Method for cycle detection in sparse, irregularly sampled, long-term neuro-behavioral timeseries: Basis pursuit denoising with polynomial detrending of long-term, inter-ictal epileptiform activity
by Irena Balzekas, Joshua Trzasko, Grace Yu, Thomas J. Richner, Filip Mivalt, Vladimir Sladky, Nicholas M. Gregg, Jamie Van Gompel, Kai Miller, Paul E. Croarkin, Vaclav Kremen, Gregory A. Worrell
Numerous physiological processes are cyclical, but sampling these processes densely enough to perform frequency decomposition and subsequent analyses can be challenging. Mathematical approaches for decomposition and reconstruction of sparsely and irregularly sampled signals are well established but have been under-utilized in physiological applications. We developed a basis pursuit denoising with polynomial detrending (BPWP) mode...
Source: PLoS Computational Biology - April 25, 2024 Category: Biology Authors: Irena Balzekas Source Type: research
Emergent neural dynamics and geometry for generalization in a transitive inference task
by Kenneth Kay, Natalie Biderman, Ramin Khajeh, Manuel Beiran, Christopher J. Cueva, Daphna Shohamy, Greg Jensen, Xue-Xin Wei, Vincent P. Ferrera, LF Abbott
Relational cognition —the ability to infer relationships that generalize to novel combinations of objects—is fundamental to human and animal intelligence. Despite this importance, it remains unclear how relational cognition is implemented in the brain due in part to a lack of hypotheses and predictions at the levels of collective neural activity and behavior. Here we discovered, analyzed, and experimentally tested neural networks (NNs) that perform transitive infe...
Source: PLoS Computational Biology - April 25, 2024 Category: Biology Authors: Kenneth Kay Source Type: research
Indirect reciprocity with Bayesian reasoning and biases
by Bryce Morsky, Joshua B. Plotkin, Erol Ak çay
Reputations can foster cooperation by indirect reciprocity: if I am good to you then others will be good to me. But this mechanism for cooperation in one-shot interactions only works when people agree on who is good and who is bad. Errors in actions or assessments can produce disagreements about reputations, which can unravel the positive feedback loop between social standing and pro-social behaviour. Cooperators can end up punished and defectors rewarded. Public reputation systems and empathy are two possible mechanisms to promote agreement about reputations. Here we sugge...
Source: PLoS Computational Biology - April 25, 2024 Category: Biology Authors: Bryce Morsky Source Type: research
A weak coupling mechanism for the early steps of the recovery stroke of myosin VI: A free energy simulation and string method analysis
by Florian E. C. Blanc, Anne Houdusse, Marco Cecchini
Myosin motors use the energy of ATP to produce force and directed movement on actin by a swing of the lever arm. ATP is hydrolysed during the off-actin re-priming transition termed recovery stroke. To provide an understanding of chemo-mechanical transduction by myosin, it is critical to determine how the reverse swing of the lever arm and ATP hydrolysis are coupled. Previous studies concluded that the recovery stroke of myosin II is initiated by closure of the Switch II loop in the nucleotide-binding site. Recently, we proposed that the recovery stroke of myosin VI sta...
Source: PLoS Computational Biology - April 25, 2024 Category: Biology Authors: Florian E. C. Blanc Source Type: research
Evolutionary analyses of intrinsically disordered regions reveal widespread signals of conservation
by Marc D. Singleton, Michael B. Eisen
Intrinsically disordered regions (IDRs) are segments of proteins without stable three-dimensional structures. As this flexibility allows them to interact with diverse binding partners, IDRs play key roles in cell signaling and gene expression. Despite the prevalence and importance of IDRs in eukaryotic proteomes and various biological processes, associating them with specific molecular functions remains a significant challenge due to their high rates of sequence evolution. However, by comparing the observed values of various IDR-associated properties against those generated under a s...
Source: PLoS Computational Biology - April 25, 2024 Category: Biology Authors: Marc D. Singleton Source Type: research
MCell4 with BioNetGen: A Monte Carlo simulator of rule-based reaction-diffusion systems with Python interface
We describe and validate a new version of the open-source MCell simulation program (MCell4), which supports generalized 3D Monte Carlo modeling of diffusion and chemical reaction of discrete molecules and macromolecular complexes in solution, on surfaces representing membranes, and combinations thereof. The main improvements in MCell4 compared to the previous versions, MCell3 and MCell3-R, include a Python interface and native BioNetGen reaction language (BNGL) support. MCell4 ’s Python interface opens up completely new possibilities for interfacing with external simulators to allow creation of sophisticated event-driven...
Source: PLoS Computational Biology - April 24, 2024 Category: Biology Authors: Adam Husar Source Type: research
A phylogenetic method linking nucleotide substitution rates to rates of continuous trait evolution
We present a phylogenetic method, PhyloAcc-C, that associates nucleotide substitution rates with changes in a continuous trait of interest. The method takes as input a multiple sequence alignment of conserved elements, continuous trait data observed in extant species, and a background phylogeny and substitution process. Gibbs sampling is used to assign rate categories (background, conserved, accelerated) to lineages and explore whether the assigned rate categories are associated with increases or decreases in the rate of trait evolution. We test our method using simulations and then illustrate its application using mammali...
Source: PLoS Computational Biology - April 24, 2024 Category: Biology Authors: Patrick Gemmell Source Type: research
Validity conditions of approximations for a target-mediated drug disposition model: A novel first-order approximation and its comparison to other approximations
by Jong Hyuk Byun, Hye Seon Jeon, Hwi-yeol Yun, Jae Kyoung Kim
Target-mediated drug disposition (TMDD) is a phenomenon characterized by a drug ’s high-affinity binding to a target molecule, which significantly influences its pharmacokinetic profile within an organism. The comprehensive TMDD model delineates this interaction, yet it may become overly complex and computationally demanding in the absence of specific concentration data for t he target or its complexes. Consequently, simplified TMDD models employing quasi-steady state approximations (QSSAs) have been introduced; however, the precise conditions under which th...
Source: PLoS Computational Biology - April 24, 2024 Category: Biology Authors: Jong Hyuk Byun Source Type: research
HGCLAMIR: Hypergraph contrastive learning with attention mechanism and integrated multi-view representation for predicting miRNA-disease associations
by Dong Ouyang, Yong Liang, Jinfeng Wang, Le Li, Ning Ai, Junning Feng, Shanghui Lu, Shuilin Liao, Xiaoying Liu, Shengli Xie
Existing studies have shown that the abnormal expression of microRNAs (miRNAs) usually leads to the occurrence and development of human diseases. Identifying disease-related miRNAs contributes to studying the pathogenesis of diseases at the molecular level. As traditional biological experiments are time-consuming and expensive, computational methods have been used as an effective complement to infer the potential associations between miRNAs and diseases. However, most of the existing computational m...
Source: PLoS Computational Biology - April 23, 2024 Category: Biology Authors: Dong Ouyang Source Type: research
Locations and structures of influenza A virus packaging-associated signals and other functional elements via an < i > in silico < /i > pipeline for predicting constrained features in RNA viruses
by Emma Beniston, Jordan P. Skittrall
Influenza A virus contains regions of its segmented genome associated with ability to package the segments into virions, but many such regions are poorly characterised. We provide detailed predictions of the key locations within these packaging-associated regions, and their structures, by applying a recently-improved pipeline for delineating constrained regions in RNA viruses and applying structural prediction algorithms. We find and characterise other known constrained regions within influenza A genomes, including the region associated with the PA-X frameshift, regions associated wit...
Source: PLoS Computational Biology - April 22, 2024 Category: Biology Authors: Emma Beniston Source Type: research
Temperature-driven coordination of circadian transcriptional regulation
We report that the phase differences between cycling genes increase as a function of geodesic distance in the low temperature condition, suggesting increased coordination of cycling on the gene regulatory network. Our results suggest a potential mechanism whereby the circadian clock mediates the fly ’s response to seasonal changes in temperature. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 22, 2024 Category: Biology Authors: Bingxian Xu Source Type: research
Neutral competition explains the clonal composition of neural organoids
by Florian G. Pflug, Simon Haendeler, Christopher Esk, Dominik Lindenhofer, J ürgen A. Knoblich, Arndt von Haeseler
Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To explain this variability, we in...
Source: PLoS Computational Biology - April 22, 2024 Category: Biology Authors: Florian G. Pflug Source Type: research
What does the mean mean? A simple test for neuroscience
by Alejandro Tlaie, Katharine Shapcott, Thijs L. van der Plas, James Rowland, Robert Lees, Joshua Keeling, Adam Packer, Paul Tiesinga, Marieke L. Sch ölvinck, Martha N. Havenith
Trial-averaged metrics, e.g. tuning curves or population response vectors, are a ubiquitous way of characterizing neuronal activity. But how relevant are such trial-averaged responses to neuronal computation itself? Here we present a simple test to estimate whether average responses reflect aspects of neuronal activity that contribute to neuronal processing. The test probes two assumptions implicitly made whenever average metrics are treated as m...
Source: PLoS Computational Biology - April 19, 2024 Category: Biology Authors: Alejandro Tlaie Source Type: research
Ranking of cell clusters in a single-cell RNA-sequencing analysis framework using prior knowledge
by Anastasis Oulas, Kyriaki Savva, Nestoras Karathanasis, George M. Spyrou
Prioritization or ranking of different cell types in a Single-cell RNA Sequencing (scRNA-Seq) framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell types and conditions in the experiment or, iii) prioritizing cell types based on prior knowledge about the conditions under study (i.e., a specific disease). These methods have drawbacks and limitations th...
Source: PLoS Computational Biology - April 18, 2024 Category: Biology Authors: Anastasis Oulas Source Type: research
Mathematical analysis of left ventricular elastance with respect to afterload change during ejection phase
by Shiro Kato, Yukiko Himeno, Akira Amano
Since the left ventricle (LV) has pressure (Plv) and volume (Vlv), we can define LV elastance from the ratio betweenPlv andVlv, termed as “instantaneous elastance.” On the other hand, end-systolic elastance (Emax) is known to be a good index of LV contractility, which is measured by the slope of several end-systolicPlv—Vlv points obtained by using different loads. The wordEmax originates from the assumption that LV elastance increases during the ejection phase and attains its maximum at the end-systole. From this concept, we can define another elastance determined by the slo...
Source: PLoS Computational Biology - April 18, 2024 Category: Biology Authors: Shiro Kato Source Type: research
