The role of cryptic ancestral symmetry in histone folding mechanisms across Eukarya and Archaea
by Haiqing Zhao, Hao Wu, Alex Guseman, Dulith Abeykoon, Christina M. Camara, Yamini Dalal, David Fushman, Garegin A. Papoian Histones compact and store DNA in both Eukarya and Archaea, forming heterodimers in Eukarya and homodimers in Archaea. Despite this, the folding mechanism of histones across species remains unclear. Our study addresses this gap by investigating 11 types of histone and histone-like proteins across humans, Drosophila, and Archaea through multiscale molecular dynamics (MD) simulations, complemented by NMR and circular dichroism experiments. We confirm and elaborate on the widely applied “folding upon...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Haiqing Zhao Source Type: research

Differences in boundary behavior in the 3D vertex and Voronoi models
by Elizabeth Lawson-Keister, Tao Zhang, Fatemeh Nazari, Fran çois Fagotto, M. Lisa Manning An important open question in the modeling of biological tissues is how to identify the right scale for coarse-graining, or equivalently, the right number of degrees of freedom. For confluent biological tissues, both vertex and Voronoi models, which differ only in their representation of the degrees of freedom, have effectively been used to predict behavior, including fluid-solid transitions and cell tissue compartmentalization, which are important for biological function. However, recent work in 2D has hinted that there may be dif...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Elizabeth Lawson-Keister Source Type: research

Explaining the flaws in human random generation as local sampling with momentum
by Lucas Castillo, Pablo Le ón-Villagrá, Nick Chater, Adam Sanborn In many tasks, human behavior is far noisier than is optimal. Yet when asked to behave randomly, people are typically too predictable. We argue that these apparently contrasting observations have the same origin: the operation of a general-purpose local sampling algorithm for probabilistic inference. This account makes distinctive predictions regarding random sequence generation, not predicted by previous accounts —which suggests that randomness is produced by inhibition of habitual behavior, striving for unpredictability. We verify these predictions i...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Lucas Castillo Source Type: research

Genome replication in asynchronously growing microbial populations
by Florian G. Pflug, Deepak Bhat, Simone Pigolotti Biological cells replicate their genomes in a well-planned manner. The DNA replication program of an organism determines the timing at which different genomic regions are replicated, with fundamental consequences for cell homeostasis and genome stability. In a growing cell culture, genomic regions that are replicated early should be more abundant than regions that are replicated late. This abundance pattern can be experimentally measured using deep sequencing. However, a general quantitative theory linking this pattern to the replication program is still lacking. In this ...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Florian G. Pflug Source Type: research

Detecting shifts in nonlinear dynamics using Empirical Dynamic Modeling with Nested-Library Analysis
by Yong-Jin Huang, Chun-Wei Chang, Chih-hao Hsieh Abrupt changes in system states and dynamical behaviors are often observed in natural systems; such phenomena, named regime shifts, are explained as transitions between alternative steady states (more generally, attractors). Various methods have been proposed to detect regime shifts from time series data, but a generic detection method with theoretical linkage to underlying dynamics is lacking. Here, we provide a novel method named Nested-Library Analysis (NLA) to retrospectively detect regime shifts using empirical dynamic modeling (EDM) rooted in theory of attractor reco...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Yong-Jin Huang Source Type: research

Landscape quantifies the intermediate state and transition dynamics in ecological networks
by Jinchao Lv, Jin Wang, Chunhe Li Understanding the ecological mechanisms associated with the collapse and restoration is especially critical in promoting harmonious coexistence between humans and nature. So far, it remains challenging to elucidate the mechanisms of stochastic dynamical transitions for ecological systems. Using an example of plant-pollinator network, we quantified the energy landscape of ecological system. The landscape displays multiple attractors characterizing the high, low and intermediate abundance stable states. Interestingly, we detected the intermediate states under pollinator decline, and demons...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Jinchao Lv Source Type: research

sc2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data
by Jiarui Feng, S. Peter Goedegebuure, Amanda Zeng, Ye Bi, Ting Wang, Philip Payne, Li Ding, David DeNardo, William Hawkins, Ryan C. Fields, Fuhai Li Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer ’s Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to i...
Source: PLoS Computational Biology - January 5, 2024 Category: Biology Authors: Jiarui Feng Source Type: research

Wildlife vaccination strategies for eliminating bovine tuberculosis in white-tailed deer populations
by Aakash Pandey, Abigail B. Feuka, Melinda Cosgrove, Megan Moriarty, Anthony Duffiney, Kurt C. VerCauteren, Henry Campa III, Kim M. Pepin Many pathogens of humans and livestock also infect wildlife that can act as a reservoir and challenge disease control or elimination. Efficient and effective prioritization of research and management actions requires an understanding of the potential for new tools to improve elimination probability with feasible deployment strategies that can be implemented at scale. Wildlife vaccination is gaining interest as a tool for managing several wildlife diseases. To evaluate the effect of vac...
Source: PLoS Computational Biology - January 4, 2024 Category: Biology Authors: Aakash Pandey Source Type: research

Harnessing the flexibility of neural networks to predict dynamic theoretical parameters underlying human choice behavior
by Yoav Ger, Eliya Nachmani, Lior Wolf, Nitzan Shahar Reinforcement learning (RL) models are used extensively to study human behavior. These rely on normative models of behavior and stress interpretability over predictive capabilities. More recently, neural network models have emerged as a descriptive modeling paradigm that is capable of high predictive power yet with limited interpretability. Here, we seek to augment the expressiveness of theoretical RL models with the high flexibility and predictive power of neural networks. We introduce a novel framework, which we term theoretical-RNN (t-RNN), whereby a recurrent neura...
Source: PLoS Computational Biology - January 4, 2024 Category: Biology Authors: Yoav Ger Source Type: research

Quantifying the distribution of feature values over data represented in arbitrary dimensional spaces
by Enrique R. Sebastian, Julio Esparza, Liset M. de la Prida Identifying the structured distribution (or lack thereof) of a given feature over a point cloud is a general research question. In the neuroscience field, this problem arises while investigating representations over neural manifolds (e.g., spatial coding), in the analysis of neurophysiological signals (e.g., sensory coding) or in anatomical image segmentation. We introduce the Structure Index (SI) as a directed graph-based metric to quantify the distribution of feature values projected over data in arbitrary D-dimensional spaces (defined from neurons, time stamp...
Source: PLoS Computational Biology - January 4, 2024 Category: Biology Authors: Enrique R. Sebastian Source Type: research

The spinal cord facilitates cerebellar upper limb motor learning and control; inputs from neuromusculoskeletal simulation
by Alice Bruel, Ignacio Abad ía, Thibault Collin, Icare Sakr, Henri Lorach, Niceto R. Luque, Eduardo Ros, Auke Ijspeert Complex interactions between brain regions and the spinal cord (SC) govern body motion, which is ultimately driven by muscle activation. Motor planning or learning are mainly conducted at higher brain regions, whilst the SC acts as a brain-muscle gateway and as a motor control centre providing fast reflexes and muscle activity regulation. Thus, higher brain areas need to cope with the SC as an inherent and evolutionary older part of the body dynamics. Here, we address the question of how SC dynamics aff...
Source: PLoS Computational Biology - January 2, 2024 Category: Biology Authors: Alice Bruel Source Type: research

Recurrence risk stratification of hepatocellular carcinomas based on immune gene expression and features extracted from pathological images
by Tao Ding, Xiao Li, Jiu Mo, Gregory Alexander, Jialu Li BackgroundImmune-based therapy is a promising type of treatment for hepatocellular carcinoma (HCC) but has only been partially successful due to the high heterogeneity in HCC tumor. The differences in the degree of tumor cell progression and in the activity of tumor immune microenvironment could lead to varied clinical outcome. Accurate subgrouping for recurrence risk is an approach to address the issue of such heterogeneity. It remains under investigation as whether integrating quantitative whole slide image (WSI) features with the expression profile of immune mark...
Source: PLoS Computational Biology - December 29, 2023 Category: Biology Authors: Tao Ding Source Type: research

Pneumococcal population dynamics: Investigating vaccine-induced changes through multiscale modelling
by Nicola Mulberry, Alexander R. Rutherford, Caroline Colijn The mechanisms behind vaccine-induced strain replacement in the pneumococcus remain poorly understood. There is emerging evidence that distinct pneumococcal lineages can co-colonise for significant time periods, and that novel recombinants can readily emerge during natural colonisation. Despite this, patterns of post-vaccine replacement are indicative of competition between specific lineages. Here, we develop a multiscale transmission model to investigate explicitly how within host dynamics shape observed ecological patterns, both pre- and post-vaccination. Our ...
Source: PLoS Computational Biology - December 28, 2023 Category: Biology Authors: Nicola Mulberry Source Type: research

A computational model of < i > Pseudomonas syringae < /i > metabolism unveils a role for branched-chain amino acids in Arabidopsis leaf colonization
by Philip J. Tubergen, Greg Medlock, Anni Moore, Xiaomu Zhang, Jason A. Papin, Cristian H. Danna Bacterial pathogens adapt their metabolism to the plant environment to successfully colonize their hosts. In our efforts to uncover the metabolic pathways that contribute to the colonization ofArabidopsis thaliana leaves byPseudomonas syringae pvtomato DC3000 (Pst DC3000), we created iPst19, an ensemble of 100 genome-scale network reconstructions ofPst DC3000 metabolism. We developed a novel approach for gene essentiality screens, leveraging the predictive power of iPst19 to identify core and ancillary condition-specific essen...
Source: PLoS Computational Biology - December 27, 2023 Category: Biology Authors: Philip J. Tubergen Source Type: research

Normalization by orientation-tuned surround in human V1-V3
by Zeming Fang, Ilona M. Bloem, Catherine Olsson, Wei Ji Ma, Jonathan Winawer An influential account of neuronal responses in primary visual cortex is the normalized energy model. This model is often implemented as a multi-stage computation. The first stage is linear filtering. The second stage is the extraction of contrast energy, whereby a complex cell computes the squared and summed outputs of a pair of the linear filters in quadrature phase. The third stage is normalization, in which a local population of complex cells mutually inhibit one another. Because the population includes cells tuned to a range of orientations...
Source: PLoS Computational Biology - December 27, 2023 Category: Biology Authors: Zeming Fang Source Type: research