Comparing Machine Learning Models for Aromatase (P450 19A1).
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ABSTRACT:
SUBMITTER: Zorn KM
PROVIDER: S-EPMC8194505 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tuberculosis is a global health dilemma. In 2016, the WHO reported 10.4 million incidences and 1.7 million deaths. The need to develop new treatments for those infected with Mycobacterium tuberculosis ( Mtb) has led to many large-scale phenotypic screens and many thousands of new active compounds identified in vitro. However, with limited funding, efforts to discover new active molecules against Mtb needs to be more efficient. Several computational machine learning approaches have been shown to have good enrichment and hit rates. We have curated small molecule Mtb data and developed new models with a total of 18,886 molecules with activity cutoffs of 10 μM, 1 μM, and 100 nM. These data sets were used to evaluate different machine learning methods (including deep learning) and metrics and to generate predictions for additional molecules published in 2017. One Mtb model, a combined in vitro and in vivo data Bayesian model at a 100 nM activity yielded the following metrics for 5-fold cross validation: accuracy = 0.88, precision = 0.22, recall = 0.91, specificity = 0.88, kappa = 0.31, and MCC = 0.41. We have also curated an evaluation set ( n = 153 compounds) published in 2017, and when used to test our model, it showed the comparable statistics (accuracy = 0.83, precision = 0.27, recall = 1.00, specificity = 0.81, kappa = 0.36, and MCC = 0.47). We have also compared these models with additional machine learning algorithms showing Bayesian machine learning models constructed with literature Mtb data generated by different laboratories generally were equivalent to or outperformed deep neural networks with external test sets. Finally, we have also compared our training and test sets to show they were suitably diverse and different in order to represent useful evaluation sets. Such Mtb machine learning models could help prioritize compounds for testing in vitro and in vivo.
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Project description:In recent decades, the global incidence of dengue has increased. Affected countries have responded with more effective surveillance strategies to detect outbreaks early, monitor the trends, and implement prevention and control measures. We have applied newly developed machine learning approaches to identify laboratory-confirmed dengue cases from 4,894 emergency department patients with dengue-like illness (DLI) who received laboratory tests. Among them, 60.11% (2942 cases) were confirmed to have dengue. Using just four input variables [age, body temperature, white blood cells counts (WBCs) and platelets], not only the state-of-the-art deep neural network (DNN) prediction models but also the conventional decision tree (DT) and logistic regression (LR) models delivered performances with receiver operating characteristic (ROC) curves areas under curves (AUCs) of the ranging from 83.75% to 85.87% [for DT, DNN and LR: 84.60% ± 0.03%, 85.87% ± 0.54%, 83.75% ± 0.17%, respectively]. Subgroup analyses found all the models were very sensitive particularly in the pre-epidemic period. Pre-peak sensitivities (<35 weeks) were 92.6%, 92.9%, and 93.1% in DT, DNN, and LR respectively. Adjusted odds ratios examined with LR for low WBCs [? 3.2 (x103/?L)], fever (?38°C), low platelet counts [< 100 (x103/?L)], and elderly (? 65 years) were 5.17 [95% confidence interval (CI): 3.96-6.76], 3.17 [95%CI: 2.74-3.66], 3.10 [95%CI: 2.44-3.94], and 1.77 [95%CI: 1.50-2.10], respectively. Our prediction models can readily be used in resource-poor countries where viral/serologic tests are inconvenient and can also be applied for real-time syndromic surveillance to monitor trends of dengue cases and even be integrated with mosquito/environment surveillance for early warning and immediate prevention/control measures. In other words, a local community hospital/clinic with an instrument of complete blood counts (including platelets) can provide a sentinel screening during outbreaks. In conclusion, the machine learning approach can facilitate medical and public health efforts to minimize the health threat of dengue epidemics. However, laboratory confirmation remains the primary goal of surveillance and outbreak investigation.
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Project description:BACKGROUND AND PURPOSE:MR imaging-based modeling of tumor cell density can substantially improve targeted treatment of glioblastoma. Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a transfer learning method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient's own histologic data. MATERIALS AND METHODS:We recruited patients with primary glioblastoma undergoing image-guided biopsies and preoperative imaging, including contrast-enhanced MR imaging, dynamic susceptibility contrast MR imaging, and diffusion tensor imaging. We calculated relative cerebral blood volume from DSC-MR imaging and mean diffusivity and fractional anisotropy from DTI. Following image coregistration, we assessed tumor cell density for each biopsy and identified corresponding localized MR imaging measurements. We then explored a range of univariate and multivariate predictive models of tumor cell density based on MR imaging measurements in a generalized one-model-fits-all approach. We then implemented both univariate and multivariate individualized transfer learning predictive models, which harness the available population-level data but allow individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized transfer learning and generalized one-model-fits-all models. RESULTS:Tumor cell density significantly correlated with relative CBV (r = 0.33, P < .001), and T1-weighted postcontrast (r = 0.36, P < .001) on univariate analysis after correcting for multiple comparisons. With single-variable modeling (using relative CBV), transfer learning increased predictive performance (r = 0.53, mean absolute error = 15.19%) compared with one-model-fits-all (r = 0.27, mean absolute error = 17.79%). With multivariate modeling, transfer learning further improved performance (r = 0.88, mean absolute error = 5.66%) compared with one-model-fits-all (r = 0.39, mean absolute error = 16.55%). CONCLUSIONS:Transfer learning significantly improves predictive modeling performance for quantifying tumor cell density in glioblastoma.
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Project description:(1) Medical research has shown an increasing interest in machine learning, permitting massive multivariate data analysis. Thus, we developed drug intoxication mortality prediction models, and compared machine learning models and traditional logistic regression. (2) Categorized as drug intoxication, 8,937 samples were extracted from the Korea Centers for Disease Control and Prevention (2008-2017). We trained, validated, and tested each model through data and compared their performance using three measures: Brier score, calibration slope, and calibration-in-the-large. (3) A chi-square test demonstrated that mortality risk statistically significantly differed according to severity, intent, toxic substance, age, and sex. The multilayer perceptron model (MLP) had the highest area under the curve (AUC), and lowest Brier score in training and validation phases, while the logistic regression model (LR) showed the highest AUC (0.827) and lowest Brier score (0.0307) in the testing phase. MLP also had the second-highest AUC (0.816) and second-lowest Brier score (0.003258) in the testing phase, demonstrating better performance than the decision-making tree model. (4) Given the complexity of choosing tuning parameters, LR proved competitive when using medical datasets, which require strict accuracy.
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Project description:Quantum computing and artificial intelligence, combined together, may revolutionize future technologies. A significant school of thought regarding artificial intelligence is based on generative models. Here, we propose a general quantum algorithm for machine learning based on a quantum generative model. We prove that our proposed model is more capable of representing probability distributions compared with classical generative models and has exponential speedup in learning and inference at least for some instances if a quantum computer cannot be efficiently simulated classically. Our result opens a new direction for quantum machine learning and offers a remarkable example where a quantum algorithm shows exponential improvement over classical algorithms in an important application field.
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Project description:BACKGROUND:Diabetes Mellitus is an increasingly prevalent chronic disease characterized by the body's inability to metabolize glucose. The objective of this study was to build an effective predictive model with high sensitivity and selectivity to better identify Canadian patients at risk of having Diabetes Mellitus based on patient demographic data and the laboratory results during their visits to medical facilities. METHODS:Using the most recent records of 13,309 Canadian patients aged between 18 and 90 years, along with their laboratory information (age, sex, fasting blood glucose, body mass index, high-density lipoprotein, triglycerides, blood pressure, and low-density lipoprotein), we built predictive models using Logistic Regression and Gradient Boosting Machine (GBM) techniques. The area under the receiver operating characteristic curve (AROC) was used to evaluate the discriminatory capability of these models. We used the adjusted threshold method and the class weight method to improve sensitivity - the proportion of Diabetes Mellitus patients correctly predicted by the model. We also compared these models to other learning machine techniques such as Decision Tree and Random Forest. RESULTS:The AROC for the proposed GBM model is 84.7% with a sensitivity of 71.6% and the AROC for the proposed Logistic Regression model is 84.0% with a sensitivity of 73.4%. The GBM and Logistic Regression models perform better than the Random Forest and Decision Tree models. CONCLUSIONS:The ability of our model to predict patients with Diabetes using some commonly used lab results is high with satisfactory sensitivity. These models can be built into an online computer program to help physicians in predicting patients with future occurrence of diabetes and providing necessary preventive interventions. The model is developed and validated on the Canadian population which is more specific and powerful to apply on Canadian patients than existing models developed from US or other populations. Fasting blood glucose, body mass index, high-density lipoprotein, and triglycerides were the most important predictors in these models.
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Project description:Recently, the use of machine-learning (ML) models for pharmacokinetic (PK) modeling has grown significantly. Although most of the current approaches use ML techniques as black boxes, there are only a few that have proposed interpretable architectures which integrate mechanistic knowledge. In this work, we use as the test case a one-compartment PK model using a scientific machine learning (SciML) framework and consider learning an unknown absorption using neural networks, while simultaneously estimating other parameters of drug distribution and elimination. We generate simulated data with different sampling strategies to show that our model can accurately predict concentrations in extrapolation tasks, including new dosing regimens with different sparsity levels, and produce reliable forecasts even for new patients. By using a scenario of fitting PK data with complex absorption, we demonstrate that including known physiological structure into an SciML model allows us to obtain highly accurate predictions while preserving the interpretability of classical compartmental models.
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