Systems biology

  • Article
    | Open Access

    Despite extensive genetic heterogeneity, nearly half of all multiple myeloma (MM) cases are driven by cyclin D2 (CCND2) over-expression. Here the authors dissect the chromatin landscape of MM to provide insights into the transcriptional regulatory landscape driving MM and divergent transcriptomes corresponding to different MM genetic subtypes.

    • Jaime Alvarez-Benayas
    • , Nikolaos Trasanidis
    •  & Anastasios Karadimitris
  • Article
    | Open Access

    The molecular basis of Alzheimer’s Disease has been obscured by heterogeneity and scarcity of brain gene expression data, which limit effectiveness in complex models. Here, the authors introduce a multi-task deep learning framework to learn generalizable and nuanced relationships between gene expression and neuropathology.

    • Nicasia Beebe-Wang
    • , Safiye Celik
    •  & Su-In Lee
  • Article
    | Open Access

    Complex biomolecular networks are fundamental to the functioning of living systems, both at the cellular level and beyond. In this paper, the authors develop a systems framework to elucidate the interplay of networks and the spatial localisation of network components.

    • Govind Menon
    •  & J. Krishnan
  • Article
    | Open Access

    Cytosolic amino acid concentrations are carefully maintained, but how homeostasis occurs is unclear. Here, the authors show that amino acid transporters primarily determine intracellular amino acid levels and develop a model that predicts a perturbation response similar to experimental data.

    • Gregory Gauthier-Coles
    • , Jade Vennitti
    •  & Stefan Bröer
  • Article
    | Open Access

    Boolean networks allow a simplified representation of interactions. Here, the authors systematically analyze regulation in dozens of biological Boolean networks, finding mathematical regularities that suggest biological systems could be controlled through a relatively small number of components.

    • Enrico Borriello
    •  & Bryan C. Daniels
  • Article
    | Open Access

    Phase separation phenomena have emerged as being of critical importance in biology. Here, using colony formation in C. elegans as model, the authors demonstrate that the basic concepts that underpin phase separation at a molecular level also apply to collective phenomena at the level of a population of organisms.

    • Yuping Chen
    •  & James E. Ferrell Jr.
  • Article
    | Open Access

    Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

    • Noam D. Beckmann
    • , Phillip H. Comella
    •  & Alexander W. Charney
  • Article
    | Open Access

    Formulating metabolic networks mathematically can help researchers study metabolic diseases and optimize the production of industrially important molecules. Here, the authors propose a framework that allows to model eukaryotic metabolism considering gene expression and thermodynamic constraints.

    • Omid Oftadeh
    • , Pierre Salvy
    •  & Vassily Hatzimanikatis
  • Article
    | Open Access

    Storage technology based on DNA is emerging as an information dense and durable medium. Here the authors use machine learning-based encoding and hybridization probes to execute similarity searches in a DNA database.

    • Callista Bee
    • , Yuan-Jyue Chen
    •  & Luis Ceze
  • Article
    | Open Access

    COVID-19 is a critical public health threat, but molecular characterizations of patients’ immunity is still lacking. Here the authors collected blood from patients with various disease severity, and prefiltered to exclude selected comorbidity, to obtain genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles to report a trans-omics landscape.

    • Peng Wu
    • , Dongsheng Chen
    •  & Gang Chen
  • Article
    | Open Access

    The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

    • Katjana Tantale
    • , Encar Garcia-Oliver
    •  & Edouard Bertrand
  • Article
    | Open Access

    An efficient chassis for heterologous expression of biosynthetic gene clusters (BGCs) from Gram-negative bacteria is still unavailable. Here, the authors report rational construction of genome-reduced Burkholderials chassis to facilitate production of a class of new compounds by expressing BGC from Chitinimonas koreensis.

    • Jiaqi Liu
    • , Haibo Zhou
    •  & Xiaoying Bian
  • Article
    | Open Access

    Biological systems are known to behave in optimal ways when poised close to critical points, right on the edge between order and disorder. Here the authors show how this state can be engineered in living cells.

    • Blai Vidiella
    • , Antoni Guillamon
    •  & Ricard Solé
  • Article
    | Open Access

    The blood transcriptome of human subjects can be profiled on an almost routine basis in translational research settings. Here the authors show that a fixed and well-characterized repertoire of transcriptional modules can be employed as a reusable framework for the analysis, visualization and interpretation of such data

    • Matthew C. Altman
    • , Darawan Rinchai
    •  & Damien Chaussabel
  • Article
    | Open Access

    The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.

    • Danyal Akarca
    • , Petra E. Vértes
    •  & Duncan E. Astle
  • Article
    | Open Access

    Synchronizing gene expression across eukaryotic communities presents complex challenges. Here the authors construct a compact synthetic system inspired by bacteria response to antibiotics that robustly converts chemical rhythms into synchronized gene expression across populations.

    • Sara Pérez-García
    • , Mario García-Navarrete
    •  & Krzysztof Wabnik
  • Article
    | Open Access

    The response to neoadjuvant immune checkpoint blockade (ICB) in patients with recurrent gliolastoma multiforme (GBM) has been challenging to interpret. Here the authors develop a tumor analysis framework that reveals molecular similarities between GBM and melanoma and unique patterns of immunosuppression in GBM indicating potential co-targets for neoadjuvant ICB.

    • Yue Lu
    • , Alphonsus H. C. Ng
    •  & James R. Heath
  • Article
    | Open Access

    Controlled actuation is an important aspect of synthetic cellular systems. Here, the authors combine pH responsive DNA origami structures with light triggered proton pump engineered E. coli to trigger a change in pH and control the deformation of giant unilamellar vesicles by simple illumination.

    • Kevin Jahnke
    • , Noah Ritzmann
    •  & Kerstin Göpfrich
  • Article
    | Open Access

    Here the authors use microfluidics and single-cell microscopy to quantify the growth dynamics of individual E. coli cells exposed to nutrient fluctuations with periods as short as 30 seconds, finding that nutrient fluctuations reduce growth rates up to 50% compared to a steady nutrient delivery of equal average concentration, implying that temporal variability is an important parameter in bacterial growth.

    • Jen Nguyen
    • , Vicente Fernandez
    •  & Roman Stocker
  • Article
    | Open Access

    Longitudinal multi-omics measurements are highly valuable in studying heterogeneity in health and disease phenotypes. Here, the authors apply Pareto Task Inference to analyze the clinical lab tests of 3094 individuals and find three wellness states, and one aberrant health state defining this cohort.

    • Anat Zimmer
    • , Yael Korem
    •  & Nathan D. Price
  • Article
    | Open Access

    Regular exercise promotes overall health and prevents non-communicable diseases, but the adaptation mechanisms are unclear. Here, the authors perform a meta-analysis to reveal time-specific patterns of the acute and long-term exercise response in human skeletal muscle, and identify sex- and age-specific changes.

    • David Amar
    • , Malene E. Lindholm
    •  & Euan A. Ashley
  • Article
    | Open Access

    Some patients with COVID-19 fail to clear the viral infection quickly, yet our understanding for the underlying immune characteristics is still lacking. Here the authors use single-cell RNA sequencing and other data form such patients to show that persistent infection is associated with immune suppression and reduced expression of ribosomal protein genes.

    • Bin Yang
    • , Junpeng Fan
    •  & Chaoyang Sun
  • Article
    | Open Access

    A promising strategy to increase product synthesis from bacteria uses inducible systems to switch metabolism to production. Here, the authors use models to show how engineering positive feedback loops into the genetic circuitry creates a switch that requires only temporary induction with a cheap nutrient to switch metabolism irreversibly, and so drastically reduce inducer use and cost.

    • Ahmad A. Mannan
    •  & Declan G. Bates
  • Article
    | Open Access

    Cell based materials production has potential for generating diverse materials with a range of functions. Here, the authors report development of living fabrication of biohybrid semi interpenetrating polymer networks by encapsulating protein producing bacteria within polymer microcapsules.

    • Zhuojun Dai
    • , Xiaoyu Yang
    •  & Lingchong You
  • Article
    | Open Access

    Our understanding of human disease can be improved by integrating the abundance of high throughput biomedical data. Here, the authors use deep learning methods successfully used on images to integrate various types of omics data to improve patient classification and identify disease biomarkers.

    • Tongxin Wang
    • , Wei Shao
    •  & Kun Huang
  • Perspective
    | Open Access

    Effective biological engineering requires the acknowledgement of evolution and its consideration during the design process. In this perspective, the authors present the concept of the evotype to reason about and shape the evolutionary potential of natural and engineered biosystems.

    • Simeon D. Castle
    • , Claire S. Grierson
    •  & Thomas E. Gorochowski
  • Article
    | Open Access

    Microbiomes designed with predictable functions could enable broad applications in health, agriculture and bioprocessing. Here the authors use a model-guided approach to design diverse synthetic human gut communities for production of the health-relevant metabolite butyrate.

    • Ryan L. Clark
    • , Bryce M. Connors
    •  & Ophelia S. Venturelli
  • Article
    | Open Access

    Evolution selects for the fittest but must operate within the realm of the physically possible. Here, the authors present a theoretical framework that allows them to explore how ten abiotic constraints can shape the operation, regulation, and adaptation of metabolism in E. coli.

    • Amir Akbari
    • , James T. Yurkovich
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    How dynamic transcription factors temporally interact to regulate stress survival in yeast is currently unclear. Here the authors integrate single-cell imaging, RNA-seq, and modeling to identify a new cell fate control mechanism mediated by temporal redundancy modulation during yeast stress response.

    • Yan Wu
    • , Jiaqi Wu
    •  & Yihan Lin
  • Article
    | Open Access

    Rewriting genomes allows for complete annotation of gene regulatory elements. Here the authors compare endogenous and rewritten segments of a genome and find extensive transcriptional changes, based on which they formulate design principles that aid in the programming of biological systems.

    • Mariëlle J. F. M. van Kooten
    • , Clio A. Scheidegger
    •  & Beat Christen
  • Article
    | Open Access

    Combining scRNA-seq with spatial information to enable the reconstruction of spatially-resolved cell atlases is challenging for rare cell types. Here the authors present ClumpSeq, an approach for sequencing small clumps of tissue attached cells, and apply it to establish spatial atlases for all secretory cell types in the small intestine.

    • Rita Manco
    • , Inna Averbukh
    •  & Shalev Itzkovitz
  • Article
    | Open Access

    The functional consequences of variation in human regulatory DNA depend on the local chromatin environment and the cell/tissue context. Here the authors use highly diverged hybrid mice to study genetic effects on DNA accessibility in vivo across multiple cell and tissue types.

    • Jessica M. Halow
    • , Rachel Byron
    •  & Matthew T. Maurano