Functional clustering

  • Article
    | Open Access

    Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.

    • Sokratis Kariotis
    • , Emmanuel Jammeh
    •  & Gwen Schotte
  • Article
    | Open Access

    While transcriptomics have enhanced our understanding for cancer, spatial transcriptomics enable the characterisation of cellular interactions. Here, the authors integrate single cell data with spatial information for HER2 + tumours and develop tools for the prediction of interactions between tumour-infiltrating cells.

    • Alma Andersson
    • , Ludvig Larsson
    •  & Joakim Lundeberg
  • Article
    | Open Access

    Advances in omics approaches could enable quantitative predictions of microbial functional composition. Here the authors re-analyze 885 metagenome-assembled genomes from Tara Oceans, and use a network approach to quantify protein functional clusters and explore their biogeography.

    • Emile Faure
    • , Sakina-Dorothée Ayata
    •  & Lucie Bittner
  • Article
    | Open Access

    It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.

    • Pearl Quijada
    • , Michael A. Trembley
    •  & Eric M. Small
  • Article
    | Open Access

    Few studies have provided functional analysis of the epigenetic landscape in the regenerating liver. Here the authors define chromatin states in the quiescent vs. regenerating mouse liver through integration of genome wide profiles of DNA methylation, histone modifications, and chromatin accessibility, identifying H3K27me3 as an epigenetic mark conferring regenerative potential.

    • Chi Zhang
    • , Filippo Macchi
    •  & Kirsten C. Sadler
  • Article
    | Open Access

    High-grade serous ovarian cancer (HGSOC) is prone to developing resistance to treatment. Here, the authors use single-cell RNA-seq and an analysis of archetypes, and find that shifts in metabolism and proliferation are associated with the response to treatment and clonal heterogeneity in HGSOC.

    • Aritro Nath
    • , Patrick A. Cosgrove
    •  & Andrea H. Bild
  • Article
    | Open Access

    Our understanding of the function of many transcripts is still incomplete, limiting the interpretability of transcriptomic data. Here the authors use consensus-independent component analysis, together with a guilt-by-association approach, to improve the prediction of gene function.

    • Carlos G. Urzúa-Traslaviña
    • , Vincent C. Leeuwenburgh
    •  & Rudolf S. N. Fehrmann
  • Article
    | Open Access

    Genomic prediction of phenotype may be improved by using DNA mutations with functional, evolutionary, and pleiotropic consequences. Here the authors describe a method for genome-wide fine-mapping of QTLs and develop a genotyping array for improved prediction of genetic values for cattle traits.

    • Ruidong Xiang
    • , Iona M. MacLeod
    •  & Michael E. Goddard
  • Article
    | Open Access

    Chronic lung diseases are characterized by molecular and cellular composition changes. Here the authors use single-cell RNA sequencing to map cell type-specific changes in human tracheal epithelium related to smoking, and to provide evidence for a tuft-like progenitor for pulmonary neuroendocrine cells and ionocytes.

    • Katherine C. Goldfarbmuren
    • , Nathan D. Jackson
    •  & Max A. Seibold
  • Article
    | Open Access

    Single-cell ATAC-seq data is challenging to analyse for reasons such as high dimensionality and sparsity. Here, the authors develop SCALE, a deep learning method that leverages latent feature extraction for various tasks of scATACseq data analysis.

    • Lei Xiong
    • , Kui Xu
    •  & Qiangfeng Cliff Zhang
  • Article
    | Open Access

    In the ovary, follicular degeneration occurs after folliculogenesis, with one dominant follicle reaching maturity every month. Here, by performing single cell RNA-seq of adult human follicles, the authors identify subclasses of granulosa and theca cell lineages, which correlate with the growth or degeneration of the follicles.

    • X. Fan
    • , M. Bialecka
    •  & S. M. Chuva de Sousa Lopes
  • Article
    | Open Access

    Cardiac progenitor cells (CPCs) form cardiomyocytes, pericytes, smooth muscle and endothelial cells during embryonic development. Here, the authors characterize mouse CPCs marked by Nkx2.5 and Isl1 from E7.5 to E9.5 by single cell RNA-seq and ATAC-seq, showing fate transitions involve distinct open chromatin state.

    • Guangshuai Jia
    • , Jens Preussner
    •  & Thomas Braun
  • Article
    | Open Access

    Barrett’s oesophagus is associated with an increased risk of oseophageal cancer, but its cell of origin is unclear. Here the authors show, using single-cell RNA sequencing of biopsies from six patients and two unaffected subjects, that cells in Barrett’s oesophagus show a transcriptional profile that is similar to that of cells in oesophageal submucosal glands.

    • Richard Peter Owen
    • , Michael Joseph White
    •  & Xin Lu
  • Article
    | Open Access

    Cation/proton antiporters (CPAs) play a major role in maintaining living cells’ homeostasis and are divided in two main groups: CPA1 and CPA2. Here authors use a comprehensive evolutionary analysis of 6537 representative CPAs and reveal a sequence motif that determines central phenotypic characteristics.

    • Gal Masrati
    • , Manish Dwivedi
    •  & Nir Ben-Tal
  • Article
    | Open Access

    Triple-negative breast cancer is highly heterogeneous and aggressive. Here, the authors utilise single-cell RNA sequencing to investigate this heterogeneity, and discover a subpopulation of cells associated with metastasis and treatment resistance signatures, and linked to long term survival outcomes.

    • Mihriban Karaayvaz
    • , Simona Cristea
    •  & Leif W. Ellisen
  • Article
    | Open Access

    Billions of metagenomic and genomic sequences fill up public datasets, which makes similarity clustering an important and time-critical analysis step. Here, the authors develop Linclust, an algorithm with linear time complexity that can cluster over a billion sequences within hours on a single server.

    • Martin Steinegger
    •  & Johannes Söding
  • Article
    | Open Access

    Single cell ATAC-seq (scATAC-seq) data reveals cellular level epigenetic heterogeneity but its application in delineating distinct subpopulations is still challenging. Here, the authors develop scABC, a statistical method for unsupervised clustering of scATAC-seq data and identification of open chromatin regions specific to cell identity.

    • Mahdi Zamanighomi
    • , Zhixiang Lin
    •  & Wing Hung Wong
  • Article
    | Open Access

    Synovial fibroblasts are thought to be central mediators of joint destruction in rheumatoid arthritis (RA). Here the authors use single-cell transcriptomics and flow cytometry to identify synovial fibroblast subsets that are expanded and display distinct tissue distribution and function in patients with RA.

    • Fumitaka Mizoguchi
    • , Kamil Slowikowski
    •  & Michael B. Brenner
  • Article
    | Open Access

    Ligand-induced biased signaling is thought to result in part from ligand-specific receptor conformations that cause the engagement of distinct effectors. Here the authors trace and evaluate the impact of mutations of the β2–adrenergic receptor on multiple signaling outputs to provide structural-level insight into the determinants of GPCR functional selectivity.

    • Anne-Marie Schönegge
    • , Jonathan Gallion
    •  & Michel Bouvier
  • Article
    | Open Access

    In eukaryotic cells, the ubiquitylation system regulates several cellular processes central to protein homoeostasis. Here the authors demonstrate the existence of an eukaryotic-like ubiquitylation cascade requiring E1, E2 and E3-like enzymes in the archaeon C. subterraneum, shedding light on the evolution of the ubiquitin-proteasome system.

    • Rory Hennell James
    • , Eva F. Caceres
    •  & Nicholas P. Robinson
  • Article
    | Open Access

    Hepatocellular carcinoma is known to harbour numerous genomic and epigenomic aberrations, driving transcriptomic deregulation. Here, the authors integrate genomic, epigenomic, and expression data to reveal three prognostic subtypes, providing insight to the pathobiology of hepatocellular carcinoma.

    • Hyun Goo Woo
    • , Ji-Hye Choi
    •  & Yoon Jun Kim
  • Article
    | Open Access

    Formation and reinforcement of E-cadherin-mediated adhesion depends on intracellular trafficking and interactions with the actin cytoskeleton, but how these are coordinated is not known. Here the authors conduct a focused phenotypic screen to identify new pathways regulating cell–cell junction homeostasis.

    • J. C. Erasmus
    • , S. Bruche
    •  & V. M. M. Braga