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Ravn, K.

Publications and source records attributed to Ravn, K..

3 recordsLinked to original sources

Unsupervised learning of multi-omics data enables disease risk prediction in the UK Biobank

The size and complexity of biomedical datasets continue to grow, driving the development of methods that reduce dimensionality while preserving biological signals. Yet, when deep learning is applied to such data, the impact of preprocessing choices and dataset properties on model behavior is often overlooked. Here, we applied our framework Multi-Omics Variational autoEncoder (MOVE) to multiomics data from 452,026 UK Biobank participants, aiming to both evaluate the power of the learned representations for disease risk prediction and critically analyze how non-biological factors, like dataset properties and preprocessing decisions, can shape and influence the results. We show that reducing the dimensionality of the data by a factor of 80 still yields comparable prediction performance across 15 different diseases. We further demonstrate how dataset properties and preprocessing choices impact the model performance, latent representation and downstream results, and our findings strongly underline the need for thorough analysis and understanding of a models behavior before drawing conclusions from its results.

bioinformatics↗

A versatile Halo- and SNAP-tagged BMP/TGFβ receptor library for quantification of cell surface ligand binding

The TGF{beta} superfamily of secreted growth factors comprises more than 30 members including TGF{beta}s, BMPs and Activins. While all TGF{beta} superfamily members signal through heteromeric receptor complexes to regulate a plethora of developmental and homeostatic processes, each ligand possesses a unique affinity towards a subset of BMP and TGF{beta} type I and type II receptors. Whereas the Activin and TGF{beta} class display a higher affinity towards type II receptors, BMPs and GDFs preferentially bind to type I receptors. Sofar, the lack of specific antibodies and chemical biology tools hampered simultaneous testing of ligand binding towards all BMP and TGF{beta} receptors. Here we present a N-terminally Halo- and SNAP-tagged TGF{beta}/BMP receptor library to visualize the receptor complexes in dual color. In combination with novel fluorescently labeled TGF{beta} superfamily ligands, we established a Ligand Surface Binding Assay (LSBA) for optical quantification of receptor-dependent growth factor binding for Activin A, TGF{beta}1 and BMP9 in a cellular context. We confirm ligand-receptor interface specificity by identifying BMPR2- or ALK2-mutants that switch from a low-affinity Activin A- or BMP9-receptor to a high-affinity receptor, respectively.

cell biology↗

Organoid culture media containing growth factors of defined cellular activity

The media components necessary for deriving and sustaining organoids from a number of epithelial tissues such as prostate, colon, gastric, liver, pancreas, and others have been established (1). Critical components of organoid media formulations are a set of growth factors that include EGF, R-spondins and BMP signalling antagonists such as Noggin or Gremlin. The practical limitation to organoid culture and the development of new applications for the technology is the use of defined cellular activities of growth factors in media formulations, in particular Noggin/Gremlin 1 and R-spondin 1. Here we report the production of highly pure recombinant Gremlin 1 and R-spondin 1 from bacterial expression and their use for culturing organoids. We detail the workflow for their purification, determination of cellular activity, quality control and their formulation in organoid media. The protocols we provide for generation of precisely formulated, cost-effective, organoid media of defined cellular activity will enable broader access to organoid technology and engender the development of novel applications.

cell biology↗