Publications by authors named "R A Senft"

Cell Painting images offer valuable insights into a cell's state and enable many biological applications, but publicly available arrayed datasets only include hundreds of genes perturbed. The JUMP Cell Painting Consortium perturbed roughly 75% of the protein-coding genome in human U-2 OS cells, generating a rich resource of single-cell images and extracted features. These profiles capture the phenotypic impacts of perturbing 15,243 human genes, including overexpressing 12,609 genes (using open reading frames) and knocking out 7,975 genes (using CRISPR-Cas9).

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Advances in high-throughput microscopy have enabled the rapid acquisition of large numbers of high-content microscopy images. Next, whether by deep learning or classical algorithms, image analysis pipelines commonly produce single-cell features. To process these single cells for downstream applications, we present Pycytominer, a user-friendly, open-source Python package that implements the bioinformatics steps key to image-based profiling.

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Article Synopsis
  • Widespread sequencing has identified thousands of missense variants linked to diseases, creating a challenge in assessing their functional impact at scale.
  • A new high-throughput imaging platform was developed to evaluate the effects of 3,448 missense variants across over 1,000 genes, revealing that mislocalization of proteins is a frequent outcome.
  • Mislocalization affects about one-sixth of pathogenic variants and is mainly caused by issues with protein stability and membrane insertion, which can influence disease severity and help interpret uncertain variants.
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We herein describe a postdoctoral training program designed to train biologists with microscopy experience in bioimage analysis. We detail the rationale behind the program, the various components of the training program, and outcomes in terms of works produced and the career effects on past participants. We analyze the results of an anonymous survey distributed to past and present participants, indicating overall high value of all 12 rated aspects of the program, but significant heterogeneity in which aspects were most important to each participant.

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Changes in the amount of daylight (photoperiod) alter physiology and behaviour. Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders and metabolic syndromes. The circadian rhythm circuitry is implicated in such responses, yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change.

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