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

Determinants of Second-Order Bile Duct Visualization at CT Cholangiography in Potential Living Liver Donors

View looking up the northwest corner; The Marriott Château Champlain is a hotel in Montreal, Quebec overlooking Dorchester Square. Once owned by CP Hotels and later sold off in the 1990s, it is now part of the Marriott hotel chain. Finished in time for the 1967 world's fair with its famous round porthole-like windows, Marriott Château Champlain stands 133 m (436 ft) high with 38 floors. It was built as the tallest hotel in Montreal and still holds that title to this date. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 2/8/2008

Determinants of Second-Order Bile Duct Visualization at CT Cholangiography in Potential Living Liver Donors

OBJECTIVE: The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors. MATERIALS AND METHODS: We retrospectively identified 143 potential living liver donors (83 men and 60 women; mean age, 37 years) evaluated with CT cholangiography, which included a slow infusion of iodipamide meglumine with CT acquisition 15 minutes after biliary contrast agent administration. Two readers independently scored the visualization of the second-order bile duct branches on a previously established 4-point scale (0 = not seen, 1 = faintly seen, 2 = well seen, and 3 = excellent visualization). Multivariate analysis was used to investigate the correlation between visualization scores and potential determinants of second-order bile duct opacification, specifically age, body mass index, creatinine level, total and direct bilirubin levels, alkaline phosphatase level, aspartate aminotransferase level, alanine aminotransferase level, patient maximum linear width, CT noise, and hepatosplenic attenuation difference at unenhanced CT. RESULTS: The mean (± SD) second-order bile duct visualization scores were 2.35 ± 0.66 and 2.55 ± 0.60 for readers 1 and 2, respectively. In the multivariate analysis, the only independent predictors of reduced second-order bile duct visualization were higher alkaline phosphatase level (p = 0.01) and higher CT noise (p = 0.02). CONCLUSION: Higher serum alkaline phosphatase level and higher CT noise in potential living liver donors indicate a higher risk of poor second-order bile duct visualization at CT cholangiography