Discovering highly potent antimicrobial peptides with deep generative model HydrAMP.

Antimicrobial peptides emerge as compounds that can alleviate the global health hazard of antimicrobial resistance, prompting a need for novel computational approaches to peptide generation. Here, we propose HydrAMP, a conditional variational autoencoder that learns lower-dimensional, continuous representation of peptides and captures their antimicrobial properties. The model disentangles the learnt representation of a peptide from its antimicrobial conditions and leverages parameter-controlled creativity. HydrAMP is the first model that is directly optimized for diverse tasks, including unconstrained and analogue generation and outperforms other approaches in these tasks. An additional preselection procedure based on ranking of generated peptides and molecular dynamics simulations increases experimental validation rate. Wet-lab experiments on five bacterial strains confirm high activity of nine peptides generated as analogues of clinically relevant prototypes, as well as six analogues of an inactive peptide. HydrAMP enables generation of diverse and potent peptides, making a step towards resolving the antimicrobial resistance crisis.

ARA: accurate, reliable and active histopathological image classification framework with Bayesian deep learning.

Machine learning algorithms hold the promise to effectively automate the analysis of histopathological images that are routinely generated in clinical practice. Any machine learning method used in the clinical diagnostic process has to be extremely accurate and, ideally, provide a measure of uncertainty for its predictions. Such accurate and reliable classifiers need enough labelled data for training, which requires time-consuming and costly manual annotation by pathologists. Thus, it is critical to minimise the amount of data needed to reach the desired accuracy by maximising the efficiency of training. We propose an accurate, reliable and active (ARA) image classification framework and introduce a new Bayesian Convolutional Neural Network (ARA-CNN) for classifying histopathological images of colorectal cancer. The model achieves exceptional classification accuracy, outperforming other models trained on the same dataset. The network outputs an uncertainty measurement for each tested image. We show that uncertainty measures can be used to detect mislabelled training samples and can be employed in an efficient active learning workflow. Using a variational dropout-based entropy measure of uncertainty in the workflow speeds up the learning process by roughly 45%. Finally, we utilise our model to segment whole-slide images of colorectal tissue and compute segmentation-based spatial statistics.