@article{21115, abstract = {Quantifying cell morphology is central to understanding cellular regulation, fate, and heterogeneity, yet conventional image-based analyses often struggle with diverse or irregular shapes. We present a computational framework that uses topological data analysis to characterise and compare single-cell morphologies from fluorescence microscopy. Each cell is represented by its contour together with the position of its nucleus, from which we construct a filtration based on a radial distance function and derive a persistence diagram encoding the shape’s topological evolution. The similarity between two cells is quantified using the 2-Wasserstein distance between their diagrams, yielding a shape distance we call the PH distance. We apply this method to two representative experimental systems—primary human mesenchymal stem cells (hMSCs) and HeLa cells—and show that PH distances enable the detection of outliers in those systems, the identification of sub-populations, and the quantification of shape heterogeneity. We benchmark PH against three established contour-based distances (aspect ratio, Fourier descriptors, and elastic shape analysis) and show that PH offers better separation between cell types and greater robustness when clustering heterogeneous populations. Together, these results demonstrate that persistent-homology-based signatures provide a principled and sensitive approach for analysing cell morphology in settings where traditional geometric or image-based descriptors are insufficient.}, author = {Bleile, Yossi and Yadav, Pooja and Koehl, Patrice and Rehfeldt, Florian}, issn = {1553-7358}, journal = {PLoS Computational Biology}, publisher = {Public Library of Science}, title = {{Persistence diagrams as morphological signatures of cells: A method to measure and compare cells within a population}}, doi = {10.1371/journal.pcbi.1013890}, volume = {22}, year = {2026}, } @article{15258, abstract = {Inclusion at academic events is facing increased scrutiny as the communities these events serve raise their expectations for who can practically attend. Active efforts in recent years to bring more diversity to academic events have brought progress and created momentum. However, we must reflect on these efforts and determine which underrepresented groups are being disadvantaged. Inclusion at academic events is important to ensure diversity of discourse and opinion, to help build networks, and to avoid academic siloing. All of these contribute to the development of a robust and resilient academic field. We have developed these Ten Simple Rules both to amplify the voices that have been speaking out and to celebrate the progress of many Equity, Diversity, and Inclusivity practices that continue to drive the organisation of academic events. The Rules aim to raise awareness as well as provide actionable suggestions and tools to support these initiatives further. This aims to support academic organisations such as the Deep Learning Indaba, Neuromatch Academy, the IBRO-Simons Computational Neuroscience Imbizo, Biodiversity Information Standards (TDWG), Arabs in Neuroscience, FAIRPoints, and OLS (formerly Open Life Science). This article is a call to action for organisers to reevaluate the impact and reach of their inclusive practices.}, author = {Hall, Siobhan Mackenzie and Kochin, Daniel and Carne, Carmel and Herterich, Patricia and Lewers, Kristen Lenay and Abdelhack, Mohamed and Ramasubramanian, Arun and Michael Alphonse, Juno Felecia and Ung, Visotheary and El-Gebali, Sara and Currin, Christopher and Plomp, Esther and Thompson, Rachel and Sharan, Malvika}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {3}, publisher = {Public Library of Science}, title = {{Ten simple rules for pushing boundaries of inclusion at academic events}}, doi = {10.1371/journal.pcbi.1011797}, volume = {20}, year = {2024}, } @article{12152, abstract = {ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks.}, author = {Jiang, Xiuyun and Harker-Kirschneck, Lena and Vanhille-Campos, Christian Eduardo and Pfitzner, Anna-Katharina and Lominadze, Elene and Roux, Aurélien and Baum, Buzz and Šarić, Anđela}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics}, number = {10}, publisher = {Public Library of Science}, title = {{Modelling membrane reshaping by staged polymerization of ESCRT-III filaments}}, doi = {10.1371/journal.pcbi.1010586}, volume = {18}, year = {2022}, } @article{8997, abstract = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions}, publisher = {Public Library of Science}, title = {{Minimal biophysical model of combined antibiotic action}}, doi = {10.1371/journal.pcbi.1008529}, volume = {17}, year = {2021}, } @article{17132, abstract = {Extracellular recording is an accessible technique used in animals and humans to study the brain physiology and pathology. As the number of recording channels and their density grows it is natural to ask how much improvement the additional channels bring in and how we can optimally use the new capabilities for monitoring the brain. Here we show that for any given distribution of electrodes we can establish exactly what information about current sources in the brain can be recovered and what information is strictly unobservable. We demonstrate this in the general setting of previously proposed kernel Current Source Density method and illustrate it with simplified examples as well as using evoked potentials from the barrel cortex obtained with a Neuropixels probe and with compatible model data. We show that with conceptual separation of the estimation space from experimental setup one can recover sources not accessible to standard methods.}, author = {Chintaluri, Chaitanya and Bejtka, Marta and Średniawa, Władysław and Czerwiński, Michał and Dzik, Jakub M. and Jędrzejewska-Szmek, Joanna and Kondrakiewicz, Kacper and Kublik, Ewa and Wójcik, Daniel K.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {5}, publisher = {Public Library of Science}, title = {{What we can and what we cannot see with extracellular multielectrodes}}, doi = {10.1371/journal.pcbi.1008615}, volume = {17}, year = {2021}, } @article{7569, abstract = {Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.}, author = {Grah, Rok and Friedlander, Tamar}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {2}, publisher = {Public Library of Science}, title = {{The relation between crosstalk and gene regulation form revisited}}, doi = {10.1371/journal.pcbi.1007642}, volume = {16}, year = {2020}, } @article{8013, author = {Currin, Christopher B. and Khoza, Phumlani N. and Antrobus, Alexander D. and Latham, Peter E. and Vogels, Tim P and Raimondo, Joseph V.}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {7}, publisher = {Public Library of Science}, title = {{Think: Theory for Africa}}, doi = {10.1371/journal.pcbi.1007049}, volume = {15}, year = {2019}, } @article{7103, abstract = {Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.}, author = {Wang, Jilin W. J. L. and Lombardi, Fabrizio and Zhang, Xiyun and Anaclet, Christelle and Ivanov, Plamen Ch.}, issn = {1553-7358}, journal = {PLoS Computational Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture}}, doi = {10.1371/journal.pcbi.1007268}, volume = {15}, year = {2019}, }