A clustering and graph deep learning-based framework for COVID-19 drug repurposing

Drug repurposing (or repositioning) is the process of finding new therapeutic uses for drugs already approved by drug regulatory authorities (e.g., the Food and Drug Administration (FDA) and Therapeutic Goods Administration (TGA)) for other diseases. This involves analyzing the interactions between different biological entities, such as drug targets (genes/proteins and biological pathways) and drug properties, to discover novel drug-target or drug-disease relations. Artificial intelligence methods such as machine learning and deep learning have successfully analyzed complex heterogeneous data in the biomedical domain and have also been used for drug repurposing. This study presents a novel unsupervised machine learning framework that utilizes a graph-based autoencoder for multi-feature type clustering on heterogeneous drug data. The dataset consists of 438 drugs, of which 224 are under clinical trials for COVID-19 (category A). The rest are systematically filtered to ensure the safety and efficacy of the treatment (category B). The framework solely relies on reported drug data, including its pharmacological properties, chemical/physical properties, interaction with the host, and efficacy in different publicly available COVID-19 assays. Our machine-learning framework reveals three clusters of interest and provides recommendations featuring the top 15 drugs for COVID-19 drug repurposing, which were shortlisted based on the predicted clusters that were dominated by category A drugs. The anti-COVID efficacy of the drugs should be verified by experimental studies. Our framework can be extended to support other datasets and drug repurposing studies, given open-source code and data availability.

Bounding Box Priors for Cell Detection with Point Annotations

The size of an individual cell type, such as a red blood cell, does not vary much among humans. We use this knowledge as a prior for classifying and detecting cells in images with only a few ground truth bounding box annotations, while most of the cells are annotated with points. This setting leads to weakly semi-supervised learning. We propose replacing points with either stochastic (ST) boxes or bounding box predictions during the training process. The proposed "mean-IOU" ST box maximizes the overlap with all the boxes belonging to the sample space with a class-specific approximated prior probability distribution of bounding boxes. Our method trains with both box- and point-labelled images in conjunction, unlike the existing methods, which train first with box- and then point-labelled images. In the most challenging setting, when only 5% images are box-labelled, quantitative experiments on a urine dataset show that our one-stage method outperforms two-stage methods by 5.56 mAP. Furthermore, we suggest an approach that partially answers "how many box-labelled annotations are necessary?" before training a machine learning model.

Urine Microscopic Image Dataset

Urinalysis is a standard diagnostic test to detect urinary system related problems. The automation of urinalysis will reduce the overall diagnostic time. Recent studies used urine microscopic datasets for designing deep learning based algorithms to classify and detect urine cells. But these datasets are not publicly available for further research. To alleviate the need for urine datsets, we prepare our urine sediment microscopic image (UMID) dataset comprising of around 3700 cell annotations and 3 categories of cells namely RBC, pus and epithelial cells. We discuss the several challenges involved in preparing the dataset and the annotations. We make the dataset publicly available.