State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
Published: November 2022
AI Article Synopsis
Article Abstract
The retrieval of hit/lead compounds with novel scaffolds during early drug development is an important but challenging task. Various generative models have been proposed to create drug-like molecules. However, the capacity of these generative models to design wet-lab-validated and target-specific molecules with novel scaffolds has hardly been verified. We herein propose a generative deep learning (GDL) model, a distribution-learning conditional recurrent neural network (cRNN), to generate tailor-made virtual compound libraries for given biological targets. The GDL model is then applied to RIPK1. Virtual screening against the generated tailor-made compound library and subsequent bioactivity evaluation lead to the discovery of a potent and selective RIPK1 inhibitor with a previously unreported scaffold, RI-962. This compound displays potent in vitro activity in protecting cells from necroptosis, and good in vivo efficacy in two inflammatory models. Collectively, the findings prove the capacity of our GDL model in generating hit/lead compounds with unreported scaffolds, highlighting a great potential of deep learning in drug discovery.
Background And Purpose: Segmentation imperfections (noise) in radiotherapy organ-at-risk segmentation naturally arise from specialist experience and image quality. Using clinical contours can result in sub-optimal convolutional neural network (CNN) training and performance, but manual curation is costly. We address the impact of simulated and clinical segmentation noise on CNN parotid gland (PG) segmentation performance and provide proof-of-concept for an easily implemented auto-curation countermeasure.
Deep learning models are used to minimize the number of polyps that goes unnoticed by the experts and to accurately segment the detected polyps during interventions. Although state-of-the-art models are proposed, it remains a challenge to define representations that are able to generalize well and that mediate between capturing low-level features and higher-level semantic details without being redundant. Another challenge with these models is that they are computation and memory intensive, which can pose a problem with real-time applications.
Breast cancer is one of the most common causes of death in women in the modern world. Cancerous tissue detection in histopathological images relies on complex features related to tissue structure and staining properties. Convolutional neural network (CNN) models like ResNet50, Inception-V1, and VGG-16, while useful in many applications, cannot capture the patterns of cell layers and staining properties.
Missing Alzheimer's disease (AD) data is prevalent and poses significant challenges for AD diagnosis. Previous studies have explored various data imputation approaches on AD data, but the systematic evaluation of deep learning algorithms for imputing heterogeneous and comprehensive AD data is limited. This study investigates the efficacy of denoising autoencoder-based imputation of missing key features of heterogeneous data that comprised tau-PET, MRI, cognitive and functional assessments, genotype, sociodemographic, and medical history.
Non-invasive brain-computer interfaces (BCI) hold great promise in the field of neurorehabilitation. They are easy to use and do not require surgery, particularly in the area of motor imagery electroencephalography (EEG). However, motor imagery EEG signals often have a low signal-to-noise ratio and limited spatial and temporal resolution.
