64 research outputs found
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
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Primary lung carcinoma metastatic to a solitary fibrous tumor.
We report the case of a 78-year-old man with a 2 month history of newly diagnosed metastatic lung adenocarcinoma, who presented with a left gluteal soft tissue mass. Histological examination of the mass revealed a solitary fibrous tumor containing metastases from adenocarcinoma
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Acknowledging crossing-avoidance heuristic violations when solving the Euclidean travelling salesperson problem
If a salesperson aims to visit a number of cities only once before returning home, which route should they take to minimise the total distance/cost? This combinatorial optimization problem is called the travelling salesperson problem (TSP) and has a rapid growth in the number of possible solutions as the number of cities increases. Despite its complexity, when cities and routes are represented in 2D Euclidean space (ETSP), humans solve the problem with relative ease, by applying simple visual heuristics.
One of the most important heuristics appears to be the avoidance of path crossings, which will always result in more optimal solutions than tours that contain crossings.
This study systematically investigates whether the occurrence of crossings is impacted by geometric properties by modelling their relationship using binomial logistic regression as well as random forests. Results show that properties, such as the number of nodes making up the convex hull, the standard deviation of the angles between nodes, the average distance between all nodes in the graph, the total number of nodes in the graph, and the tour cost (i.e., a measure of performance), are significant predictors of whether crossings are likely to occur
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