crucial step in functional magnetic resonance imaging (fMRI) connectivity analyses. Many viable strategies for denoising fMRI are used in the literature, and practitioners rely on denoising benchmarks for guidance in the selection of an appropriate choice for their study. However, fMRI denoising software is an ever-evolving field, and the benchmarks can quickly become obsolete as the techniques or impleme...
Source: PLoS Computational Biology - March 18, 2024 Category: Biology Authors: Hao-Ting Wang Source Type: research

Impact on backpropagation of the spatial heterogeneity of sodium channel kinetics in the axon initial segment
by Benjamin S. M. Barlow, Andr é Longtin, Béla Joós In a variety of neurons, action potentials (APs) initiate at the proximal axon, within a region called the axon initial segment (AIS), which has a high density of voltage-gated sodium channels (NaVs) on its membrane. In pyramidal neurons, the proximal AIS has been reported to exhibit a higher proportion of NaVs with gating properties that are “right-shifted” to more depolarized voltages, compared to the distal AIS. Further, recent experiments have revealed that as neurons develop, the spatial distribution of NaV subtypes along the AIS can change substantially, sug...
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Benjamin S. M. Barlow Source Type: research

Ensemble dynamics and information flow deduction from whole-brain imaging data
In this study, we applied previously unexplored methodologies to analyze time-lapse 3D imaging (4D imaging) data of head neurons of the nematodeCaenorhabditis elegans. By combining time-delay embedding with the independent component analysis, we successfully decomposed whole-brain activities into a small number of component dynamics. Through the integration of results from multiple samples, we extracted common dynamics from neuronal activities that exhibit apparent divergence across different animals. Notably, while several components show common cooperativity across samples, some component pairs exhibited distinct relatio...
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Yu Toyoshima Source Type: research

Evolutionary graph theory beyond pairwise interactions: Higher-order network motifs shape times to fixation in structured populations
by Yang Ping Kuo, Oana Carja To design population topologies that can accelerate rates of solution discovery in directed evolution problems or for evolutionary optimization applications, we must first systematically understand how population structure shapes evolutionary outcome. Using the mathematical formalism of evolutionary graph theory, recent studies have shown how to topologically build networks of population interaction that increase probabilities of fixation of beneficial mutations, at the expense, however, of longer fixation times, which can slow down rates of evolution, under elevated mutation rate. Here we fin...
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Yang Ping Kuo Source Type: research

For long-term sustainable software in bioinformatics
by Luis Pedro Coelho (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Luis Pedro Coelho Source Type: research

Bayesian inference of relative fitness on high-throughput pooled competition assays
We present a Bayesian pipeline to infer relative microbial fitness from high-throughput lineage tracking assays. Our model accounts for multiple sources of noise and propagates uncertainties throughout all parameters in a systematic way. Furthermore, using modern variational inference methods based on automatic differentiation, we are able to scale the inference to a large number of unique barcodes. We extend this core model to analyze multi-environment assays, replicate experiments, and barcodes linked to genotypes. On simulations, our method recovers known parameters within posterior credible intervals. This work provide...
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Manuel Razo-Mejia Source Type: research

Metabolic symbiosis between oxygenated and hypoxic tumour cells: An agent-based modelling study
by Pahala Gedara Jayathilake, Pedro Victori, Clara E. Pavillet, Chang Heon Lee, Dimitrios Voukantsis, Ana Miar, Anjali Arora, Adrian L. Harris, Karl J. Morten, Francesca M. Buffa Deregulated metabolism is one of the hallmarks of cancer. It is well-known that tumour cells tend to metabolize glucose via glycolysis even when oxygen is available and mitochondrial respiration is functional. However, the lower energy efficiency of aerobic glycolysis with respect to mitochondrial respiration makes this behaviour, namely the Warburg effect, counter-intuitive, although it has now been recognized as source of anabolic precursors. O...
Source: PLoS Computational Biology - March 15, 2024 Category: Biology Authors: Pahala Gedara Jayathilake Source Type: research

An analytically tractable, age-structured model of the impact of vector control on mosquito-transmitted infections
by Emma L. Davis, T. D éirdre Hollingsworth, Matt J. Keeling Vector control is a vital tool utilised by malaria control and elimination programmes worldwide, and as such it is important that we can accurately quantify the expected public health impact of these methods. There are very few previous models that consider vector-control-induced changes in the age-structure of the vector population and the resulting impact on transmission. We analytically derive the steady-state solution of a novel age-structured deterministic compartmental model describing the mosquito feeding cycle, with mosquito age represented discretely b...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Emma L. Davis Source Type: research

Computational prediction of protein interactions in single cells by proximity sequencing
by Junjie Xia, Hoang Van Phan, Luke Vistain, Mengjie Chen, Aly A. Khan, Sava ş Tay Proximity sequencing (Prox-seq) simultaneously measures gene expression, protein expression and protein complexes on single cells. Using information from dual-antibody binding events, Prox-seq infers surface protein dimers at the single-cell level. Prox-seq provides multi-dimensional phenotyping of single cells in high throughput, and was recently used to track the formation of receptor complexes during cell signaling and discovered a novel interaction between CD9 and CD8 in na ïve T cells. The distribution of protein abundance can affect...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Junjie Xia Source Type: research

Mathematical models of < i > Plasmodium vivax < /i > transmission: A scoping review
by Md Nurul Anwar, Lauren Smith, Angela Devine, Somya Mehra, Camelia R. Walker, Elizabeth Ivory, Eamon Conway, Ivo Mueller, James M. McCaw, Jennifer A. Flegg, Roslyn I. HicksonPlasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of theP. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). Mathematical modelling approaches have been widely applied to understan...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Md Nurul Anwar Source Type: research

Combining machine learning with structure-based protein design to predict and engineer post-translational modifications of proteins
by Moritz Ertelt, Vikram Khipple Mulligan, Jack B. Maguire, Sergey Lyskov, Rocco Moretti, Torben Schiffner, Jens Meiler, Clara T. Schoeder Post-translational modifications (PTMs) of proteins play a vital role in their function and stability. These modifications influence protein folding, signaling, protein-protein interactions, enzyme activity, binding affinity, aggregation, degradation, and much more. To date, over 400 types of PTMs have been described, representing chemical diversity well beyond the genetically encoded amino acids. Such modifications pose a challenge to the successful design of proteins, but also repres...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Moritz Ertelt Source Type: research

kCSD-python, reliable current source density estimation with quality control
by Chaitanya Chintaluri, Marta Bejtka, W ładysław Średniawa, Michał Czerwiński, Jakub M. Dzik, Joanna Jędrzejewska-Szmek, Daniel K. Wójcik Interpretation of extracellular recordings can be challenging due to the long range of electric field. This challenge can be mitigated by estimating the current source density (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method and related tools to facilitate CSD analysis of experimental data and the interpretation of results. We show how to counter the limitations imposed by noise and assumptions in the method it...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Chaitanya Chintaluri Source Type: research

CRISPR-M: Predicting sgRNA off-target effect using a multi-view deep learning network
by Jialiang Sun, Jun Guo, Jian Liu Using the CRISPR-Cas9 system to perform base substitutions at the target site is a typical technique for genome editing with the potential for applications in gene therapy and agricultural productivity. When the CRISPR-Cas9 system uses guide RNA to direct the Cas9 endonuclease to the target site, it may misdirect it to a potential off-target site, resulting in an unintended genome editing. Although several computational methods have been proposed to predict off-target effects, there is still room for improvement in the off-target effect prediction capability. In this paper, we present an...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Jialiang Sun Source Type: research

Unlocking ensemble ecosystem modelling for large and complex networks
We present a novel sequential Monte Carlo sampling approach for ensemble generation that is orders of magnitude faster than existing approaches. We demonstrate that the methods produce equivalent parameter inferences, model predictions, and tightly constrained parameter combinations using a novel sensitivity analysis method. For one case study, we demonstrate a speed-up from 108 days to 6 hours, while maintaining equivalent ensembles. Additionally, we demonstrate how to identify the parameter combinations that strongly drive feasibility and stability, drawing ecological insight from the ensembles. Now, for the first time, ...
Source: PLoS Computational Biology - March 14, 2024 Category: Biology Authors: Sarah A. Vollert Source Type: research