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Currently, bioimaging databases cannot be queried by chemical structures that induce the phenotypic effects captured by the image. We present a novel retrieval system based on contrastive learning that is able to identify the chemical structure inducing the phenotype out of $\sim$2,000 candidates with a top-1 accuracy $>$70 times higher than a random baseline.

Recent advances in artificial intelligence, particularly in the field of deep learning, have enabled researchers to create compelling algorithms for medical image analysis. Histological slides of basal cell carcinomas (BCCs), the most frequent skin tumor, are accessed by pathologists on a daily basis and are therefore well suited for automated prescreening by neural networks for the identification of cancerous regions and swift tumor classification. In this proof-of-concept study, we implemented an accurate and intuitively interpretable artificial neural network (ANN) for the detection of BCCs in histological whole-slide images (WSIs). Furthermore, we identified and compared differences in the diagnostic histological features and recognition patterns relevant for machine learning algorithms vs. expert pathologists. An attention-ANN was trained with WSIs of BCCs to identify tumor regions (n = 820). The diagnosis-relevant regions used by the ANN were compared to regions of interest for pathologists, detected by eye-tracking techniques. This ANN accurately identified BCC tumor regions on images of histologic slides (area under the ROC curve: 0.993, 95% CI: 0.990–0.995; sensitivity: 0.965, 95% CI: 0.951–0.979; specificity: 0.910, 95% CI: 0.859–0.960). The ANN implicitly calculated a weight matrix, indicating the regions of a histological image that are important for the prediction of the network. Interestingly, compared to pathologists’ eye-tracking results, machine learning algorithms rely on significantly different recognition patterns for tumor identification (p

Due to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there is an urgent need for novel therapies and drugs. We conducted a large-scale virtual screening for small molecules that are potential CoV-2 inhibitors. To this end, we utilized "ChemAI", a deep neural network trained on more than 220M data points across 3.6M molecules from three public drug-discovery databases. With ChemAI, we screened and ranked one billion molecules from the ZINC database for favourable effects against CoV-2. We then reduced the result to the 30,000 top-ranked compounds, which are readily accessible and purchasable via the ZINC database. Additionally, we screened the DrugBank using ChemAI to allow for drug repurposing, which would be a fast way towards a therapy. We provide these top-ranked compounds of ZINC and DrugBank as a library for further screening with bioassays at https://github.com/ml-jku/sars-cov-inhibitors-chemai., Additional results added. Various corrections to formulations and typos

Predicting the outcome of biological assays based on high-throughput imaging data is a highly promising task in drug discovery since it can tremendously increase hit rates and suggest novel chemical scaffolds. However, end-to-end learning with convolutional neural networks (CNNs) has not been assessed for the task biological assay prediction despite the success of these networks at visual recognition. We compared several CNNs trained directly on high-throughput imaging data to a) CNNs trained on cell-centric crops and to b) the current state-of-the-art: fully connected networks trained on precalculated morphological cell features. The comparison was performed on the Cell Painting data set, the largest publicly available data set of microscopic images of cells with approximately 30,000 compound treatments. We found that CNNs perform significantly better at predicting the outcome of assays than fully connected networks operating on precomputed morphological features of cells. Surprisingly, the best performing method could predict 32% of the 209 biological assays at high predictive performance (AUC > 0.9) indicating that the cell morphology changes contain a large amount of information about compound activities. Our results suggest that many biological assays could be replaced by high-throughput imaging together with convolutional neural networks and that the costly cell segmentation and feature extraction step can be replaced by convolutional neural networks.