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
Non-invasive assessment of stroke volume and cardiovascular parameters based on peripheral pressure waveform
by Kamil Wo łos, Leszek Pstras, Malgorzata Debowska, Wojciech Dabrowski, Dorota Siwicka-Gieroba, Jan Poleszczuk
Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters describing the selected properties of the cardiovascular system. Peripheral pressure waveforms were recorded in the radial artery using applanation tonometry (Sphygm...
Source: PLoS Computational Biology - April 18, 2024 Category: Biology Authors: Kamil Wo łos Source Type: research
Precise cortical contributions to sensorimotor feedback control during reactive balance
by Scott Boebinger, Aiden Payne, Giovanni Martino, Kennedy Kerr, Jasmine Mirdamadi, J. Lucas McKay, Michael Borich, Lena Ting
The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships betw...
Source: PLoS Computational Biology - April 17, 2024 Category: Biology Authors: Scott Boebinger Source Type: research
Encoding surprise by retinal ganglion cells
by Danica Despotovi ć, Corentin Joffrois, Olivier Marre, Matthew Chalk
The efficient coding hypothesis posits that early sensory neurons transmit maximal information about sensory stimuli, given internal constraints. A central prediction of this theory is that neurons should preferentially encode stimuli that are most surprising. Previous studies suggest this may be the case in early visual areas, where many neurons respond strongly to rare or surprising stimuli. For example, previous research showed that when presented with a rhythmic sequence of full-field flashes, many retinal ganglion cells (RGCs) respond strongly at...
Source: PLoS Computational Biology - April 17, 2024 Category: Biology Authors: Danica Despotovi ć Source Type: research
CoVar: A generalizable machine learning approach to identify the coordinated regulators driving variational gene expression
We present CoVar, an ML-based framework that builds upon the properties of existing inference models, to find the central genes driving perturbed gene expression across biological states. Unlike differentially expressed genes (DEGs) that capture changes in individual gene expression across conditions, CoVar focuses on identifyingvariational genes that undergo changes in their expression network interaction profiles, providing insights into changes in the regulatory dynamics, such as in disease pathogenesis. Subsequently, it findscore genes from among the nearest neighbors of these variational genes, which are central to th...
Source: PLoS Computational Biology - April 17, 2024 Category: Biology Authors: Satyaki Roy Source Type: research
How robust are estimates of key parameters in standard viral dynamic models?
by Carolin Zitzmann, Ruian Ke, Ruy M. Ribeiro, Alan S. Perelson
Mathematical models of viral infection have been developed, fitted to data, and provide insight into disease pathogenesis for multiple agents that cause chronic infection, including HIV, hepatitis C, and B virus. However, for agents that cause acute infections or during the acute stage of agents that cause chronic infections, viral load data are often collected after symptoms develop, usually around or after the peak viral load. Consequently, we frequently lack data in the initial phase of viral growth, i.e., when pre-symptomatic transmission events occur. Mi...
Source: PLoS Computational Biology - April 16, 2024 Category: Biology Authors: Carolin Zitzmann Source Type: research
Network-neuron interactions underlying sensory responses of layer 5 pyramidal tract neurons in barrel cortex
by Arco Bast, Rieke Fruengel, Christiaan P. J. de Kock, Marcel Oberlaender
Neurons in the cerebral cortex receive thousands of synaptic inputs per second from thousands of presynaptic neurons. How the dendritic location of inputs, their timing, strength, and presynaptic origin, in conjunction with complex dendritic physiology, impact the transformation of synaptic input into action potential (AP) output remains generally unknown forin vivo conditions. Here, we introduce a computational approach to reveal which properties of the input causally underlie AP output, and how this neuronal input-output computation is influenced...
Source: PLoS Computational Biology - April 16, 2024 Category: Biology Authors: Arco Bast Source Type: research
Dopamine encoding of novelty facilitates efficient uncertainty-driven exploration
by Yuhao Wang, Armin Lak, Sanjay G. Manohar, Rafal Bogacz
When facing an unfamiliar environment, animals need to explore to gain new knowledge about which actions provide reward, but also put the newly acquired knowledge to use as quickly as possible. Optimal reinforcement learning strategies should therefore assess the uncertainties of these action –reward associations and utilise them to inform decision making. We propose a novel model whereby direct and indirect striatal pathways act together to estimate both the mean and variance of reward distributions, and mesolimbic dopaminergic neurons provide transient novelty ...
Source: PLoS Computational Biology - April 16, 2024 Category: Biology Authors: Yuhao Wang Source Type: research
Gradient boosted decision trees reveal nuances of auditory discrimination behavior
by Carla S. Griffiths, Jules M. Lebert, Joseph Sollini, Jennifer K. Bizley
Animal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target word ’s presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals’ ability to generalize across pitch, we manipulated the fundamental fre...
Source: PLoS Computational Biology - April 16, 2024 Category: Biology Authors: Carla S. Griffiths Source Type: research
