Genome-wide CRISPR screens are an effective discovery tool for genes that underlie diverse cellular mechanisms that can be scored through cell fitness. Loss-of-function screens are particularly challenging compared to gain-of-function because of the limited dynamic range of decreased sgRNA sequence detection. Here we describe Guide-Only control CRISPR (GO-CRISPR), an improved loss-of-function screening workflow, and its companion software package, Toolset for the Ranked Analysis of GO-CRISPR Screens (TRACS).
View Article and Find Full Text PDFHow does the brain track and process rapidly changing sensory information? Current computational accounts suggest that our sensations and decisions arise from the intricate interplay between bottom-up sensory signals and constantly changing expectations regarding the statistics of the surrounding world. A significant focus of recent research is determining which statistical properties are tracked by the brain as it monitors the rapid progression of sensory information. Here, by combining EEG (three experiments N ≥ 22 each) and computational modelling, we examined how the brain processes rapid and stochastic sound sequences that simulate key aspects of dynamic sensory environments.
View Article and Find Full Text PDFFibrosing interstitial lung diseases (ILDs) encompass a diverse range of scarring disorders that lead to progressive lung failure. Previous gene expression profiling studies focused on idiopathic pulmonary fibrosis (IPF) and bulk tissue samples. We employed digital spatial profiling to gain new insights into the spatial resolution of gene expression across distinct lung microenvironments (LMEs) in IPF, chronic hypersensitivity pneumonitis (CHP) and non-specific interstitial pneumonia (NSIP).
View Article and Find Full Text PDFHumans and other animals develop remarkable behavioral specializations for identifying, differentiating, and acting on classes of ecologically important signals. Ultimately, this expertise is flexible enough to support diverse perceptual judgments: a voice, for example, simultaneously conveys what a talker says as well as myriad cues about her identity and state. Mature perception across complex signals thus involves both discovering and learning regularities that best inform diverse perceptual judgments, and weighting this information flexibly as task demands change.
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