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| Open AccessA neural-mechanistic hybrid approach improving the predictive power of genome-scale metabolic models
Mechanistic models estimate the phenotype of microorganisms in different environments but may have limited predictive capabilities. Here, authors develop trainable hybrid models with improved predictability using mechanistic insights and smaller training sets than conventional machine learning techniques.
- Léon Faure
- , Bastien Mollet
- & Jean-Loup Faulon
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| Open AccessPositive feedback induces switch between distributive and processive phosphorylation of Hog1
How cells shape signalling dynamics in MAPK cascades remains unclear. Here the authors combine mathematical modelling with in vivo validation to uncover a novel feedback mechanism that increases processivity and robustness of the yeast Hog1 module.
- Maximilian Mosbacher
- , Sung Sik Lee
- & Manfred Claassen
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Article
| Open AccessUsing high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events
Here, the authors simulate COVID-19 outbreaks on an empirical contact network derived from digital contact data collected on cruise ships. They model impacts of different control measures and find that combinations of measures, particularly vaccination and rapid antigen testing, are important for mitigating outbreaks.
- Rachael Pung
- , Josh A. Firth
- & Adam J. Kucharski
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| Open AccessThe basis of easy controllability in Boolean networks
Boolean networks allow a simplified representation of interactions. Here, the authors systematically analyze regulation in dozens of biological Boolean networks, finding mathematical regularities that suggest biological systems could be controlled through a relatively small number of components.
- Enrico Borriello
- & Bryan C. Daniels
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Article
| Open AccessA generative network model of neurodevelopmental diversity in structural brain organization
The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.
- Danyal Akarca
- , Petra E. Vértes
- & Duncan E. Astle
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Article
| Open AccessRobustness and lethality in multilayer biological molecular networks
Robustness is a prominent feature of most biological systems, but most of the current efforts have been focused on studying homogeneous molecular networks. Here the authors propose a comprehensive framework for understanding how the interactions between genes, proteins, and metabolites contribute to the determinants of robustness.
- Xueming Liu
- , Enrico Maiorino
- & Amitabh Sharma
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| Open AccessReconciling qualitative, abstract, and scalable modeling of biological networks
Boolean Networks are a well-established model of biological networks, but usual interpretations can preclude the prediction of behaviours observed in quantitative systems. The authors introduce Most Permissive Boolean Networks, which are shown not to miss any behaviour achievable by the corresponding quantitative model.
- Loïc Paulevé
- , Juri Kolčák
- & Stefan Haar
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| Open AccessMultistable and dynamic CRISPRi-based synthetic circuits
Synthetic circuits based on CRISPRi have not achieved multistable and dynamic behaviors. Here the authors build an oscillator, a toggle switch and an incoherent feed-forward loop using CRISPRi, and provide a mathematical model suggesting that unspecific binding in CRISPRi enables multistability.
- Javier Santos-Moreno
- , Eve Tasiudi
- & Yolanda Schaerli
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| Open AccessTransient genome-wide interactions of the master transcription factor NLP7 initiate a rapid nitrogen-response cascade
Conventional methods cannot reveal transient transcription factors (TFs) and targets interactions. Here, Alvarez et al. capture both stable and transient TF-target interactions by time-series ChIP-seq and/or DamID-seq in a cell-based TF perturbation system and show NLP7 as a master TF to initiate a rapid nitrogen-response cascade.
- José M. Alvarez
- , Anna-Lena Schinke
- & Gloria M. Coruzzi
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Article
| Open AccessCompetitive endogenous RNA is an intrinsic component of EMT regulatory circuits and modulates EMT
Competitive endogenous RNAs help to regulate biological processes by regulating miRNA activity levels. Here the author show TGFBI acts as a ceRNA for miR-21 in the epithelial-to-mesenchymal transition.
- Yuwei Liu
- , Mengzhu Xue
- & Peng Wang
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| Open AccessDynamic intercellular transport modulates the spatial patterning of differentiation during early neural commitment
How heterogeneities arise in stem cell populations remains unclear. Here, Glen et al. find that in ESC colonies cell cycle asynchronies modulate gap junctions, causing variation in intracellular signalling molecule diffusion between cells, and ultimately in spatial heterogeneity in differentiation.
- Chad M. Glen
- , Todd C. McDevitt
- & Melissa L. Kemp
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| Open AccessDynamic network biomarker indicates pulmonary metastasis at the tipping point of hepatocellular carcinoma
Biomarkers of the tipping point before metastasis in hepatocellular carcinoma (HCC) could help stratify patient treatment. Here, the authors study dynamic network biomarkers to identify CALM3 as a potential suppressor of metastasis, the level of which can predict overall survival and relapse-free survival in postoperative HCC.
- Biwei Yang
- , Meiyi Li
- & Jinglin Xia
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| Open AccessNetwork dynamics-based cancer panel stratification for systemic prediction of anticancer drug response
Genomic alterations underlie the variability of drug responses between cancers, but our mechanistic understanding is limited. Here the authors use the p53 network to study how rewiring of signalling networks by genomic alterations impact their dynamic response to pharmacological perturbation.
- Minsoo Choi
- , Jue Shi
- & Kwang-Hyun Cho
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Article
| Open AccessCrosstalk and the evolvability of intracellular communication
The evolutionary rationale behind the extensive crosstalk between Metazoan signalling pathways remains elusive. Here the authors provide evidence that crosstalk in the human signalling network evolves as a means to allow efficient diversification of cellular responses to the same signals between different cell types.
- Michael A. Rowland
- , Joseph M. Greenbaum
- & Eric J. Deeds
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Article
| Open AccessR2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein
The R2TP/Prefoldin-like cochaperone complex is involved in the assembly of a number of protein complexes. Here the authors provide evidence that RUVBL1/RUVBL2, subunits of that cochaperone complex, directly interact with ZNHIT2 to regulate assembly of U5 small ribonucleoprotein.
- Philippe Cloutier
- , Christian Poitras
- & Benoit Coulombe
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Article
| Open AccessSignal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states
In biological systems, timing is often critical to the interpretation of signals that determine cell fate. Here the authors demonstrate how single cells and cellular populations respond dynamically to pulsatile stimulation by TNFα and IL-1β, and suggest a mechanism by which the two cytokines can synergistically modulate inflammation.
- Antony Adamson
- , Christopher Boddington
- & Pawel Paszek
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Article
| Open AccessLong-term neural and physiological phenotyping of a single human
Large-scale, multimodal phenotypic characterisation is a valuable tool to explore brain function. Poldrack et al. collect and relate MRI, psychological, physiological, metabolic and gene expression data from a single human over an 18 month period, providing a rich resource for future studies.
- Russell A. Poldrack
- , Timothy O. Laumann
- & Jeanette A. Mumford
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| Open AccessControllability of structural brain networks
Cognitive control is fundamental to human intelligence, yet the principles constraining the neural dynamics of cognitive control remain elusive. Here, the authors use network control theory to demonstrate that the structure of brain networks dictates their functional role in controlling dynamics.
- Shi Gu
- , Fabio Pasqualetti
- & Danielle S. Bassett
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| Open AccessA proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting
Integrins are activated by many extracellular cues and respond by assembling diverse signalling complexes. Byron et al.use activation state-specific antibodies to proteomically characterize these complexes, and provide insight into integrin-dependent microtubule stabilization.
- Adam Byron
- , Janet A. Askari
- & Martin J. Humphries
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Article
| Open AccessQuality versus quantity of social ties in experimental cooperative networks
The effect of the rate of forming and breaking social ties on cooperative behaviour is not clear. Here the authors experimentally test the effect of rewiring the connections between individuals, and find that optimal levels of cooperation are achieved at intermediate levels of change in ties.
- Hirokazu Shirado
- , Feng Fu
- & Nicholas A. Christakis
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Realistic control of network dynamics
Nonlinearity is a hallmark of complex networks, but has generally been regarded as an obstacle to controlling their behaviour. Here Cornelius et al.show how nonlinear dynamics can be harnessed to control a network and drive it to desired states.
- Sean P. Cornelius
- , William L. Kath
- & Adilson E. Motter