From network analysis to experimental validation: identification of regulators of non-muscle myosin II contractility using the folded-gastrulation signaling pathway.

The morphogenetic process of apical constriction, which relies on non-muscle myosin II (NMII) generated constriction of apical domains of epithelial cells, is key to the development of complex cellular patterns. Apical constriction occurs in almost all multicellular organisms, but one of the most well-characterized systems is the Folded-gastrulation (Fog)-induced apical constriction that occurs in Drosophila. The binding of Fog to its cognizant receptors Mist/Smog results in a signaling cascade that leads to the activation of NMII-generated contractility. Despite our knowledge of key molecular players involved in Fog signaling, we sought to explore whether other proteins have an undiscovered role in its regulation. We developed a computational method to predict unidentified candidate NMII regulators using a network of pairwise protein-protein interactions called an interactome. We first constructed a Drosophila interactome of over 500,000 protein-protein interactions from several databases that curate high-throughput experiments. Next, we implemented several graph-based algorithms that predicted 14 proteins potentially involved in Fog signaling. To test these candidates, we used RNAi depletion in combination with a cellular contractility assay in Drosophila S2R + cells, which respond to Fog by contracting in a stereotypical manner. Of the candidates we screened using this assay, two proteins, the serine/threonine phosphatase Flapwing and the putative guanylate kinase CG11811 were demonstrated to inhibit cellular contractility when depleted, suggestive of their roles as novel regulators of the Fog pathway.

COVID-Net CXR-2: An Enhanced Deep Convolutional Neural Network Design for Detection of COVID-19 Cases From Chest X-ray Images.

As the COVID-19 pandemic devastates globally, the use of chest X-ray (CXR) imaging as a complimentary screening strategy to RT-PCR testing continues to grow given its routine clinical use for respiratory complaint. As part of the COVID-Net open source initiative, we introduce COVID-Net CXR-2, an enhanced deep convolutional neural network design for COVID-19 detection from CXR images built using a greater quantity and diversity of patients than the original COVID-Net. We also introduce a new benchmark dataset composed of 19,203 CXR images from a multinational cohort of 16,656 patients from at least 51 countries, making it the largest, most diverse COVID-19 CXR dataset in open access form. The COVID-Net CXR-2 network achieves sensitivity and positive predictive value of 95.5 and 97.0%, respectively, and was audited in a transparent and responsible manner. Explainability-driven performance validation was used during auditing to gain deeper insights in its decision-making behavior and to ensure clinically relevant factors are leveraged for improving trust in its usage. Radiologist validation was also conducted, where select cases were reviewed and reported on by two board-certified radiologists with over 10 and 19 years of experience, respectively, and showed that the critical factors leveraged by COVID-Net CXR-2 are consistent with radiologist interpretations.