AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Noncardiac Chest Pain and Psychopathology in Children and Adolescents

Objective: We sought to examine the prevalence of DSM-IV psychiatric disorders in children and adolescents with complaints of noncardiac chest pain (NCCP). Method: We assessed 27 youngsters (ages 8-17 years) referred to a pediatric cardiology practice with complaints of NCCP. Each child and a parent were interviewed using the Anxiety Disorders Interview Schedule for Children. Results: Sixteen youngsters (59%) were diagnosed with a current DSM-IV disorder. Fifteen (56%) had a current anxiety disorder, nine of whom were diagnosed with panic disorder. One participant was diagnosed with a depressive disorder. Conclusion: Results of this preliminary study suggest that DSM-IV anxiety disorders may be common in youngsters with NCCP. No evidence was found for high prevalence of depression in this sample. Larger controlled studies are needed to determine the prevalence and impact of psychopathology in youngsters with NCCP

Anxiety and Depressive Symptoms and Anxiety Sensitivity in Youngsters with Noncardiac Chest Pain and Benign Heart Murmurs

Objective: Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. Methods: We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. Results: Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. Conclusions: Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations