Systems biology articles within Nature Communications

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  • Article
    | Open Access

    It’s challenging to capture “hidden” drivers that may not be genetically-altered or differentially-expressed from omics data. Here the authors developed NetBID2, a comprehensive network-based toolbox with versatile features, enabling the integration of multi-omics data to expose such hidden drivers.

    • Xinran Dong
    • , Liang Ding
    •  & Jiyang Yu

  • Article
    | Open Access

    Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. Here the authors combine construction of over 20 synthetic gene regulatory networks with mathematical modeling to exemplify how gene regulatory networks provide robustness in face of mutations while enabling transitions to innovative phenotypes.

    • Javier Santos-Moreno
    • , Eve Tasiudi
    •  & Yolanda Schaerli

  • Article
    | Open Access

    Cell-free genetically encoded biosensors have been developed to detect small molecules and nucleic acids, but they have yet to be reliably engineered to detect proteins. Here the authors develop an automated platform to convert protein-binding RNA aptamers into riboswitch sensors that operate within low-cost cell-free assays.

    • Grace E. Vezeau
    • , Lipika R. Gadila
    •  & Howard M. Salis

  • Article
    | Open Access

    Enabling high-bandwidth communication between cells is a prerequisite for engineering multicellular consortia that can perform sophisticated computations and functions. Here, the authors design a framework for addressable and adaptable DNA-based communication and implement it using plasmid conjugation in a E. coli population.

    • John P. Marken
    •  & Richard M. Murray

  • Article
    | Open Access

    Plasmid acquisition imposes a transient burden on bacterial hosts. Here, authors show this burden results in a tradeoff between growth and lag that dictates plasmid fate, favoring intermediate cost plasmids over both low and high cost counterparts.

    • Mehrose Ahmad
    • , Hannah Prensky
    •  & Allison J. Lopatkin

  • Article
    | Open Access

    At the molecular level, the evolution of life is driven by the generation and diversification of adaptation mechanisms. Here Araujo and Liotta identify definitive and universal structural requirements for adaptation via intermolecular interactions.

    • Robyn P. Araujo
    •  & Lance A. Liotta

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The interconnected network of cellular metabolism is potentially prone to generating oscillatory behaviour. Here, the authors use single-cell FRET measurements of pyruvate levels to reveal large periodic fluctuations in bacterial glycolysis.

    • Shuangyu Bi
    • , Manika Kargeti
    •  & Victor Sourjik

  • Article
    | Open Access

    Synthetic circuits that can record in vivo signaling networks is critical in elucidating developmental process. Here, the authors describe the engineering and application of synthetic in vivo recorders with different promoters that can drive spatiotemporally-specific integrase switching during lateral root initiation.

    • Sarah Guiziou
    • , Cassandra J. Maranas
    •  & Jennifer L. Nemhauser

  • Article
    | Open Access

    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

  • Perspective
    | Open Access

    In this perspective, the authors hypothesise that glial senescence, requiring senescent microglia burden, perpetuates further aging, Alzheimer’s pathologies, and senescence. Increasing glial senescence is proposed as necessary to drive individuals from healthy cognition into cognitive decline and dementia.

    • Victor Lau
    • , Leanne Ramer
    •  & Marie-Ève Tremblay

  • Article
    | Open Access

    Large-scale disease-association data are widely used for pathomechanism mining, even if disease definitions used for annotation are mostly phenotype-based. Here, the authors show that this bias can lead to a blurred view on disease mechanisms, highlighting the need for close-up studies based on molecular data for well-characterized patient cohorts.

    • Sepideh Sadegh
    • , James Skelton
    •  & David B. Blumenthal

  • Article
    | Open Access

    Comprehensive understanding of the human protein-protein interaction network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Here the authors summarize the community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict protein-protein interactions.

    • Xu-Wen Wang
    • , Lorenzo Madeddu
    •  & Yang-Yu Liu

  • Article
    | Open Access

    Context-dependency of mammalian transcriptional elements has hindered the quantitative investigation of multigene expression stoichiometry and its biological functions. Here the authors present a host-orthogonal transcriptional system that drives tunable gene expression in mammalian cells, enabling predictive fine-tuning of multi-gene expression stoichiometry and the production optimization of virus-like particles from mammalian cells.

    • Chenrui Qin
    • , Yanhui Xiang
    •  & Chunbo Lou

  • Article
    | Open Access

    Living things rely on extremely sensitive molecular circuits. Here, authors uncover a universal structural limit on kinetic scheme sensitivity, with implications for gene regulation & the functions of condensates.

    • Jeremy A. Owen
    •  & Jordan M. Horowitz

  • Article
    | Open Access

    Antibiotics are a key control mechanism for synthetic biology and microbiology. Here, using an optogenetic recombinase, the authors develop genetic constructs where antibiotic resistance levels in bacteria can be controlled using light.

    • Michael B. Sheets
    • , Nathan Tague
    •  & Mary J. Dunlop

  • Article
    | Open Access

    The circulatory lipidome is a valuable source for disease markers, but reliable marker discovery requires continuous development of lipidomic methods for large-scale clinical profiling. Here, the authors present a 4-dimensional lipidomics solution for confident and reproducible blood lipidome profiling.

    • Raissa Lerner
    • , Dhanwin Baker
    •  & Laura Bindila

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The extensive information capacity of DNA makes it an attractive alternative to traditional data storage. DNA-Aeon is a DNA data storage solution that can correct all error types commonly observed in DNA storage, while encoding data into sequences that meet user-defined constraints such as GC content, homopolymer length, and no undesired motifs.

    • Marius Welzel
    • , Peter Michael Schwarz
    •  & Dominik Heider

  • Article
    | Open Access

    RNA provides a unique readout of a cell’s identity, physiologic status, and phenotype. Here the authors deliver an RNA sensing system that can use the information contained within cellular RNA to selectively control the activity of genetic programs.

    • Lauren Gambill
    • , August Staubus
    •  & James Chappell

  • Article
    | Open Access

    Understanding the heterogeneity of growth, response to therapy and progression dynamics in metastatic colorectal cancer (mCRC) remains critical. Here, the authors analyse lesion-specific response heterogeneity in 4,308 mCRC patients and find that organ-level progression sequence is associated with long-term survival.

    • Jiawei Zhou
    • , Amber Cipriani
    •  & Yanguang Cao

  • Article
    | Open Access

    Shortest paths between the nodes of complex networks are challenging to obtain if the information on network structure is incomplete. Here the authors show that the shortest paths are geometrically localized in hyperbolic representations of networks, and can be detected even if the large amount of network links are missing. The authors demonstrate the utility of geometric pathfinding in Internet routing and the reconstruction of cellular pathways.

    • Maksim Kitsak
    • , Alexander Ganin
    •  & Igor Linkov

  • Article
    | Open Access

    Longitudinal proteomics holds great promise for biomarker discovery, but the data interpretation has remained a challenge. Here, the authors evaluate several tools to detect longitudinal differential expression in proteomics data and introduce RolDE, a robust reproducibility optimization approach.

    • Tommi Välikangas
    • , Tomi Suomi
    •  & Laura L. Elo

  • Article
    | Open Access

    Synthetic biology often involves engineering microbial strains to express high-value proteins. Here the authors build deep learning predictors of protein expression from sequence that deliver accurate models with fewer data than previously assumed, helping to lower costs of model-driven strain design.

    • Evangelos-Marios Nikolados
    • , Arin Wongprommoon
    •  & Diego A. Oyarzún

  • Article
    | Open Access

    The biosynthetic pathway of type II ganoderic acids (GAs) in Ganoderma lucidum, a traditional medicinal mushroom, is unknown. Here, the authors assemble the genome of type II GAs accumulating accession, identify CYPs involving in type II GAs biosynthesis, and achieve their production in engineered baker’s yeast.

    • Wei Yuan
    • , Chenjian Jiang
    •  & Han Xiao

  • Article
    | Open Access

    It is unclear what constraints exist on cellular life in frigid environments. Here, the authors demonstrate that reactive oxygen species and gene-expression speed impose a barrier to replication at low temperatures in yeast, with lower levels enabling quicker replication, and develop a model to describe this phenomenon.

    • Diederik S. Laman Trip
    • , Théo Maire
    •  & Hyun Youk

  • Article
    | Open Access

    Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.

    • Jingbo Qie
    • , Yang Liu
    •  & Chen Ding

  • Article
    | Open Access

    Here, the authors present a method to build genetically personalised metabolic models across tissues to estimate individualised reaction fluxes. A fluxome-wide association study in UK Biobank identifies fluxes associated with metabolites and coronary artery disease.

    • Carles Foguet
    • , Yu Xu
    •  & Michael Inouye

  • Article
    | Open Access

    Artificial receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications and/or improper folding. Here, the authors engineer diverse synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum, or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites.

    • Mohamed Mahameed
    • , Pengli Wang
    •  & Martin Fussenegger

  • Article
    | Open Access

    Protein phosphorylation is a ubiquitous post-translational modification used to regulate cellular processes and proteome architecture by modulating protein-protein interactions. Here the authors optimize genetically encoded phosphothreonine to study the regulation of CHK2 kinase using large-scale DNA arrays that enable phosphoproteome expression techniques to identify sitespecific overlap between CHK2 substrates and 14-3-3 interactions.

    • Jack M. Moen
    • , Kyle Mohler
    •  & Jesse Rinehart

  • Article
    | Open Access

    The UCLA Ribonomics group reports that the nuclear export efficiency of innate immune mRNAs varies over a hundred-fold range such that for many genes only a small fraction of the newly synthesized premRNA reaches the cytoplasm. They show that nuclear export and cytoplasmic decay rates are correlated thereby ensuring similar expression levels of short-lived and long-lived mRNAs.

    • Diane Lefaudeux
    • , Supriya Sen
    •  & Sri Kosuri

  • Article
    | Open Access

    Environmental exposures in early life can have lasting health effects, but the molecular mechanisms are not well understood. Here, the authors discover >1000 associations between exposure factors and child multi-omics profiles, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions.

    • Léa Maitre
    • , Mariona Bustamante
    •  & Martine Vrijheid

  • Article
    | Open Access

    By comprehensively mapping the impact that different classes of mutations (substitutions, insertions, deletions) have on the ability of the amyloid beta peptide to nucleate amyloids, the authors identify a large set of likely pathogenic variants of amyloid beta that are specifically enriched at its polar N-terminal region.

    • Mireia Seuma
    • , Ben Lehner
    •  & Benedetta Bolognesi

  • Article
    | Open Access

    Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here the authors present a tunable, modular, and portable feedforward controller that allows dynamic modulation of a genes expression to possibly high-levels without substantially affecting growth rate.

    • Carlos Barajas
    • , Hsin-Ho Huang
    •  & Domitilla Del Vecchio

  • Article
    | Open Access

    Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

    • Jie Sun
    • , Ming Wang
    •  & Baohua Liu

  • Article
    | Open Access

    Ant and honeybee workers specialize on certain tasks and also on zones within the nest; but how do they avoid straying into the wrong zone? The authors conduct automated tracking experiments following thousands of individuals, revealing that workers use context-dependent rules to navigate inside the nest.

    • Thomas O. Richardson
    • , Nathalie Stroeymeyt
    •  & Laurent Keller

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