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| Open AccessTemporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
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| Open AccessTime-integrated BMP signaling determines fate in a stem cell model for early human development
The interpretation of the key developmental signal BMP remains poorly understood. Here, the authors show that the total time-integrated signaling controls differentiation in a stem cell embryo model and provide a possible mechanism.
- Seth Teague
- , Gillian Primavera
- & Idse Heemskerk
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| Open AccessTime-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle
Stress granules (SGs) are dynamic compartments with a poorly characterized transition in composition and function during prolonged stress. In this study, the authors investigated the dynamic changes in SG constituents during acute to prolonged heat shock using time-resolved proteomic profiling.
- Shuyao Hu
- , Yufeng Zhang
- & Yun Bai
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| Open AccessA semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening
Cell-based phenotypic assays link in vitro discovery to disease pathology. Here, the authors report a semiconductor-based microplate platform to perform high-throughput, high-dimensional “electrical imaging” for label-free assessment of live cell morphology and function.
- Shalaka Chitale
- , Wenxuan Wu
- & Jeffrey Abbott
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Article
| Open AccessConstructing temporal networks with bursty activity patterns
Many real-world systems are characterized by bursty dynamics with interchanging periods of intense activity and quiescence. The authors propose a method to construct temporal networks that match a given activity pattern, and apply it to empirical bursty patterns.
- Anzhi Sheng
- , Qi Su
- & Joshua B. Plotkin
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| Open AccessReconstructing disease dynamics for mechanistic insights and clinical benefit
Understanding disease progression dynamics is critical for diagnostics and treatment, but capturing dynamics is difficult. Here, the authors present a method for modelling disease progression from high dimensional molecular data that enables patient stratification and high-risk disease state identification, showcased in bladder cancer.
- Amit Frishberg
- , Neta Milman
- & Shai S. Shen-Orr
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| Open AccessA general model-based causal inference method overcomes the curse of synchrony and indirect effect
Traditional causal inference methods struggle to distinguish direct causation from synchrony and indirect effects. Here, authors present GOBI that overcomes this by testing a general model’s ability to reproduce data, providing accurate and broadly applicable causality inference for complex systems.
- Se Ho Park
- , Seokmin Ha
- & Jae Kyoung Kim
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| Open AccessLearning perturbation-inducible cell states from observability analysis of transcriptome dynamics
A major challenge in biotechnology and biomanufacturing is the identification of a set of biomarkers for perturbations and metabolites of interest. Here, the authors develop a data-driven, transcriptome-wide approach to rank perturbation-inducible genes from time-series RNA sequencing data for the discovery of analyte-responsive promoters.
- Aqib Hasnain
- , Shara Balakrishnan
- & Enoch Yeung
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Article
| Open AccessDamage dynamics and the role of chance in the timing of E. coli cell death
To understand why genetically identical cells die at different times the authors measured damage dynamics in individual cells. They report lifespan variation comes not from initial conditions but from stochastic accumulation of damage that saturates repair systems.
- Yifan Yang
- , Omer Karin
- & Uri Alon
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Article
| Open AccessA comprehensive platform for analyzing longitudinal multi-omics data
The analysis of longitudinal bulk and single-cell multi-omics data is a highly complex task. Here, the authors introduce PALMO, a software platform with five modules to analyse longitudinal bulk and single-cell multi-omics data, which is extensively tested in external datasets that include multiple omics modalities.
- Suhas V. Vasaikar
- , Adam K. Savage
- & Xiao-jun Li
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| Open AccessParallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Epithelial-to-mesenchymal transition (EMT) is a complex process regulated at multiple molecular levels. Here, the authors implement an analytic framework - PAMAF - to integrate data from twelve distinct omics modalities, which they use to understand the molecular changes and regulation during EMT in vitro.
- Indranil Paul
- , Dante Bolzan
- & Andrew Emili
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| Open AccessTime-resolved in vivo ubiquitinome profiling by DIA-MS reveals USP7 targets on a proteome-wide scale
Combining improved sample preparation, data-independent acquisition mass spectrometry and deep learning, the authors develop a workflow for more robust and precise quantitative ubiquitinome profiling. They use this method to characterize targets of the deubiquitinase USP7 and effects of USP7 inhibitors.
- Martin Steger
- , Vadim Demichev
- & Henrik Daub
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| Open AccessEukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis
Yeast exhibit oscillations that share features with circadian rhythms. The authors show that bioenergetic constraints promote oscillatory behaviour: resources are stored until supplies can support translational bursting, this is licensed by ion transport and release from membrane-less compartments.
- John S. O’Neill
- , Nathaniel P. Hoyle
- & Helen C. Causton
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| Open AccessAlveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis
Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis.
- Maximilian Strunz
- , Lukas M. Simon
- & Herbert B. Schiller
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| Open AccessThe pause-initiation limit restricts transcription activation in human cells
Gene activation requires an increase of successful initiation events. Here, by employing a genome-wide kinetic analysis of transcription, the authors showed that gene activation generally requires a decrease in RNA Polymerase II (Pol II) promoter-proximal pausing while transcription of enhancer elements is not limited by Pol II pausing.
- Saskia Gressel
- , Björn Schwalb
- & Patrick Cramer
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| Open AccessDynamic molecular changes during the first week of human life follow a robust developmental trajectory
The first week of life impacts health for all of life, but the mechanisms are little-understood. Here the authors extract multi-omic data from small volumes of blood to study the dynamic molecular changes during the first week of life, revealing a robust developmental trajectory common to different populations.
- Amy H. Lee
- , Casey P. Shannon
- & Tobias R. Kollmann
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| Open AccessKingdom-wide comparison reveals the evolution of diurnal gene expression in Archaeplastida
The diurnal cycle exerts influences on various aspects of plant biology. Here, the authors generate and compare diurnal transcriptomics data from nine members of Archaeplastida representing major clades.
- Camilla Ferrari
- , Sebastian Proost
- & Marek Mutwil
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| Open AccessSingle cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth
The respiratory system is transformed in terms of functional change at birth to adapt to breathing air. Here, the authors examine the molecular changes behind the first breath in the mouse by Drop-seq based RNA sequencing, identifying activation of the unfolded protein response as a perinatal adaptation of the lung.
- Minzhe Guo
- , Yina Du
- & Yan Xu
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| Open AccessCausal decomposition in the mutual causation system
Causality inference in time series analysis based on temporal precedence principle between cause and effect fails to detect mutual causal interactions. Here, Yang et al. introduce a causal decomposition approach based on the covariation principle of cause and effect that overcomes this limitation.
- Albert C. Yang
- , Chung-Kang Peng
- & Norden E. Huang
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| Open AccessSerotonin-dependent kinetics of feeding bursts underlie a graded response to food availability in C. elegans
Regulating food intake is an important physiological mechanism. Here, the authors use a custom microfluidic device to investigate feeding dynamics inC. elegans, and identify roles of serotonergic neurons in regulating bursts of feeding in response to food availability.
- Kyung Suk Lee
- , Shachar Iwanir
- & Erel Levine
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| Open AccessInferring time derivatives including cell growth rates using Gaussian processes
High-throughput time-series data is increasingly available, yet estimating time-derivatives from such data can remain a challenge. Here, the authors provide a non-parametric method for inferring the first and second time-derivatives from multiple replicates of time-series data and for estimating errors in this inference and in any summary statistics.
- Peter S. Swain
- , Keiran Stevenson
- & Teuta Pilizota