Mutational signature dynamics indicate SARS-CoV-2 ’s evolutionary capacity is driven by host antiviral molecules
by Kieran D. Lamb, Martha M. Luka, Megan Saathoff, Richard J. Orton, My V. T. Phan, Matthew Cotten, Ke Yuan, David L. Robertson
The COVID-19 pandemic has been characterised by sequential variant-specific waves shaped by viral, individual human and population factors. SARS-CoV-2 variants are defined by their unique combinations of mutations and there has been a clear adaptation to more efficient human infection since the emergence of this new human coronavirus in late 2019. Here, we use machine learning models to identify shared signatures, i.e., common underlying mutational processes and link these to the subset of mutati...
Source: PLoS Computational Biology - January 25, 2024 Category: Biology Authors: Kieran D. Lamb Source Type: research
Inferring country-specific import risk of diseases from the world air transportation network
by Pascal P. Klamser, Adrian Zachariae, Benjamin F. Maier, Olga Baranov, Clara Jongen, Frank Schlosser, Dirk Brockmann
Disease propagation between countries strongly depends on their effective distance, a measure derived from the world air transportation network (WAN). It reduces the complex spreading patterns of a pandemic to a wave-like propagation from the outbreak country, establishing a linear relationship to the arrival time of the unmitigated spread of a disease. However, in the early stages of an outbreak, what concerns decision-makers in countries is understanding the relative risk of active cases arriving in the...
Source: PLoS Computational Biology - January 24, 2024 Category: Biology Authors: Pascal P. Klamser Source Type: research
Chromatin phase separated nanoregions explored by polymer cross-linker models and reconstructed from single particle trajectories
by Andrea Papale, David Holcman
Phase separated domains (PSDs) are ubiquitous in cell biology, representing nanoregions of high molecular concentration. PSDs appear at diverse cellular domains, such as neuronal synapses but also in eukaryotic cell nucleus, limiting the access of transcription factors and thus preventing gene expression. We develop a generalized cross-linker polymer model, to study PSDs: we show that increasing the number of cross-linkers induces a polymer condensation, preventing access of diffusing molecules. To investigate how the PSDs restrict the motion of diffusing molecules, we compute the mean resi...
Source: PLoS Computational Biology - January 24, 2024 Category: Biology Authors: Andrea Papale Source Type: research
A genome-wide comprehensive analysis of nucleosome positioning in yeast
by Leo Zeitler, K évin André, Adriana Alberti, Cyril Denby Wilkes, Julie Soutourina, Arach Goldar
In eukaryotic cells, the one-dimensional DNA molecules need to be tightly packaged into the spatially constraining nucleus. Folding is achieved on its lowest level by wrapping the DNA around nucleosomes. Their arrangement regulates other nuclear processes, such as transcription and DNA repair. Despite strong efforts to study nucleosome positioning using Next Generation Sequencing (NGS) data, the mechanism of their collective arrangement along the gene body remains poorly understood. Here, we classify nucleosome distribution...
Source: PLoS Computational Biology - January 24, 2024 Category: Biology Authors: Leo Zeitler Source Type: research
Examining B-cell dynamics and responsiveness in different inflammatory milieus using an agent-based model
ConclusionThe BCIABM proved useful in dynamically representing known mechanisms of B-cell function and reproduced immune memory responses across a range of different antigen exposures and inflammatory statuses. These results elucidate previous studies demonstrating a similar negative correlation between the B-cell response and background inflammation by positing an established and conserved mechanism that explains B-cell dysfunction across a wide range of phenotypic presentations. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - January 23, 2024 Category: Biology Authors: Bryan Shin Source Type: research
Implicit model to capture electrostatic features of membrane environment
by Rituparna Samanta, Jeffrey J. Gray
Membrane protein structure prediction and design are challenging due to the complexity of capturing the interactions in the lipid layer, such as those arising from electrostatics. Accurately capturing electrostatic energies in the low-dielectric membrane often requires expensive Poisson-Boltzmann calculations that are not scalable for membrane protein structure prediction and design. In this work, we have developed a fast-to-compute implicit energy function that considers the realistic characteristics of different lipid bilayers, making design calculations tractable. This method captu...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Rituparna Samanta Source Type: research
FindAdapt: A python package for fast and accurate adapter detection in small RNA sequencing
by Hua-Chang Chen, Jing Wang, Yu Shyr, Qi Liu
Adapter trimming is an essential step for analyzing small RNA sequencing data, where reads are generally longer than target RNAs ranging from 18 to 30 bp. Most adapter trimming tools require adapter information as input. However, adapter information is hard to access, specified incorrectly, or not provided with publicly available datasets, hampering their reproducibility and reusability. Manual identification of adapter patterns from raw reads is labor-intensive and error-prone. Moreover, the use of randomized adapters to reduce ligation biases during library preparation makes...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Hua-Chang Chen Source Type: research
Predicting primate tongue morphology based on geometrical skull matching. A first step towards an application on fossil hominins
by Pablo Alvarez, Marouane El Mouss, Maxime Calka, Anca Belme, Gilles Berillon, Pauline Brige, Yohan Payan, Pascal Perrier, Am élie Vialet
As part of a long-term research project aiming at generating a biomechanical model of a fossil human tongue from a carefully designed 3D Finite Element mesh of a living human tongue, we present a computer-based method that optimally registers 3D CT images of the head and neck of the living human into similar images of another primate. We quantitatively evaluate the method on a baboon. The method generates a geometric deformation field which is used to build up a 3D Finite Element mesh...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Pablo Alvarez Source Type: research
< i > Regulus < /i > infers signed regulatory relations from few samples ’ information using discretization and likelihood constraints
by Marine Louarn, Guillaume Collet, Ève Barré, Thierry Fest, Olivier Dameron, Anne Siegel, Fabrice Chatonnet
MotivationTranscriptional regulation is performed by transcription factors (TF) binding to DNA in context-dependent regulatory regions and determines the activation or inhibition of gene expression. Current methods of transcriptional regulatory circuits inference, based on one or all of TF, regions and genes activity measurements require a large number of samples for ranking the candidate TF-gene regulation relations and rarely predict whether they are activations or inhibitions.We hypothesize that transcriptional...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Marine Louarn Source Type: research
Inferred regulons are consistent with regulator binding sequences in < i > E < /i > . < i > coli < /i >
by Sizhe Qiu, Xinlong Wan, Yueshan Liang, Cameron Lamoureux, Amir Akbari, Bernhard O. Palsson, Daniel C. Zielinski
The transcriptional regulatory network (TRN) ofE.coli consists of thousands of interactions between regulators and DNA sequences. Regulons are typically determined either from resource-intensive experimental measurement of functional binding sites, or inferred from analysis of high-throughput gene expression datasets. Recently, independent component analysis (ICA) of RNA-seq compendia has shown to be a powerful method for inferring bacterial regulons. However, it remains unclear to what extent regulons predic...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Sizhe Qiu Source Type: research
Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation
by Javier Robles, Ananth Prakash, Juan Antonio Vizca íno, J. Ignacio Casal
The cancer biomarker field has been an object of thorough investigation in the last decades. Despite this, colorectal cancer (CRC) heterogeneity makes it challenging to identify and validate effective prognostic biomarkers for patient classification according to outcome and treatment response. Although a massive amount of proteomics data has been deposited in public data repositories, this rich source of information is vastly underused. Here, we attempted to reuse public proteomics datasets with two main objectives: i) to generate hypotheses (dete...
Source: PLoS Computational Biology - January 22, 2024 Category: Biology Authors: Javier Robles Source Type: research
Postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents: A simulation study
This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - January 19, 2024 Category: Biology Authors: Laura Schmid Source Type: research
The structure and robustness of ecological networks with two interaction types
by Virginia Dom ínguez-García, Sonia Kéfi
Until recently, most ecological network analyses investigating the effects of species ’ declines and extinctions have focused on a single type of interaction (e.g. feeding). In nature, however, diverse interactions co-occur, each of them forming a layer of a ‘multilayer’ network. Data including information on multiple interaction types has recently started to emerge, giving us the opportunity to have a first glance at possible commonalities in the structure of these networks. We studied the structural features of 44 tripartite ecological networks from the literature, each...
Source: PLoS Computational Biology - January 19, 2024 Category: Biology Authors: Virginia Dom ínguez-García Source Type: research
Identifying essential factors for energy-efficient walking control across a wide range of velocities in reflex-based musculoskeletal systems
by Shunsuke Koseki, Mitsuhiro Hayashibe, Dai Owaki
Humans can generate and sustain a wide range of walking velocities while optimizing their energy efficiency. Understanding the intricate mechanisms governing human walking will contribute to the engineering applications such as energy-efficient biped robots and walking assistive devices. Reflex-based control mechanisms, which generate motor patterns in response to sensory feedback, have shown promise in generating human-like walking in musculoskeletal models. However, the precise regulation of velocity remains a major challenge. This limitation makes it difficult to ident...
Source: PLoS Computational Biology - January 19, 2024 Category: Biology Authors: Shunsuke Koseki Source Type: research
Revealing and reshaping attractor dynamics in large networks of cortical neurons
by Chen Beer, Omri Barak
Attractors play a key role in a wide range of processes including learning and memory. Due to recent innovations in recording methods, there is increasing evidence for the existence of attractor dynamics in the brain. Yet, our understanding of how these attractors emerge or disappear in a biological system is lacking.
By following the spontaneous network bursts of cultured cortical networks, we are able to define a vocabulary of spatiotemporal patterns and show that they function as discrete attractors in the network dynamics. We show that electrically stimulating specific attractors eliminates th...
Source: PLoS Computational Biology - January 19, 2024 Category: Biology Authors: Chen Beer Source Type: research
