Combination therapies are commonly used to treat patients with complex diseases that respond poorly to single-agent therapies. high-throughput drug screening is a standard method for preclinical prioritization of synergistic drug combinations, but it can be impractical for large drug sets. Computational methods are thus being actively explored; however, most published methods were built on a limited size of cancer cell lines or drugs, and it remains a challenge to predict synergism at a large scale where the diversity within the data escalates the difficulty of prediction. Here, we present a state-of-the-field synergy prediction algorithm, which ranked first in all subchallenges in the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge. The model was built and evaluated using the largest drug combination screening dataset at the time of the competition, consisting of approximately 11,500 experimentally tested synergy scores of 118 drugs in 85 cancer cell lines. We developed a novel feature extraction strategy by integrating the cross-cell and cross-drug information with a novel network propagation method and then assembled the information in monotherapy and simulated molecular data to predict drug synergy. This represents a significant conceptual advancement of synergy prediction, using extracted features in the form of simulated posttreatment molecular profiles when only the pretreatment molecular profile is available. Our cross-tissue synergism prediction algorithm achieves promising accuracy comparable with the correlation between experimental replicates and can be applied to other cancer cell lines and drugs to guide therapeutic choices. This study presents a novel network propagation-based method that predicts anticancer drug synergy to the accuracy of experimental replicates, which establishes a state-of-the-field method as benchmarked by the pharmacogenomics research community involving models generated by 160 teams. .

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Purpose To develop a method for predicting postoperative anterior chamber depth (ACD) in cataract surgery patients based on preoperative biometry, demographics, and intraocular lens (IOL) power. Methods Patients who underwent cataract surgery and had both preoperative and postoperative biometry measurements were included. Patient demographics and IOL power were collected from the Sight Outcomes Research Collaborative (SOURCE) database. A gradient-boosting decision tree model was developed to predict the postoperative ACD. The mean absolute error (MAE) and median absolute error (MedAE) were used as evaluation metrics. The performance of the proposed method was compared with five existing formulas. Results In total, 847 patients were assigned randomly in a 4:1 ratio to a training/validation set (678 patients) and a testing set (169 patients). Using preoperative biometry and patient sex as predictors, the presented method achieved an MAE of 0.106 ± 0.098 (SD) on the testing set, and a MedAE of 0.082. MAE was significantly lower than that of the five existing methods ( P < 0.01). When keratometry was excluded, our method attained an MAE of 0.123 ± 0.109, and a MedAE of 0.093. When IOL power was used as an additional predictor, our method achieved an MAE of 0.105 ± 0.091 and a MedAE of 0.080. Conclusions The presented machine learning method achieved greater accuracy than previously reported methods for the prediction of postoperative ACD. Translational Relevance Increasing accuracy of postoperative ACD prediction with the presented algorithm has the potential to improve refractive outcomes in cataract surgery.

AimsTo assess whether incorporating a machine learning (ML) method for accurate prediction of postoperative anterior chamber depth (ACD) improves the refraction prediction performance of existing intraocular lens (IOL) calculation formulas.MethodsA dataset of 4806 patients with cataract was gathered at the Kellogg Eye Center, University of Michigan, and split into a training set (80% of patients, 5761 eyes) and a testing set (20% of patients, 961 eyes). A previously developed ML-based method was used to predict the postoperative ACD based on preoperative biometry. This ML-based postoperative ACD was integrated into new effective lens position (ELP) predictions using regression models to rescale the ML output for each of four existing formulas (Haigis, Hoffer Q, Holladay and SRK/T). The performance of the formulas with ML-modified ELP was compared using a testing dataset. Performance was measured by the mean absolute error (MAE) in refraction prediction.ResultsWhen the ELP was replaced with a linear combination of the original ELP and the ML-predicted ELP, the MAEs±SD (in Diopters) in the testing set were: 0.356±0.329 for Haigis, 0.352±0.319 for Hoffer Q, 0.371±0.336 for Holladay, and 0.361±0.331 for SRK/T which were significantly lower (p<0.05) than those of the original formulas: 0.373±0.328 for Haigis, 0.408±0.337 for Hoffer Q, 0.384±0.341 for Holladay and 0.394±0.351 for SRK/T.ConclusionUsing a more accurately predicted postoperative ACD significantly improves the prediction accuracy of four existing IOL power formulas.