Publications by authors named "Michael Bornholdt"

In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles' high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise.

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Measuring the phenotypic effect of treatments on cells through imaging assays is an efficient and powerful way of studying cell biology, and requires computational methods for transforming images into quantitative data. Here, we present an improved strategy for learning representations of treatment effects from high-throughput imaging, following a causal interpretation. We use weakly supervised learning for modeling associations between images and treatments, and show that it encodes both confounding factors and phenotypic features in the learned representation.

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Advances in high-throughput microscopy have enabled the rapid acquisition of large numbers of high-content microscopy images. Whether by deep learning or classical algorithms, image analysis pipelines then 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, known as "image-based profiling".

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Morphological and gene expression profiling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to profile gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state.

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The objective of this study was to develop instant thin-layer chromatography (ITLC) conditions for the determination of radiochemical purity of Ga-DOTATATE in a shorter time period than those stated in the NETSPOT (Advanced Accelerator Applications, Saint-Genis-Pouilly, France; AAA) kit package insert (PI). A faster ITLC system is needed to reduce the 48- to 50-min development time so that more radioactivity is available for single patient use and wait times are shorter in the event of kit failure. Variations of the PI mobile system were evaluated with microfiber chromatography paper impregnated with silica gel (ITLC-SG).

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