Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Phase response curves reveal how biological clocks respond to stimuli applied during different circadian phases but can be costly to produce. Here Masuda et al. show that phase response curves for plants can be reconstructed by monitoring how a desynchronized population responds to a single stimulus.

    • Kosaku Masuda
    • , Isao T. Tokuda
    •  & Hirokazu Fukuda

  • Article
    | Open Access

    Synthetic gene circuits may not function as expected due to the resource competition between modules. Here the authors build cascading bistable switches to achieve two successive cell fate transitions but found a ‘winner-takes-all’ behaviour, which is overcome by a division of labour strategy.

    • Rong Zhang
    • , Hanah Goetz
    •  & Xiao-Jun Tian

  • Article
    | Open Access

    Autocatalytic networks may have started evolution during the origin of life. Here, the authors establish a landscape of thousands of RNA networks by barcoded sequencing and microfluidics, and derive relationships between topology and Darwinian properties such as variation and differential reproduction.

    • Sandeep Ameta
    • , Simon Arsène
    •  & Philippe Nghe

  • Article
    | Open Access

    Secondary ion beam mass spectrometry (SIMS) is a method to obtain a chemical snapshot of biological tissue, but the spatial resolution is low. Here, the authors develop a computational and technology pipeline to localise a chemical signal in SIMS in 3D and sub-25 nm accuracy, called Ion Beam Tomography

    • Ahmet F. Coskun
    • , Guojun Han
    •  & Garry P. Nolan

  • Article
    | Open Access

    In naturally occurring microbial systems, there is a positive relationship between species diversity and productivity of the community. Here the authors perform model selection to find potential amensal interactions that yield robust stable synthetic microbial consortia.

    • Behzad D. Karkaria
    • , Alex J. H. Fedorec
    •  & Chris P. Barnes

  • Article
    | Open Access

    Genome-wide studies of de novo genes have tended to focus on genomic open reading frames (ORFs). Here, Blevins et al. use deep transcriptomics and synteny information to identify de novo transcripts in the yeast Saccharomyces cerevisiae, many of which are expressed from the alternative DNA strand.

    • William R. Blevins
    • , Jorge Ruiz-Orera
    •  & M. Mar Albà

  • Article
    | Open Access

    A diverse array of antigens can trigger allergic reactions. Here the authors present the ‘AllerScan’ programmable phage display library, which is an efficient and unbiased approach for profiling anti-allergen antibody reactivities at cohort scale, with which a key wheat epitope is found to distinguish between wheat allergy and tolerance.

    • Daniel R. Monaco
    • , Brandon M. Sie
    •  & H. Benjamin Larman

  • Article
    | Open Access

    Targeting chromatin regulators to a gene is emerging as powerful tool to control transcription. Here the authors demonstrate the use of nanobodies against chromatin regulators to control gene expression and epigenetic memory.

    • Mike V. Van
    • , Taihei Fujimori
    •  & Lacramioara Bintu

  • Article
    | Open Access

    Some cholesterol-lowering drugs can increase the risk of type 2 diabetes, but the mechanism behind this is not fully understood. Here the authors show that there is a single genetic regulatory module that influences both cholesterol levels and glucose levels, providing a link between cholesterol levels and diabetes.

    • Ariella T. Cohain
    • , William T. Barrington
    •  & Eric E. Schadt

  • Perspective
    | Open Access

    Synthetic biology engineering principles enable two-way communication between living and inanimate substrates. Here the authors consider the development of this bio-informational exchange and propose cyber-physical architectures and applications.

    • Thomas A. Dixon
    • , Thomas C. Williams
    •  & Isak S. Pretorius

  • Article
    | Open Access

    Genetic circuits can be engineered to generate predefined outcomes, however host context is a crucial factor in performance. Here the authors characterise twenty NOT gates in seven different bacteria to understand and predict interoperability and portability across hosts.

    • Huseyin Tas
    • , Lewis Grozinger
    •  & Ángel Goñi-Moreno

  • Article
    | Open Access

    Stochastic fluctuations at the transcriptional level contribute to heterogeneity in isogenic cell populations. Here, the authors engineer TuNR which modulates the variability in gene expression of endogenous human genes independent of their mean expression.

    • Alain R. Bonny
    • , João Pedro Fonseca
    •  & Hana El-Samad

  • Article
    | Open Access

    Macrophages can be polarized by in vitro culture stimuli into M1 or M2 cells, but microenvironments in vivo are more complex. Here the authors analyze cultured macrophages stimulated with a combination of M1 and M2 stimuli by single-cell RNA sequencing, machine learning, and single-cell secretion profiling to show a surprising level of heterogeneity of response.

    • Andrés R. Muñoz-Rojas
    • , Ilana Kelsey
    •  & Kathryn Miller-Jensen

  • Article
    | Open Access

    Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, the authors report an efficient network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of human cerebral organoids.

    • Jong-Chan Park
    • , So-Yeong Jang
    •  & Inhee Mook-Jung

  • Article
    | Open Access

    While temperature impacts the function of all cellular components, it’s hard to rule out how the temperature dependence of cell phenotypes emerged from the dependence of individual components. Here, the authors develop a Bayesian genome scale modelling approach to identify thermal determinants of yeast metabolism.

    • Gang Li
    • , Yating Hu
    •  & Jens Nielsen

  • Article
    | Open Access

    Integration of single cell data modalities increases the richness of information about the heterogeneity of cell states, but integration of imaging and transcriptomics is an open challenge. Here the authors use autoencoders to learn a probabilistic coupling and map these modalities to a shared latent space.

    • Karren Dai Yang
    • , Anastasiya Belyaeva
    •  & Caroline Uhler

  • Article
    | Open Access

    Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.

    • Hannah Peckham
    • , Nina M. de Gruijter
    •  & Claire T. Deakin

  • Article
    | Open Access

    Innate-like T cells such as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells both develop in the thymus. Here the authors use single-cell RNA sequencing to show that mouse iNKT and MAIT share components of developmental regulation, with a transcription factor, Hivep3, implicated for the maturation of both cell types.

    • S. Harsha Krovi
    • , Jingjing Zhang
    •  & Laurent Gapin

  • Article
    | Open Access

    Multiple co-occurring stressors may affect food webs in ways that are not predictable by studying individual stressors. Here the authors apply a network interaction model to a marine food web in the Arctic, finding that nonlinear interactions between stressors can more than double the risk of population collapse compared to simpler simulations.

    • K. R. Arrigo
    • , Gert L. van Dijken
    •  & R. M. Bailey

  • Perspective
    | Open Access

    The IMEx consortium provides one of the largest resources of curated, experimentally verified molecular interaction data. Here, the authors review how IMEx evolved into a fundamental resource for life scientists and describe how IMEx data can support biomedical research.

    • Pablo Porras
    • , Elisabet Barrera
    •  & Sandra Orchard

  • Article
    | Open Access

    Combinatorial treatments have become a standard of care for various complex diseases including cancers. Here, the authors show that combinatorial responses of two anticancer drugs can be accurately predicted using factorization machines trained on large-scale pharmacogenomic data for guiding precision oncology studies.

    • Heli Julkunen
    • , Anna Cichonska
    •  & Juho Rousu

  • Article
    | Open Access

    Bacterial vaginosis (BV) is typically caused by a shift in the vaginal microbiota from a Lactobacillus-dominant community to one colonised by strains of Gardenerella vaginalis and treatment with the antibiotic metronidazole (MNZ) often results in failure and recurrence. Here, the authors use modelling and in vitro assays to show that sequestration of MNZ by Lactobacillus is critical in reducing efficacy and women with a higher pre-treatment Lactobacillus/Gardnerella ratio are more likely to recur.

    • Christina Y. Lee
    • , Ryan K. Cheu
    •  & Kelly B. Arnold

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Understanding evolutionary constraints in antibiotic resistance is crucial for prediction and control. Here, the authors use high-throughput laboratory evolution of Escherichia coli alongside machine learning to identify trade-off relationships associated with drug resistance.

    • Tomoya Maeda
    • , Junichiro Iwasawa
    •  & Chikara Furusawa

  • Article
    | Open Access

    Large volumes of true random numbers are needed for increasing requirements of secure data encryption. Here the authors use the stochastic nature of DNA synthesis to obtain millions of gigabytes of unbiased randomness.

    • Linda C. Meiser
    • , Julian Koch
    •  & Robert N. Grass

  • Article
    | Open Access

    Current efforts to establish synthetic carbon fixation in model heterotrophs rely on expression of heterologous enzymes. Here, the authors explore the presence and activity of a latent CO2-assimilation pathway in E. coli based only on endogenous enzymes and a reversible decarboxylase.

    • Ari Satanowski
    • , Beau Dronsella
    •  & Arren Bar-Even

  • Article
    | Open Access

    The design and optimisation of 3D DNA-origami can be a barrier to rapid application. Here the authors design barrel structure of stacked 2D double helical rings with complex surface patterns.

    • Shelley F. J. Wickham
    • , Alexander Auer
    •  & William M. Shih

  • Article
    | Open Access

    Translatome remodelling controls stress-adaptive protein output. Here the authors reveal that in response to stimuli, eIF5A functions as a pH-regulated translation factor that responds to fermentation-induced acidosis affecting cellular metabolism.

    • Nathan C. Balukoff
    • , J. J. David Ho
    •  & Stephen Lee

  • Article
    | Open Access

    Accurately predicting the behaviour of a genetic circuit remains difficult due to the lack of modularity. Here the authors quantify the effects of resource loading in mammalian systems and develop an endoribonuclease-based feedfoward controller to adapt gene expression to the effects of resource loading.

    • Ross D. Jones
    • , Yili Qian
    •  & Domitilla Del Vecchio

  • Article
    | Open Access

    Building regulatory networks often requires trade-offs between accuracy and speed. Here the authors show in a bistable network the transition from a slow decision making system to a rapid one dominated by small number fluctuations.

    • Ferdinand Greiss
    • , Shirley S. Daube
    •  & Roy Bar-Ziv

  • Article
    | Open Access

    Neuron-astrocyte communication plays a key role in pathophysiology, however systematic approaches to unveil it are limited. Here, the authors propose SEARCHIN, a multi-modal integrated workflow, as a tool to identify cross-compartment ligand-receptor interactions, applied to ALS models.

    • Vartika Mishra
    • , Diane B. Re
    •  & Serge Przedborski

  • Article
    | Open Access

    Conjugative plasmids mediate the spread and maintenance of diverse traits in microbial communities, but the conditions underlying plasmid persistence are poorly understood. Here, Wang and You present a modeling framework for analysis of gene flow and prediction of plasmid persistence and abundance in complex communities.

    • Teng Wang
    •  & Lingchong You

  • Article
    | Open Access

    Morphogen gradients can be dynamic and transient yet give rise to stable cellular patterns. Here the authors show that a synthetic morphogen-induced mutual inhibition circuit produces stable boundaries when the spatial average of morphogens falls within the region of bistability.

    • Paul K. Grant
    • , Gregory Szep
    •  & Andrew Phillips

  • Article
    | Open Access

    The trade-off between growth and production affects the application of engineered microbes. Here, the authors take the minimal cut set approach to predict metabolic reactions for elimination to couple metabolite production strongly with growth and achieve high production of indigoidine in Pseudomonas putida.

    • Deepanwita Banerjee
    • , Thomas Eng
    •  & Aindrila Mukhopadhyay

  • Article
    | Open Access

    Herold et al. present an integrated meta-omics framework to investigate how mixed microbial communities, such as oleaginous bacterial populations in biological wastewater treatment plants, respond with distinct adaptation strategies to disturbances. They show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity.

    • Malte Herold
    • , Susana Martínez Arbas
    •  & Paul Wilmes

  • Article
    | Open Access

    The protein translation machinery is the most expensive cellular subsystem in fast growing bacteria. Providing a detailed mechanistic model for this complex system, the authors show that the translation machinery components are expressed such that their combined cost to the cell is minimal.

    • Xiao-Pan Hu
    • , Hugo Dourado
    •  & Martin J. Lercher

  • Article
    | Open Access

    Distributed multi-omic digitization of clinical specimen across multiple sites is a prerequisite for turning molecular precision medicine into reality. Here, the authors show that coordinated proteotype data acquisition is feasible using standardized MS data acquisition and analysis strategies.

    • Yue Xuan
    • , Nicholas W. Bateman
    •  & Thomas P. Conrads

  • Article
    | Open Access

    Global interaction of chromatin-associated RNAs and DNA can be identified in situ. Here the authors report the genome-wide increase of interchromosomal RNA-DNA interactions and demonstrate the importance of such RNA-DNA contacts exemplified by LINC00607 RNA and SERPINE1 gene’s super enhancer in dysfunctional endothelial cell models.

    • Riccardo Calandrelli
    • , Lixia Xu
    •  & Sheng Zhong

  • Article
    | Open Access

    Tocotrienols are valuable supplementations to α-tocopherol-dominated Vitamin E products. Here, the authors engineer baker’s yeast by combining the heterologous genes from photosynthetic organisms with the endogenous pathway for the production of tocotrienols under cold-shock-triggered temperature control.

    • Bin Shen
    • , Pingping Zhou
    •  & Hongwei Yu

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