Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

Assessment of the Oral Bioavailability of Organic Contaminants in Humans

Bioavailability estimates the actual internal uptake or absorption of contaminants that enter the body (internal dose) and helps in providing a more accurate estimation of the human risks than the usage of total concentration. This is important for exposure assessment for children in relation to their hand-to-mouth activities. For example significant reductions of the bioavailability of long-term contaminated soils have been demonstrated using various animal models. The measurement for bioavailability involves various uncertainties for organic contaminants. It is crucial to determine the parameters that influence the results of bioavailability. This chapter provides a summary of the current state of knowledge for the determination of bioavailability for a range of organic contaminants. The information provided will be useful in facilitating further research efforts for the investigation of bioavailability of contaminants in conducting exposure assessments

One stop shop II: taxonomic update with molecular phylogeny for important phytopathogenic genera: 26–50 (2019)

This paper is the second in a series focused on providing a stable platform for the taxonomy of phytopathogenic fungi. It focuses on 25 phytopathogenic genera: Alternaria, Bipolaris, Boeremia, Botryosphaeria, Calonectria, Coniella, Corticiaceae, Curvularia, Elsinoe, Entyloma, Erythricium, Fomitiporia, Fulviformes, Laetisaria, Limonomyces, Neofabraea, Neofusicoccum, Phaeoacremonium, Phellinotus, Phyllosticta, Plenodomus, Pseudopyricularia, Tilletia, Venturia and Waitea, using recent molecular data, up to date names and the latest taxonomic insights. For each genus a taxonomic background, diversity aspects, species identification and classification based on molecular phylogeny and recommended genetic markers are provided. In this study, varieties of the genus Boeremia have been elevated to species level. Botryosphaeria, Bipolaris, Curvularia, Neofusicoccum and Phyllosticta that were included in the One Stop Shop 1 paper are provided with updated entries, as many new species have been introduced to these genera