Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Glycolytic regulator PFKFB3 is a key player in vessel sprouting. Here the authors develop a computational model predicting that PFKFB3 drives endothelial cell rearrangement during vessel sprouting by promoting filopodia formation and reducing intercellular adhesion, and empirically validate this prediction.

    • Bert Cruys
    • , Brian W. Wong
    •  & Peter Carmeliet

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Many microbial lineages have not yet been cultured, which hampers our understanding of their physiology. Here, Wurch et al. use single-cell genomics to infer cultivation conditions for the isolation of a tiny ectosymbiotic nanoarchaeon and its crenarchaeota host from a geothermal spring.

    • Louie Wurch
    • , Richard J. Giannone
    •  & Mircea Podar

  • Article
    | Open Access

    Proteomic technologies are capable of identifying thousands of proteins in biological samples, but biomarker applications are lagging. Here the authors use Multiple Reaction Monitoring Mass Spectrometry to delineate peptide signatures that accurately distinguish between defined prostate cancer patient risk groups.

    • Yunee Kim
    • , Jouhyun Jeon
    •  & Thomas Kislinger

  • Article
    | Open Access

    Analysis of network structure is usually based on knowledge of connections alone, ignoring additional information such as gender or age of individuals in social networks. Here the authors devise an approach that incorporates such metadata and uses it to improve the detection of network communities.

    • M. E. J. Newman
    •  & Aaron Clauset

  • Article
    | Open Access

    Identifying and annotating functional elements in the human genome remains a challenging but important task. Here the authors propose a priority annotation score to rank identifications and suggest how proteogenomics evidence can be interpreted and what additional information substantiates protein-coding potential for annotation.

    • James C. Wright
    • , Jonathan Mudge
    •  & Jennifer Harrow

  • Article
    | Open Access

    Bacteria of the genus Streptomyces produce a great variety of natural products, the biosynthesis of which is subject to complex regulatory networks. Here the authors present a high-resolution, genome-wide analysis of the transcriptome and translatome of Streptomyces coelicolorunder various growth conditions.

    • Yujin Jeong
    • , Ji-Nu Kim
    •  & Byung-Kwan Cho

  • Article
    | Open Access

    Protein nanotechnology for the fabrication of protein-based nanoscale devices is gaining momentum but assembling well-defined three-dimensional shapes is still challenging. Here, the authors use an existing prefoldin assembled system to design a template for the construction of geometrically constrained structures.

    • Dominic J. Glover
    • , Lars Giger
    •  & Douglas S. Clark

  • Article
    | Open Access

    Stochastic reaction-diffusion systems are used for modelling spatial dynamics in many disciplines, but parameter inference and model selection remain challenging. Here the authors offer a solution enabled by a connection between reaction-diffusion and the well-studied spatio-temporal Cox processes.

    • David Schnoerr
    • , Ramon Grima
    •  & Guido Sanguinetti

  • Article
    | Open Access

    Mouse digit patterning is controlled by a Turing network of Bmp, Sox9, and Wnt. Here, Onimaru et al. show that fin patterning in the catshark, Scyliorhinus canicula, is controlled by the same network with a different spatial organization; thus, the Turing network is deeply conserved in limb development.

    • Koh Onimaru
    • , Luciano Marcon
    •  & James Sharpe

  • Article
    | Open Access

    A fundamental question in evolutionary biology is how complex innovations requiring multiple genetic changes arise. Here the authors provide lines of evidence that changing environments facilitate the adaptive evolution of complex metabolic innovations via stepwise acquisition of single reactions.

    • Balázs Szappanos
    • , Jonathan Fritzemeier
    •  & Balázs Papp

  • Article
    | Open Access

    Research on the interactions between the gut microbiota and human cells would greatly benefit from improved in vitro models. Here, Shah et al. present a modular microfluidics-based model that allows co-culture of human and microbial cells followed by 'omic' molecular analyses of the two cell contingents.

    • Pranjul Shah
    • , Joëlle V. Fritz
    •  & Paul Wilmes

  • Article
    | Open Access

    We know little about the effect of relationships between species on the assembly of microbial communities. Here the authors map pairwise invasion relations between bacteria and find that instead of one strain dominating, inhibitory interactions mean that often neither strain can invade the other.

    • Erik S. Wright
    •  & Kalin H. Vetsigian

  • Article
    | Open Access

    Complex networks, including physical, biological and social systems are ubiquitous, but understanding of how to control them is elusive. Here Wang et al. develop a framework based on the concept of attractor networks to facilitate the study of controllability of nonlinear dynamics in complex systems.

    • Le-Zhi Wang
    • , Ri-Qi Su
    •  & Ying-Cheng Lai

  • Article
    | Open Access

    The use of specific small molecule inhibitors can contribute to the study of kinesins' cellular functions. Here the authors develop a chemical-genetic approach to engineer kinesin motors that can be efficiently inhibited upon addition of cell-permeable molecules.

    • Martin F. Engelke
    • , Michael Winding
    •  & Kristen J. Verhey

  • Article
    | Open Access

    Sigma factors are regulatory proteins that reprogram the bacterial RNA polymerase in response to stress conditions to transcribe certain genes, including those for other sigma factors. Here, Chauhan et al. describe the complete sigma factor regulatory network of the pathogen Mycobacterium tuberculosis.

    • Rinki Chauhan
    • , Janani Ravi
    •  & Maria Laura Gennaro

  • Article
    | Open Access

    Early cells likely consisted of fatty acid vesicles enclosing magnesium-dependent ribozymes. Here, the authors show that fatty acid derivatives can form vesicles that, unlike those formed from only unmodified fatty acids, are stable in the presence of magnesium and could support ribozyme catalysis.

    • Katarzyna P. Adamala
    • , Aaron E. Engelhart
    •  & Jack W. Szostak

  • Article
    | Open Access

    Heart contraction, which is decreased in disease, is determined by Ca2+binding to troponin C. Here, the authors combine a protein engineering approach with gene therapy to modulate heart contractility in mice with the use of rationally designed Troponin C variants, suggesting a new therapy for diseased hearts.

    • Vikram Shettigar
    • , Bo Zhang
    •  & Jonathan P. Davis

  • Article
    | Open Access

    Analysis of RNAi screens is a multi-step process requiring the sequential use of several unrelated resources. Here the authors generate an online resource integrating RNAi analytic tools and filters into a seamless workflow, which improves the specificity, selectivity and reproducibility of the results.

    • Bhaskar Dutta
    • , Alaleh Azhir
    •  & Iain D. C. Fraser

  • Article
    | Open Access

    Progress in drug discovery can be hampered by a limited exploration of chemical space and the difficulty in assessing the full range of drug candidates’ effects on living cells. Here the authors describe a cell-based assay to distinguish between off-target and specific effects of candidate compounds targeting micro RNAs.

    • Benjamin Haefliger
    • , Laura Prochazka
    •  & Yaakov Benenson

  • Article
    | Open Access

    TATA boxes in gene promoters are associated with high level of cell-to-cell variation in gene expression. Through integration of multiple data sets, the authors now provide insights into how the interactions of TBP with DNA and other proteins can lead to noisy expression.

    • Charles N. J. Ravarani
    • , Guilhem Chalancon
    •  & M. Madan Babu

  • Article
    | Open Access

    Attempts to predict novel use for existing drugs rarely consider information on the impact on the genes perturbed in a given disease. Here, the authors present a novel network-based drug-disease proximity measure that provides insight on gene specific therapeutic effect of drugs and may facilitate drug repurposing.

    • Emre Guney
    • , Jörg Menche
    •  & Albert-László Barábasi

  • Article
    | Open Access

    While ERK signalling can produce switch-like cell behaviour, phosphorylation of ERK increases linearly with extracellular signals. Here, the authors solve this seeming contradiction by showing that nuclear translocation of ERK behaves in a switch-like manner and is controlled by ERK activity.

    • Yuki Shindo
    • , Kazunari Iwamoto
    •  & Koichi Takahashi

  • Article
    | Open Access

    Sepsis can lead to multiple organ failure that could potentially be reflected by change in plasma protein abundance. Here the authors describe a proteomics strategy that allows the determination of plasma proteins tissue origin in a quantitative manner for use as biomarkers—illustrated in a mouse model of sepsis.

    • Erik Malmström
    • , Ola Kilsgård
    •  & Johan Malmström

  • Article
    | Open Access

    Breast cancers have been extensively studied at the genomic and transcriptomic levels in the hope of tailoring therapeutic regimens. Here the authors generate deep coverage proteomes from several clinical breast cancer samples, and use machine learning techniques to uncover biological processes altered in specific cancer subtypes.

    • Stefka Tyanova
    • , Reidar Albrechtsen
    •  & Tamar Geiger

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Cell-to-cell variability in viral infection means that cell population measurements may not be an accurate representation of the process. Using both experimental and modelling approaches the authors confirm this notion showing that influenza virus infections are variable processes affected by intrinsic and extrinsic noise.

    • Frank S. Heldt
    • , Sascha Y. Kupke
    •  & Timo Frensing

  • Article
    | Open Access

    Magnetic manipulation of biological systems requires the development of improved molecular handles. Here the authors isolate ferritin mutants with enhanced biomineralization from a yeast genetic screen and show their application to cell separation, multiscale imaging, and construction of sensors.

    • Yuri Matsumoto
    • , Ritchie Chen
    •  & Alan Jasanoff

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The biochemical pathways of central carbon metabolism are highly conserved across all domains of life. Here, Courtet al. use a computational approach to test all possible pathways of glycolysis and gluconeogenesis and find that the existing trunk pathways may represent a maximal flux solution selected for during evolution.

    • Steven J. Court
    • , Bartlomiej Waclaw
    •  & Rosalind J. Allen

  • Article
    | Open Access

    The prolonged presence of cytokines is necessary to produce a robust pro-inflammatory response through the activation of p38 MAPK. Here, Tomidaet al. show that asynchronous oscillatory activation of p38 MAPK occurs at the single-cell level and is necessary for the proper expression of pro-inflammatory genes.

    • Taichiro Tomida
    • , Mutsuhiro Takekawa
    •  & Haruo Saito

  • Article
    | Open Access

    Cells respond to increasing concentrations of EGF by altering the balance between EGFR phosphorylation and ubiquitination. Here the authors show that the establishment of an EGFR signaling threshold requires both a multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR.

    • Fabrizio Capuani
    • , Alexia Conte
    •  & Andrea Ciliberto

  • Article
    | Open Access

    In metalloproteins, a metal cofactor participates in the formation of the correct fold. Here the authors demonstrate—using single molecule force spectroscopy and the native copper centre as an embedded internal reporter—that the blue-copper proteins azurin and plastocyanin unfold via two independent competing pathways under force.

    • Amy E. M. Beedle
    • , Ainhoa Lezamiz
    •  & Sergi Garcia-Manyes

  • Article
    | Open Access

    Protein kinases expressed by the malaria parasite Plasmodium falciparum represent potentially valuable drug targets. Alam et al. identify proteins whose phosphorylation is dependent on the kinase PfPKG, revealing a regulatory network controlling parasite egress from red blood cells and calcium signalling.

    • Mahmood M. Alam
    • , Lev Solyakov
    •  & Andrew B. Tobin

  • Article |

    Allostery, communication between distant parts of a protein, is a key element of enzyme catalysis. Here the authors combine existing experimental data with molecular dynamics simulations and Markov state models to provide insight into the mechanism of ligand-induced allostery within the cyclicnucleotide-binding domain of protein kinase A.

    • Robert D. Malmstrom
    • , Alexandr P. Kornev
    •  & Rommie E. Amaro

  • Article
    | Open Access

    Mutated tRNA synthetases can incorporate non-canonical amino acids into proteins. Erdmann et al. exploit this property to metabolically label newly synthesized proteins in selected cell types in Drosophila, and demonstrate their detection using proteomics (BONCAT) and fluorescence imaging (FUNCAT).

    • Ines Erdmann
    • , Kathrin Marter
    •  & Daniela C. Dieterich

  • Article
    | Open Access

    Tryptic digestion of SUMOylated proteins generates large peptides, rendering proteomic characterisation of this post-translational modification particularly challenging unless mutant SUMO is used. Hendriks et al.present a method that allows the quantitative identification of wild-type SUMO sites.

    • Ivo A. Hendriks
    • , Rochelle C. D’Souza
    •  & Alfred C. O. Vertegaal

  • Article
    | Open Access

    Proteins are sometimes implicated in separate and seemingly unrelated processes, so called moonlighting functions. Here the authors use bioinformatics tools to identify extreme multifunctional proteins and define a signature of extreme multifunctionality.

    • Charles E. Chapple
    • , Benoit Robisson
    •  & Christine Brun

  • Article
    | Open Access

    Cells constantly integrate information from multiple stimuli. By considering every possible means by which two stimuli can interact, Cappuccio et al. define 10 interaction modes and demonstrate their preferential use by dendritic cells responding to different combinations of microbial and host inflammatory cues.

    • Antonio Cappuccio
    • , Raphaël Zollinger
    •  & Vassili Soumelis

  • Article
    | Open Access

    Measuring phosphorylation stoichiometry on a proteomic scale remains a challenge. Tsai et al. develop a technique to measure the basal level of phosphorylation stoichiometry in a single human phosphoproteome and identify molecular changes associated with gefitinib resistance in lung cancer cells.

    • Chia-Feng Tsai
    • , Yi-Ting Wang
    •  & Yu-Ju Chen

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