Computational biology and bioinformatics

  • Article
    | Open Access

    A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.

    • Warren Winick-Ng
    • , Alexander Kukalev
    •  & Ana Pombo
  • Article |

    Serial femtosecond crystallography (SFX) has provided significant understanding of time-resolved processes of various systems in biology, for example, rhodopsin, which underlies our vision. The approach involves femtosecond-length X-ray pulses directed at protein crystals and has been used to study various photoactive proteins. However, the function of proteins such as rhodopsin requires transcis isomerization of a chromophore, which involves crossing of a conical intersection—a funnel separating potential energy surfaces—at timescales faster than what can be achieved experimentally. Here, Ourmazd and colleagues report a machine learning analysis of SFX data of photoactive yellow protein, which resolves the protein passing through a conical intersection, providing information about the potential energy surfaces involved and achieving time resolution of less than 10 fs. This approach offers an opportunity to understand some of the fastest processes in biology by extracting even more information from SFX datasets.

    • A. Hosseinizadeh
    • , N. Breckwoldt
    •  & A. Ourmazd
  • Article
    | Open Access

    Modelling highlights international travel as the main driver of the introduction of SARS-CoV-2 to Europe and the USA, and suggests that introductions and local transmission may have begun in January 2020.

    • Jessica T. Davis
    • , Matteo Chinazzi
    •  & Alessandro Vespignani
  • Article |

    Focused ion beam scanning electron microscopy (FIB-SEM) combined with deep-learning-based segmentation is used to produce three-dimensional reconstructions of complete cells and tissues, in which up to 35 different organelle classes are annotated.

    • Larissa Heinrich
    • , Davis Bennett
    •  & Destiny Nguyen
  • Article |

    A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

    • Robert Bentham
    • , Kevin Litchfield
    •  & Nicholas McGranahan
  • Article
    | Open Access

    Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

    • Rasa Elmentaite
    • , Natsuhiko Kumasaka
    •  & Sarah A. Teichmann
  • Review Article |

    This review describes the state of spatial transcriptomics technologies and analysis tools that are being used to generate biological insights in diverse areas of biology.

    • Anjali Rao
    • , Dalia Barkley
    •  & Itai Yanai
  • Article
    | Open Access

    AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.

    • Kathryn Tunyasuvunakool
    • , Jonas Adler
    •  & Demis Hassabis
  • Article |

    High-performance hydrodynamic simulations show that the skeletal structure of the deep-sea sponge Euplectella aspergillum reduces the hydrodynamic stresses on it, while possibly being beneficial for feeding and reproduction.

    • Giacomo Falcucci
    • , Giorgio Amati
    •  & Sauro Succi
  • Article
    | Open Access

    AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

    • John Jumper
    • , Richard Evans
    •  & Demis Hassabis
  • Article |

    A proximity-dependent biotinylation technique defines the location of more than 4,000 proteins in a human cell, and almost 36,000 proximal interactions between proteins, including those at the interface of the mitochondria and ER.

    • Christopher D. Go
    • , James D. R. Knight
    •  & Anne-Claude Gingras
  • Article |

    Single-cell and genetic tools are used to characterize the diversity of fibroblasts across healthy and perturbed tissues in mice and humans.

    • Matthew B. Buechler
    • , Rachana N. Pradhan
    •  & Shannon. J. Turley
  • Article |

    A deep-learning-based algorithm uses routinely acquired histology slides to provide a differential diagnosis for the origin of the primary tumour for complicated cases of metastatic tumours and cancers of unknown primary origin.

    • Ming Y. Lu
    • , Tiffany Y. Chen
    •  & Faisal Mahmood
  • Article |

    Lung samples collected soon after death from COVID-19 are used to provide a single-cell atlas of SARS-CoV-2 infection and the ensuing molecular changes.

    • Johannes C. Melms
    • , Jana Biermann
    •  & Benjamin Izar
  • Article |

    In studies using mouse models of psoriasis, a spectrum of innate lymphoid cell types is reconfigured and converges via multiple trajectories on a type 3-like state, demonstrating the range and flexibility of innate lymphoid cell responses in the skin.

    • Piotr Bielecki
    • , Samantha J. Riesenfeld
    •  & Richard A. Flavell
  • Article |

    Influence of the gut microbiome on the human immune system is revealed by systems analysis of vast clinical data from decades of electronic health records paired with massive longitudinal microbiome sequencing.

    • Jonas Schluter
    • , Jonathan U. Peled
    •  & Joao B. Xavier
  • Article |

    The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.

    • Noam Bar
    • , Tal Korem
    •  & Eran Segal
  • Analysis
    | Open Access

    A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal—including 131 previously uncharacterized species—from the Zoonomia Project provides data that support biological discovery, medical research and conservation.

    • Diane P. Genereux
    • , Aitor Serres
    •  & Elinor K. Karlsson
  • Article |

    Transcriptomics, proteomics, single-cell RNA sequencing, population-wide genetic association studies and structure–function analyses provide a picture of how the differential expression of G-protein-coupled receptor isoforms can diversify signalling in different tissues.

    • Maria Marti-Solano
    • , Stephanie E. Crilly
    •  & M. Madan Babu
  • Article |

    The relative risk of COVID-19-associated death for younger individuals (under 65) is consistent across countries and can be used to robustly compare the underlying number of infections in each country.

    • Megan O’Driscoll
    • , Gabriel Ribeiro Dos Santos
    •  & Henrik Salje
  • Article |

    Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

    • Ashot Margaryan
    • , Daniel J. Lawson
    •  & Eske Willerslev
  • Article |

    The building blocks of the nanostructures observed on Drosophila corneas are determined, and then used to create artificial nanostructures with anti-reflective and anti-adhesive properties.

    • Mikhail Kryuchkov
    • , Oleksii Bilousov
    •  & Vladimir L. Katanaev
  • Article |

    An approach for the design of protein pores is demonstrated by the computational design and subsequent experimental expression of both an ion-selective and a large transmembrane pore.

    • Chunfu Xu
    • , Peilong Lu
    •  & David Baker
  • Article |

    The authors find that slow plant growth at low temperatures during winter reduces dilution of the transcription factor NTL8, which allows slow accumulation of NTL8 and thus the gradual increase in transcription of VIN3—a gene involved in memory of cold exposure.

    • Yusheng Zhao
    • , Rea L. Antoniou-Kourounioti
    •  & Martin Howard
  • Article
    | Open Access

    High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

    • Karen H. Miga
    • , Sergey Koren
    •  & Adam M. Phillippy
  • Article |

    Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

    • Alexander G. Ioannidis
    • , Javier Blanco-Portillo
    •  & Andrés Moreno-Estrada