Phenotypic screening articles within Nature Communications

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  • Article
    | Open Access

    Assessing cell phenotypes in image-based assays requires solid computational methods for transforming images into quantitative data. Here, the authors present a strategy for learning representations of treatment effects from high-throughput imaging, following a causal interpretation.

    • Nikita Moshkov
    • , Michael Bornholdt
    •  & Juan C. Caicedo

  • Article
    | Open Access

    Cellular senescence is involved in many disease processes but few senolytic compounds are currently known. Here, the authors report the discovery of three senolytics using machine learning models trained solely on published data, with large reductions in drug screening costs.

    • Vanessa Smer-Barreto
    • , Andrea Quintanilla
    •  & Diego A. Oyarzún

  • Article
    | Open Access

    Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

    • Jayme L. Dahlin
    • , Bruce K. Hua
    •  & Bridget K. Wagner

  • Article
    | Open Access

    Sympathetic neurons are affected in familial dysautonomia, a rare disease associated with a mutation in ELP1, but the mechanisms are not fully understood. Here the authors show, using neurons derived from participants with familial dysauotnomia, that spontaneous sympathetic neuron hyperactivity is observed and is associated with norepinephrine transporter deficits.

    • Hsueh-Fu Wu
    • , Wenxin Yu
    •  & Nadja Zeltner

  • Article
    | Open Access

    The heterogeneity underlying cancer organoid phenotypes is not yet well understood. Here, the authors develop an imaging analysis assay for high throughput phenotypic screening of colorectal organoids that allows to define specific morphological changes that occur following different drug treatments.

    • Johannes Betge
    • , Niklas Rindtorff
    •  & Michael Boutros

  • Article
    | Open Access

    Engineered live bacteria could represent a new class of therapeutic treatment for human disease. Here, the authors use a human gut-on-a-chip microfluidics system to characterize an engineered live bacterial therapeutic, designed for the treatment of phenylketonuria, and to construct mathematical models that predict therapeutic strain function in non-human primates.

    • M. Tyler Nelson
    • , Mark R. Charbonneau
    •  & Camilla A. Mauzy

  • Article
    | Open Access

    Epigenetic mechanisms associated with the differentiation state of cancer cells and their heterogeneity influence tumor responses to oncogene-targeted therapies. In this study, the authors perform an epigenetic compound screen and single-cell analysis in BRAF-mutant melanoma cells to identify compounds that block three distinct drug-tolerant epigenetic states associated with either one of the lysine-specific histone demethylases Kdm1a or Kdm4b, or BET proteins.

    • Mehwish Khaliq
    • , Mohan Manikkam
    •  & Mohammad Fallahi-Sichani

  • Article
    | Open Access

    Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound.

    • Veronica Rendo
    • , Ivaylo Stoimenov
    •  & Tobias Sjöblom

  • Article
    | Open Access

    Some anesthetics despite being generally associated with sedation, can also increase brain activity—a phenomenon called paradoxical excitation. The authors identified dozens of compounds that generally decrease neuronal activity, but increase activity in the caudal hindbrain of zebrafish.

    • Matthew N. McCarroll
    • , Leo Gendelev
    •  & David Kokel

  • Article
    | Open Access

    Cryptosporidium infection can cause severe diarrhea with limited treatment options available. Here, Lunde et al. perform a drug repositioning screen with a library of benzoxaboroles and identify AN7973 as potent inhibitor of intracellular parasite development with good efficacy in murine and neonatal dairy calf disease models.

    • Christopher S. Lunde
    • , Erin E. Stebbins
    •  & Christopher D. Huston

  • Article
    | Open Access

    Clostridium difficile causes diarrhea and colitis by producing up to three different protein toxins. Here, Tam et al. show that an anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for toxin entry into host cells, without disrupting the gut microbiota.

    • John Tam
    • , Therwa Hamza
    •  & Roman A. Melnyk

  • Article
    | Open Access

    Detecting proteins and post-translational modifications is important for drug screens, but the number of proteins measurable simultaneously is limited. Here the authors use antibodies tagged with DNA barcodes and high-throughput sequencing to detect up to 70 (phospho-)proteins in stem cells.

    • Jessie A. G. van Buggenum
    • , Jan P. Gerlach
    •  & Klaas W. Mulder

  • Article
    | Open Access

    A bottleneck in developing new anti-fibrosis therapies is the absence of suitable in vitro models that recapitulate key features of fibrogenesis. Here the authors develop a tissue-on-a-chip model of lung fibrosis and test the therapeutic efficacy of two recent FDA-approved drugs.

    • Mohammadnabi Asmani
    • , Sanjana Velumani
    •  & Ruogang Zhao

  • Article
    | Open Access

    Activation of autophagy, via the transcription factor TFEB, is a promising strategy to treat metabolic diseases. Here, the authors report three novel classes of small molecules that promote TFEB nuclear translocation, and provide evidence for the therapeutic efficacy of these compounds in mice and worms.

    • Chensu Wang
    • , Hanspeter Niederstrasser
    •  & Michael A. White

  • Article
    | Open Access

    Chemical screens can identify small molecules that affect biological development, with potential therapeutic value. Here, the authors use a modular approach in a screen in zebrafish embryos, varying concentration, genotype and timing to target segmentation disorders, birth defects that affect the spinal column.

    • Sandra Richter
    • , Ulrike Schulze
    •  & Andrew C. Oates

  • Article
    | Open Access

    Large-scale screens on whole animals could facilitate drug discovery, but are technically challenging. Here, Mondal et al. develop a microfluidic chip combined with an automated imaging platform that enables high-throughput, high-resolution screening of Caenorhabditis elegansdisease models.

    • Sudip Mondal
    • , Evan Hegarty
    •  & Adela Ben-Yakar

  • Article |

    Large-scale screening of animal phenotypes requires automated detection and analysis of complex morphological information. Here, Yanik and colleagues present an imaging system based on optical projection tomography that generates micrometre-resolution 3D images of zebrafish larvae with within tens of seconds per animal.

    • Carlos Pardo-Martin
    • , Amin Allalou
    •  & Mehmet Fatih Yanik

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