Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Innate immunity combines intra- and intercellular signalling to develop responses that limit pathogen spread. Here the authors analyse feedback and feedforward loops connecting IRF3, NF-κB and STAT pathways, and suggest they allow coordinating cell fate decisions in cellular populations in response to the virus-mimicking agent poly(I:C).

    • Maciej Czerkies
    • , Zbigniew Korwek
    •  & Tomasz Lipniacki

  • Article
    | Open Access

    How pathogens maintain phenotypic robustness during infection is poorly understood. Here the authors couple the virulence regulatory network (VRN) of the pathogen R. solanacearum to a model of its metabolic network, and find that the VRN activates functionally redundant primary metabolism genes to promote phenotypic robustness during infection.

    • Rémi Peyraud
    • , Ludovic Cottret
    •  & Stéphane Genin

  • Article
    | Open Access

    While gene expression noise in single-celled organisms is well understood, it is less so in the context of tissues. Here the authors show that coupling between cells in tissues can increase or decrease cell-to-cell variability depending on the level of noise intrinsic to the regulatory networks.

    • Stephen Smith
    •  & Ramon Grima

  • Article
    | Open Access

    A unified framework to understand gene expression noise is still lacking. Here the authors derive a universal theorem relating the biological noise with dynamics of birth and death processes and present a model of transcription dynamics, allowing analytical prediction of the dependence of mRNA noise on mRNA lifetime variability.

    • Seong Jun Park
    • , Sanggeun Song
    •  & Jaeyoung Sung

  • Article
    | Open Access

    Single-cell RNA sequencing (scRNA-seq) data provides information on transcriptomic heterogeneity within cell populations. Here, Risso et al develop ZINB-WaVE for low-dimensional representations of scRNA-seq data that account for zero inflation, over-dispersion, and the count nature of the data.

    • Davide Risso
    • , Fanny Perraudeau
    •  & Jean-Philippe Vert

  • Article
    | Open Access

    How gene regulatory pathways control cell fate decisions in single cells is not fully understood. Here the authors present an integrated dual-input microfluidic chip and a linked analysis software, enabling tracking of gene regulatory responses of single bacterial cells to changing conditions.

    • Matthias Kaiser
    • , Florian Jug
    •  & Erik van Nimwegen

  • Article
    | Open Access

    The isolation of single cells while retaining context is important for quantifying cellular heterogeneity but technically challenging. Here, the authors develop a high-throughput, scalable workflow for microscopy-based single cell isolation using machine-learning, high-throughput microscopy and laser capture microdissection.

    • Csilla Brasko
    • , Kevin Smith
    •  & Peter Horvath

  • Article
    | Open Access

    Transcriptome data provide only a partial picture of disease states. Here, via integration of transcript-, protein abundance and protein turnover data for a mouse model of cardiac hypertrophy, the authors uncover additional disease gene signatures, and show that turnover data sheds unique light on posttranslational regulation.

    • Edward Lau
    • , Quan Cao
    •  & Peipei Ping

  • Article
    | Open Access

    The ability to combine the production of multiple biologics into a single ‘on demand’ system could help in situations where resources are limited. Here the authors demonstrate a proof-of-concept approach for the co-production of three biologics, allowing singular, mixed and combination drug products.

    • Jicong Cao
    • , Pablo Perez-Pinera
    •  & Timothy K. Lu

  • Article
    | Open Access

    Somatic copy number alterations (SCNA) can confound gene co-expression analysis in cancers. Here the authors develop a method to remove the effects of SCNA in co-expression analysis, improving the analysis of network rewiring in cancer, and provide a database with adjusted data from TCGA.

    • Ling Cai
    • , Qiwei Li
    •  & Guanghua Xiao

  • Article
    | Open Access

    Noisy gene expression can cause stochasticity in the expression of plant traits. Here, Araújo et al. use a dual reporter system of protein expression in Arabidopsis to show that expression noise is lowest in stomata relative to other tissues and that leaf cells are coupled with respect to noise.

    • Ilka Schultheiß Araújo
    • , Jessica Magdalena Pietsch
    •  & Martin Hülskamp

  • Article
    | Open Access

    Rising rates of peanut allergy pose a public health problem. Here, the authors profile blood transcriptomes during double-blind, placebo-controlled oral challenge in peanut-allergic children to identify gene and cell composition changes, and construct causal networks to detect key allergic reaction drivers.

    • C. T. Watson
    • , A. T. Cohain
    •  & S. Bunyavanich

  • Article
    | Open Access

    An E. coli strain able to use CO2 fixation for sugar synthesis was previously generated by experimental evolution of an engineered strain. Here, Herz et al. show that specific mutations in five genes, encoding carbon metabolism enzymes or key regulators, are sufficient to enable robust growth of the strain.

    • Elad Herz
    • , Niv Antonovsky
    •  & Ron Milo

  • Article
    | Open Access

    DNA loops are a ubiquitious feature of gene regulation across the kingdoms of life. Here the authors design a Cas9-based dimerization system for inducing DNA loops in E. coli, allowing activation and rewiring of gene expression.

    • Nan Hao
    • , Keith E. Shearwin
    •  & Ian B. Dodd

  • Article
    | Open Access

    Cybergenetics aims to monitor and regulate cellular processes in real-time using computer monitoring and feedback of biological readouts. Here the authors use a feedback loop and periodic forcing to maintain cells with a bistable synthetic circuit near its unstable state.

    • Jean-Baptiste Lugagne
    • , Sebastián Sosa Carrillo
    •  & Pascal Hersen

  • Article
    | Open Access

    IgG glycosylation is an important factor in immune function, yet the molecular details of protein glycosylation remain poorly understood. The data-driven approach presented here uses large-scale plasma IgG mass spectrometry measurements to infer new biochemical reactions in the glycosylation pathway.

    • Elisa Benedetti
    • , Maja Pučić-Baković
    •  & Jan Krumsiek

  • Article
    | Open Access

    Dysregulation of insulin secretion dynamics plays a role in diabetes development. Here, the authors build a mathematical model of hepatic insulin signaling and propose a sequential model of post-meal control of glucose and lipids, according to which delayed aPKC suppression would contribute to selective hepatic insulin resistance.

    • Gang Zhao
    • , Dagmar Wirth
    •  & Michael Meyer-Hermann

  • Article
    | Open Access

    Cancer is caused by accumulating genetic mutations. Here, the authors investigate the cooperative effect of these mutations in colorectal cancer patients and identify a giant cluster of mutation-propagating modules that undergoes percolation transition during tumorigenesis.

    • Dongkwan Shin
    • , Jonghoon Lee
    •  & Kwang-Hyun Cho

  • Article
    | Open Access

    Fast-growing bacteria produce many proteins in excess of what seems optimal for exponential growth. Here, the authors present a mathematical model and experimental evidence supporting that this overexpression serves as a strategic reserve to quickly meet demand upon sudden improvement in growth conditions.

    • Matteo Mori
    • , Severin Schink
    •  & Terence Hwa

  • Article
    | Open Access

    Trisomy 21 (T21) is a major cause of Down syndrome but little is known about its impact on the cellular proteome. Here, the authors define the proteome of T21 fibroblasts and its turnover and also map proteomic differences in monozygotic T21-discordant twins, revealing extensive, organelle-specific changes caused by T21.

    • Yansheng Liu
    • , Christelle Borel
    •  & Ruedi Aebersold

  • Article
    | Open Access

    Deactivated Cas9 fused to transactivation domains can be used to control gene expression, however its presence can prevent rapid switching between different regulatory states. Here the authors generate conditionally degradable dCas9 and Cpf1 proteins for multidimensional control of functional activity.

    • Dirk A. Kleinjan
    • , Caroline Wardrope
    •  & Susan J. Rosser

  • Article
    | Open Access

    The contribution of metabolic pathways to protein secretion is largely unknown. Here, the authors find conserved metabolic patterns in yeast by examining genome-wide transcriptional responses in high protein secretion mutants and reveal critical factors that can be tuned for efficient protein secretion.

    • Mingtao Huang
    • , Jichen Bao
    •  & Jens Nielsen

  • Article
    | Open Access

    Naturally evolved regulatory circuits have hierarchical layers of signal generation and processing. Here, the authors emulate these networks using feedback-controlled DNA circuits that convert upstream signaling to downstream enzyme activity in a switchable memories circuit.

    • Lenny H. H. Meijer
    • , Alex Joesaar
    •  & Tom F. A. de Greef

  • Article
    | Open Access

    Commitment to different fates by differentiating pluripotent cells depends upon integration of external and internal signals. Here the authors analyse the entry of mouse embryonic stem cells into retinoic acid-mediated differentiation using single cell transcriptomics with high temporal resolution.

    • Stefan Semrau
    • , Johanna E. Goldmann
    •  & Alexander van Oudenaarden

  • Article
    | Open Access

    Existing transcriptional regulatory networks models fall short of deciphering the cooperation between multiple transcription factors on dynamic gene expression. Here the authors develop an integrative method that combines gene expression and transcription factor-DNA binding data to decode transcription regulatory logics.

    • Bin Yan
    • , Daogang Guan
    •  & Hailong Zhu

  • Article
    | Open Access

    Genetic drift can reduce fitness in small populations by counteracting selection against deleterious mutations. Here, LaBar and Adami demonstrate through a mathematical model and simulations that small populations tend to evolve to drift-robust fitness peaks, which have a low likelihood of slightly-deleterious mutations.

    • Thomas LaBar
    •  & Christoph Adami

  • Article
    | Open Access

    Genetic isolation of a genetically modified organism represents a useful strategy for biocontainment. Here the authors use dCas9-VP64-driven gene expression to construct a ‘species-like’ barrier to reproduction between two otherwise compatible populations.

    • Maciej Maselko
    • , Stephen C. Heinsch
    •  & Michael J. Smanski

  • Article
    | Open Access

    Peptide CSP regulates natural competence in pneumococci and has been proposed as a quorum-sensing signal or a probe for sensing environmental cues. Here, the authors show that CSP levels can indeed act as an indicator of cell density and also incorporate information on environmental factors or cell history.

    • Stefany Moreno-Gámez
    • , Robin A. Sorg
    •  & Jan-Willem Veening

  • Article
    | Open Access

    Gene expression is a noisy process, but it is not known how noise in gene expression changes during the aging of single cells. Here the authors show that noise decreases during normal aging, and provide support for aging-associated increases in chromatin state transitions governing noise reduction.

    • Ping Liu
    • , Ruijie Song
    •  & Murat Acar

  • Article
    | Open Access

    Although networks of interacting genes and metabolic reactions are interdependent, they have largely been treated as separate systems. Here the authors apply a statistical framework for interdependent networks to E. coli, and show that it is sensitive to gene and protein perturbations but robust against metabolic changes.

    • David F. Klosik
    • , Anne Grimbs
    •  & Marc-Thorsten Hütt

  • Article
    | Open Access

    Cells are exposed to shifts in environmental pH, which direct their metabolism and behavior. Here the authors design pH-sensing riboswitches to create a gene expression program, digitalize the system to respond to a narrow pH range and apply it to evolve host cells with improved tolerance to a variety of organic acids.

    • Hoang Long Pham
    • , Adison Wong
    •  & Matthew Wook Chang

  • Article
    | Open Access

    Eukaryotic cells rely on the ubiquitin-proteasome system for selective degradation of proteins, a process vital to organismal fitness. Here the authors show that the number of repeats in the polyubiquitin gene is evolutionarily unstable within and between yeast species, and that this variability may tune the cell’s capacity to respond to sudden environmental perturbations.

    • Rita Gemayel
    • , Yudi Yang
    •  & Kevin J. Verstrepen

  • Article
    | Open Access

    High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.

    • Ioannis K. Zervantonakis
    • , Claudia Iavarone
    •  & Joan S. Brugge

  • Article
    | Open Access

    Screening libraries of genetically engineered microbes for secreted products is limited by the available assay throughput. Here the authors combine aptamer-based fluorescent detection with droplet microfluidics to achieve high throughput screening of yeast strains engineered for enhanced tyrosine or streptavidin production.

    • Joseph Abatemarco
    • , Maen F. Sarhan
    •  & Adam R. Abate

  • Article
    | Open Access

    The quiescence-exit process is noisy even in genetically identical cells under the same environmental conditions. Here the authors show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history prior to quiescence entry.

    • Xia Wang
    • , Kotaro Fujimaki
    •  & Guang Yao

  • Article
    | Open Access

    Gene networks evolve by transcription factor (TF) duplication and divergence of their binding site specificities, but little is known about the global constraints at play. Here, the authors study the coevolution of TFs and binding sites using a biophysical-evolutionary approach, and show that the emerging complex fitness landscapes strongly influence regulatory evolution with a role for crosstalk.

    • Tamar Friedlander
    • , Roshan Prizak
    •  & Gašper Tkačik

  • Article
    | Open Access

    Metabolites act as enzyme inhibitors, but their global impact on metabolism has scarcely been considered. Here, the authors generate a human genome-wide metabolite-enzyme inhibition network, and find that inhibition occurs largely due to limited structural diversity of metabolites, leading to a global constraint on metabolism which subcellular compartmentalization minimizes.

    • Mohammad Tauqeer Alam
    • , Viridiana Olin-Sandoval
    •  & Markus Ralser

  • Article
    | Open Access

    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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