Computational models

  • Article
    | Open Access

    The RNA Recognition Motif (RRM) is the most ubiquitous RNA binding domain. Here the authors combined NMR and molecular dynamics simulations and show that the RRM RNA binding surface exists in different states and that a conformational switch of aromatic side-chains fine-tunes sequence specific binding affinities.

    • Nana Diarra dit Konté
    • , Miroslav Krepl
    •  & Frédéric H.-T. Allain
  • Article
    | Open Access

    The pancreas arises from a small population of cells but how individual cells contribute to organ formation is unclear. Here, the authors deconstruct pancreas organogenesis into clonal units, showing that single progenitors give rise to heterogeneous multi-lineage and endocrinogenic single-lineage clones.

    • Hjalte List Larsen
    • , Laura Martín-Coll
    •  & Anne Grapin-Botton
  • Article
    | Open Access

    Early molecules of life likely served both as templates and catalysts, raising the question of how functionally distinct genomes and enzymes arose. Here, the authors show that conflict between evolution at the molecular and cellular levels can drive functional differentiation of the two strands of self-replicating molecules and lead to copy number differences between the two.

    • Nobuto Takeuchi
    • , Paulien Hogeweg
    •  & Kunihiko Kaneko
  • Article
    | Open Access

    Deregulation of E2F family transcription factors is associated with cancer progression and metastasis. Here, the authors construct a map of the regulatory network around the E2F family, and using gene expression profiles, identify tumour type-specific regulatory cores and receptor expression signatures associated with epithelial-mesenchymal transition in bladder and breast cancer.

    • Faiz M. Khan
    • , Stephan Marquardt
    •  & Brigitte M. Pützer
  • Article
    | Open Access

    Cells in the connective tissue are surrounded by a heterogeneous network of biopolymers. Here, the authors investigate how such heterogeneity affects cellular mechanosensing by simulating the deformation response of experimental and modelled biopolymer networks to locally applied forces.

    • Farzan Beroz
    • , Louise M. Jawerth
    •  & Ned S. Wingreen
  • Article
    | Open Access

    Parasitemia has been considered the main determinant of visceral leishmaniasis transmission. By combining imaging, qPCR and experimental xenodiagnoses with mathematical models, Doehl et al. argue that the patchy landscape of parasites in the skin is necessary to explain infectiousness.

    • Johannes S. P. Doehl
    • , Zoe Bright
    •  & Paul M. Kaye
  • Article
    | Open Access

    There are few methods available that can quantify relationships between cell types in tissue images. Here the authors present a quantitative method to evaluate cellular organization, validated in the mouse thymus and spinal cord, called Multitaper Circularly Averaged Spectral Analysis (MiCASA).

    • Andrew Sornborger
    • , Jie Li
    •  & Nancy R. Manley
  • Article
    | Open Access

    The three-dimensional architecture of genome-reduced bacteria is poorly understood. Here the authors combine Hi-C with super-resolution microscopy inMycoplasma pneumoniaeand provide evidence of how supercoiling and local organization influences gene regulation.

    • Marie Trussart
    • , Eva Yus
    •  & Luís Serrano
  • Article
    | Open Access

    Embryonic development is a complex process where genetic and biochemical information direct morphogenesis. Here the authors describe MecaGen, an agent-based model and simulation platform of multicellular development designed to allow a quantitative comparison between simulations and real biological data.

    • Julien Delile
    • , Matthieu Herrmann
    •  & René Doursat
  • Article
    | Open Access

    The cornea is formed of cells that originate from the outer circle of stem cells and that move towards its centre. Here, the authors show that the movement pattern is self-organised, requiring no cues, and that stem cell leakage may account for the presence of stem cells at the centre of the cornea.

    • Erwin P. Lobo
    • , Naomi C. Delic
    •  & J. Guy Lyons
  • Article
    | Open Access

    The prolactin receptor consists of a folded extracellular domain, a transmembrane domain and an intracellular intrinsically disordered domain. Here the authors use a combined experimental and computational approach to obtain a structure of a class I cytokine receptor, the human prolactin receptor.

    • Katrine Bugge
    • , Elena Papaleo
    •  & Birthe B. Kragelund
  • Article
    | Open Access

    Sudden arrhythmic death is a leading cause of mortality, however approaches to identify at-risk patients are of low sensitivity and specificity. Here, the authors develop a personalized approach to assess arrhythmia risk in post-infarction patients based on cardiac imaging and computational modelling that significantly outperforms existing clinical metrics.

    • Hermenegild J. Arevalo
    • , Fijoy Vadakkumpadan
    •  & Natalia A. Trayanova
  • Article
    | Open Access

    The folding of protein domains can occur concomitant with their synthesis, and the rates at which individual codons are translated by the ribosome can affect the folding process. Here the authors present a kinetic model that accurately predicts the probability that a nascent protein domain will co-translationally fold in vivo.

    • Daniel A. Nissley
    • , Ajeet K. Sharma
    •  & Edward P. O’Brien
  • Article
    | Open Access

    TALE proteins are popular tools for genome engineering because they can recognize specific DNA sequences, however off-target effects are a routine problem. Here Rogers and Barrera et al. comprehensively map TALE–DNA interactions to develop a computational model to predict binding specificity.

    • Julia M. Rogers
    • , Luis A. Barrera
    •  & Martha L. Bulyk
  • Article |

    There is currently no consensus on how best to identify and delimit biogeographical regions. Here the authors develop a network-based approach incorporating complex presence–absence patterns that can successfully identify commonly recognized biogeographical regions, and apply it to two large-scale data sets of plants and amphibians.

    • Daril A. Vilhena
    •  & Alexandre Antonelli
  • Article |

    Sequential segmentation in development is best described in vertebrates, where it relies on cell proliferation and shows regular periodicity. Here, the authors show that in the flour beetle segments are added with irregular rate and their elongation during periods of fast growth relies mostly on cell movements.

    • A. Nakamoto
    • , S. D. Hester
    •  & T. A. Williams
  • Article
    | Open Access

    The activity of sensory neurons can be correlated with perceptual decisions and this effect may provide insights into how sensory information is processed during perceptual tasks. Here the authors develop a network model of sensory and decision-making areas and propose that the dynamics across the network hierarchy explains the choice probabilities.

    • Klaus Wimmer
    • , Albert Compte
    •  & Jaime de la Rocha
  • Article
    | Open Access

    Motor learning is characterized by diverse cognitive processes, which lack a unified theoretical framework. Here, Takiyama et al.present a model demonstrating that motor learning is determined by prospective errors, which they test in a specially designed visuomotor adaptation task.

    • Ken Takiyama
    • , Masaya Hirashima
    •  & Daichi Nozaki
  • Article
    | Open Access

    Understanding the epidemiology of malaria transmission between humans and mosquitoes is crucial for successful disease control. Analysing data from an 18-year malaria control programme, Churcher et al. show that decreased parasite prevalence in humans can be found concurrently with an increase in transmission efficiency.

    • Thomas S. Churcher
    • , Jean-François Trape
    •  & Anna Cohuet
  • Article
    | Open Access

    FGFR2 gene variation is associated with breast cancer risk but the molecular mechanism is unknown. Fletcher et al. provide a link between FGFR2 signalling and breast cancer susceptibility by demonstrating that FGFR2 signalling activates the ERa transcriptional network, which drives transcription of risk genes.

    • Michael N. C. Fletcher
    • , Mauro A. A. Castro
    •  & Kerstin B. Meyer
  • Article
    | Open Access

    To describe the biochemical composition of an organism multiple data sets must be combined and this information can then be used forin silico analysis. By combining metabolism and transcription data, Lerman et al. discovered new regulons and improved the gene annotation for the simple organism Thermotoga maritima.

    • Joshua A. Lerman
    • , Daniel R. Hyduke
    •  & Bernhard O. Palsson