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Suryanarayana Maddu, Bevan Cheeseman, Christian L. Müller, Ivo F. Sbalzarini
Learning physically consistent differential equation models from data using group sparsity.
Phys Rev E, 103(4) Art. No. 042310 (2021)
  Source   

We propose a statistical learning framework based on group-sparse regression that can be used to (i) enforce conservation laws, (ii) ensure model equivalence, and (iii) guarantee symmetries when learning or inferring differential-equation models from data. Directly learning interpretable mathematical models from data has emerged as a valuable modeling approach. However, in areas such as biology, high noise levels, sensor-induced correlations, and strong intersystem variability can render data-driven models nonsensical or physically inconsistent without additional constraints on the model structure. Hence, it is important to leverage prior knowledge from physical principles to learn biologically plausible and physically consistent models rather than models that simply fit the data best. We present the group iterative hard thresholding algorithm and use stability selection to infer physically consistent models with minimal parameter tuning. We show several applications from systems biology that demonstrate the benefits of enforcing priors in data-driven modeling.
@article{Maddu8008,
author={Suryanarayana Maddu, Bevan Cheeseman, Christian L. Müller, Ivo F. Sbalzarini},
title={Learning physically consistent differential equation models from data using group sparsity.},
journal ={Physical Review E},
volume={103},
issue ={4},
pages={1--1},
year=2021
}

Stephanie Spannl, Tomasz Buhl, Ioannis Nellas, Salma A Zeidan, K Venkatesan Iyer, Helena Khaliullina, Carsten Schultz, André Nadler, Natalie Dye, Suzanne Eaton
Glycolysis regulates Hedgehog signalling via the plasma membrane potential : Erratum ; Correction to EMBO J. 39 (2020) 21: e101767
EMBO J, 40(7) Art. No. 107925 (2021)
PubMed Source  

@article{Spannl8012,
author={Stephanie Spannl, Tomasz Buhl, Ioannis Nellas, Salma A Zeidan, K Venkatesan Iyer, Helena Khaliullina, Carsten Schultz, André Nadler, Natalie Dye, Suzanne Eaton},
title={Glycolysis regulates Hedgehog signalling via the plasma membrane potential : Erratum ; Correction to EMBO J. 39 (2020) 21: e101767},
journal ={The EMBO journal},
volume={40},
issue ={7},
pages={null--null},
year=2021
}

Mark S Springer, Christian F Guerrero-Juarez, Matthias Huelsmann, Matthew A Collin, Kerri Danil, Michael R McGowen, Ji Won Oh, Raul Ramos, Michael Hiller#, Maksim V Plikus#, John Gatesy#
Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos.
Curr Biol, Art. No. doi: 10.1016/j.cub.2021.02.057 (2021)
PubMed Source   

The macroevolutionary transition from terra firma to obligatory inhabitance of the marine hydrosphere has occurred twice in the history of Mammalia: Cetacea and Sirenia. In the case of Cetacea (whales, dolphins, and porpoises), molecular phylogenies provide unambiguous evidence that fully aquatic cetaceans and semiaquatic hippopotamids (hippos) are each other's closest living relatives. Ancestral reconstructions suggest that some adaptations to the aquatic realm evolved in the common ancestor of Cetancodonta (Cetacea + Hippopotamidae). An alternative hypothesis is that these adaptations evolved independently in cetaceans and hippos. Here, we focus on the integumentary system and evaluate these hypotheses by integrating new histological data for cetaceans and hippos, the first genome-scale data for pygmy hippopotamus, and comprehensive genomic screens and molecular evolutionary analyses for protein-coding genes that have been inactivated in hippos and cetaceans. We identified eight skin-related genes that are inactivated in both cetaceans and hippos, including genes that are related to sebaceous glands, hair follicles, and epidermal differentiation. However, none of these genes exhibit inactivating mutations that are shared by cetaceans and hippos. Mean dates for the inactivation of skin genes in these two clades serve as proxies for phenotypic changes and suggest that hair reduction/loss, the loss of sebaceous glands, and changes to the keratinization program occurred ∼16 Ma earlier in cetaceans (∼46.5 Ma) than in hippos (∼30.5 Ma). These results, together with histological differences in the integument and prior analyses of oxygen isotopes from stem hippopotamids ("anthracotheres"), support the hypothesis that aquatic skin adaptations evolved independently in hippos and cetaceans.
@article{Springer8004,
author={Mark S Springer, Christian F Guerrero-Juarez, Matthias Huelsmann, Matthew A Collin, Kerri Danil, Michael R McGowen, Ji Won Oh, Raul Ramos, Michael Hiller, Maksim V Plikus, John Gatesy},
title={Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos.},
journal ={Current biology : CB},
volume={},
pages={1--1},
year=2021
}

Claudio Durán✳︎, Sara Ciucci✳︎, Alessandra Palladini✳︎, Umer Z Ijaz, Antonio Giuliano Zippo, Francesco Paroni Sterbini, Luca Masucci, Giovanni Cammarota, Gianluca Ianiro, Pirjo Spuul, Michael Schroeder, Stephan W. Grill, Bryony N Parsons, D Mark Pritchard, Brunella Posteraro, Maurizio Sanguinetti, Giovanni Gasbarrini, Antonio Gasbarrini, Carlo Vittorio Cannistraci
Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome.
Nat Commun, 12(1) Art. No. 1926 (2021)
PubMed Source   

The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.
@article{Durán7992,
author={Claudio Durán, Sara Ciucci, Alessandra Palladini, Umer Z Ijaz, Antonio Giuliano Zippo, Francesco Paroni Sterbini, Luca Masucci, Giovanni Cammarota, Gianluca Ianiro, Pirjo Spuul, Michael Schroeder, Stephan W. Grill, Bryony N Parsons, D Mark Pritchard, Brunella Posteraro, Maurizio Sanguinetti, Giovanni Gasbarrini, Antonio Gasbarrini, Carlo Vittorio Cannistraci},
title={Nonlinear machine learning pattern recognition and bacteria-metabolite multilayer network analysis of perturbed gastric microbiome.},
journal ={Nature communications},
volume={12},
issue ={1},
pages={null--null},
year=2021
}

Natalie Dye✳︎#, Marko Popovic✳︎, K Venkatesan Iyer, Jana Fuhrmann, Romina Piscitello-Gómez, Suzanne Eaton, Frank Jülicher#
Self-organized patterning of cell morphology via mechanosensitive feedback.
Elife, 10 Art. No. e57964 (2021)
PubMed Source   

Tissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in the Drosophila wing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis.
@article{Dye7993,
author={Natalie Dye, Marko Popovic, K Venkatesan Iyer, Jana Fuhrmann, Romina Piscitello-Gómez, Suzanne Eaton, Frank Jülicher},
title={Self-organized patterning of cell morphology via mechanosensitive feedback.},
journal ={eLife},
volume={10},
pages={1--1},
year=2021
}

K Venkatesan Iyer#, Anna Taubenberger, Salma A Zeidan, Natalie Dye, Suzanne Eaton, Frank Jülicher#
Apico-basal cell compression regulates Lamin A/C levels in epithelial tissues.
Nat Commun, 12(1) Art. No. 1756 (2021)
PubMed Source   

The levels of nuclear protein Lamin A/C are crucial for nuclear mechanotransduction. Lamin A/C levels are known to scale with tissue stiffness and extracellular matrix levels in mesenchymal tissues. But in epithelial tissues, where cells lack a strong interaction with the extracellular matrix, it is unclear how Lamin A/C is regulated. Here, we show in epithelial tissues that Lamin A/C levels scale with apico-basal cell compression, independent of tissue stiffness. Using genetic perturbations in Drosophila epithelial tissues, we show that apico-basal cell compression regulates the levels of Lamin A/C by deforming the nucleus. Further, in mammalian epithelial cells, we show that nuclear deformation regulates Lamin A/C levels by modulating the levels of phosphorylation of Lamin A/C at Serine 22, a target for Lamin A/C degradation. Taken together, our results reveal a mechanism of Lamin A/C regulation which could provide key insights for understanding nuclear mechanotransduction in epithelial tissues.
@article{Iyer7994,
author={K Venkatesan Iyer, Anna Taubenberger, Salma A Zeidan, Natalie Dye, Suzanne Eaton, Frank Jülicher},
title={Apico-basal cell compression regulates Lamin A/C levels in epithelial tissues.},
journal ={Nature communications},
volume={12},
issue ={1},
pages={null--null},
year=2021
}

Marta Urbanska, Annemarie Lüdecke, Wilhelm Walter, Antoine M van Oijen, Karl E Duderstadt, Stefan Diez
Highly-Parallel Microfluidics-Based Force Spectroscopy on Single Cytoskeletal Motors.
Small, Art. No. 2007388 (2021)
PubMed Source   

Cytoskeletal motors transform chemical energy into mechanical work to drive essential cellular functions. Optical trapping experiments have provided crucial insights into the operation of these molecular machines under load. However, the throughput of such force spectroscopy experiments is typically limited to one measurement at a time. Here, a highly-parallel, microfluidics-based method that allows for rapid collection of force-dependent motility parameters of cytoskeletal motors with two orders of magnitude improvement in throughput compared to currently available methods is introduced. Tunable hydrodynamic forces to stepping kinesin-1 motors via DNA-tethered beads and utilize a large field of view to simultaneously track the velocities, run lengths, and interaction times of hundreds of individual kinesin-1 molecules under varying resisting and assisting loads are applied. Importantly, the 16 µm long DNA tethers between the motors and the beads significantly reduces the vertical component of the applied force pulling the motors away from the microtubule. The approach is readily applicable to other molecular systems and constitutes a new methodology for parallelized single-molecule force studies on cytoskeletal motors.
@article{Urbanska7991,
author={Marta Urbanska, Annemarie Lüdecke, Wilhelm Walter, Antoine M van Oijen, Karl E Duderstadt, Stefan Diez},
title={Highly-Parallel Microfluidics-Based Force Spectroscopy on Single Cytoskeletal Motors.},
journal ={Small (Weinheim an der Bergstrasse, Germany)},
volume={},
pages={null--null},
year=2021
}

Georgia R Squyres, Matthew J Holmes, Sarah R Barger, Betheney R Pennycook, Joel Ryan, Victoria T Yan, Ethan C Garner
Single-molecule imaging reveals that Z-ring condensation is essential for cell division in Bacillus subtilis.
Nat Microbiol, Art. No. doi: 10.1038/s41564-021-00878-z (2021)
PubMed Source   

Although many components of the cell division machinery in bacteria have been identified1,2, the mechanisms by which they work together to divide the cell remain poorly understood. Key among these components is the tubulin FtsZ, which forms a Z ring at the midcell. FtsZ recruits the other cell division proteins, collectively called the divisome, and the Z ring constricts as the cell divides. We applied live-cell single-molecule imaging to describe the dynamics of the divisome in detail, and to evaluate the individual roles of FtsZ-binding proteins (ZBPs), specifically FtsA and the ZBPs EzrA, SepF and ZapA, in cytokinesis. We show that the divisome comprises two subcomplexes that move differently: stationary ZBPs that transiently bind to treadmilling FtsZ filaments, and a moving complex that includes cell wall synthases. Our imaging analyses reveal that ZBPs bundle FtsZ filaments together and condense them into Z rings, and that this condensation is necessary for cytokinesis.
@article{Squyres8015,
author={Georgia R Squyres, Matthew J Holmes, Sarah R Barger, Betheney R Pennycook, Joel Ryan, Victoria T Yan, Ethan C Garner},
title={Single-molecule imaging reveals that Z-ring condensation is essential for cell division in Bacillus subtilis.},
journal ={Nature microbiology},
volume={},
pages={1--1},
year=2021
}

Andreas Lackner✳︎, Robert Sehlke✳︎, Marius Garmhausen✳︎, Giuliano Giuseppe Stirparo✳︎, Michelle Huth, Fabian Titz-Teixeira, Petra van der Lelij, Julia Ramesmayer, Henry F Thomas, Meryem Ralser, Laura Santini, Elena Galimberti, Mihail Sarov, A F Stewart, Austin Smith, Andreas Beyer, Martin Leeb
Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency.
EMBO J, Art. No. e105776 (2021)
PubMed Source   

In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.
@article{Lackner7975,
author={Andreas Lackner, Robert Sehlke, Marius Garmhausen, Giuliano Giuseppe Stirparo, Michelle Huth, Fabian Titz-Teixeira, Petra van der Lelij, Julia Ramesmayer, Henry F Thomas, Meryem Ralser, Laura Santini, Elena Galimberti, Mihail Sarov, A F Stewart, Austin Smith, Andreas Beyer, Martin Leeb},
title={Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency.},
journal ={The EMBO journal},
volume={},
pages={null--null},
year=2021
}

Rafał Bazan✳︎, Adam Schröfel✳︎, Ewa Joachimiak, Martyna Poprzeczko, Gaia Pigino#, Dorota Wloga#
Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link.
PLoS Genet, 17(3) Art. No. e1009388 (2021)
PubMed Source   

Ciliary beating requires the coordinated activity of numerous axonemal complexes. The protein composition and role of radial spokes (RS), nexin links (N-DRC) and dyneins (ODAs and IDAs) is well established. However, how information is transmitted from the central apparatus to the RS and across other ciliary structures remains unclear. Here, we identify a complex comprising the evolutionarily conserved proteins Ccdc96 and Ccdc113, positioned parallel to N-DRC and forming a connection between RS3, dynein g, and N-DRC. Although Ccdc96 and Ccdc113 can be transported to cilia independently, their stable docking and function requires the presence of both proteins. Deletion of either CCDC113 or CCDC96 alters cilia beating frequency, amplitude and waveform. We propose that the Ccdc113/Ccdc96 complex transmits signals from RS3 and N-DRC to dynein g and thus regulates its activity and the ciliary beat pattern.
@article{Bazan7952,
author={Rafał Bazan, Adam Schröfel, Ewa Joachimiak, Martyna Poprzeczko, Gaia Pigino, Dorota Wloga},
title={Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link.},
journal ={PLoS genetics},
volume={17},
issue ={3},
pages={null--null},
year=2021
}
✳︎ joined first author, # joined corresponding author