Machine learning small molecule properties in drug discovery

Machine learning methods have been applied to many data sets in pharmaceutical research for several decades. The relative ease and availability of fingerprint type molecular descriptors paired with Bayesian methods resulted in the widespread use of this approach for a diverse array of end points relevant to drug discovery. Deep learning is the latest machine learning algorithm attracting attention for many of pharmaceutical applications from docking to virtual screening. Deep learning is based on an artificial neural network with multiple hidden layers and has found considerable traction for many artificial intelligence applications. We have previously suggested the need for a comparison of different machine learning methods with deep learning across an array of varying data sets that is applicable to pharmaceutical research. End points relevant to pharmaceutical research include absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, as well as activity against pathogens and drug discovery data sets. In this study, we have used data sets for solubility, probe-likeness, hERG, KCNQ1, bubonic plague, Chagas, tuberculosis, and malaria to compare different machine learning methods using FCFP6 fingerprints. These data sets represent whole cell screens, individual proteins, physicochemical properties as well as a data set with a complex end point. Our aim was to assess whether deep learning offered any improvement in testing when assessed using an array of metrics including AUC, F1 score, Cohen's kappa, Matthews correlation coefficient and others. Based on ranked normalized scores for the metrics or data sets Deep Neural Networks (DNN) ranked higher than SVM, which in turn was ranked higher than all the other machine learning methods. Visualizing these properties for training and test sets using radar type plots indicates when models are inferior or perhaps over trained. These results also suggest the need for assessing deep learning further using multiple metrics with much larger scale comparisons, prospective testing as well as assessment of different fingerprints and DNN architectures beyond those used.

Machine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. In a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. PubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. In total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. Statistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. PROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250.

SummaryAccurate prediction of the solubility of chemical substances in solvents remains a challenge. The sparsity of high-quality solubility data is recognized as the biggest hurdle in the development of robust data-driven methods for practical use. Nonetheless, the effects of the quality and quantity of data on aqueous solubility predictions have not yet been scrutinized. In this study, the roles of the size and the quality of data sets on the performances of the solubility prediction models are unraveled, and the concepts of actual and observed performances are introduced. In an effort to curtail the gap between actual and observed performances, a quality-oriented data selection method, which evaluates the quality of data and extracts the most accurate part of it through statistical validation, is designed. Applying this method on the largest publicly available solubility database and using a consensus machine learning approach, a top-performing solubility prediction model is achieved.

Small data, big challenges: Machine- and deep-learning strategies for data-limited drug discovery.

Artificial intelligence has been applied in wildfire science and management since the 1990s, with early applications including neural networks and expert systems. Since then, the field has rapidly progressed congruently with the wide adoption of machine learning (ML) methods in the environmental sciences. Here, we present a scoping review of ML applications in wildfire science and management. Our overall objective is to improve awareness of ML methods among wildfire researchers and managers, as well as illustrate the diverse and challenging range of problems in wildfire science available to ML data scientists. To that end, we first present an overview of popular ML approaches used in wildfire science to date and then review the use of ML in wildfire science as broadly categorized into six problem domains, including (i) fuels characterization, fire detection, and mapping; (ii) fire weather and climate change; (iii) fire occurrence, susceptibility, and risk; (iv) fire behavior prediction; (v) fire effects; and (vi) fire management. Furthermore, we discuss the advantages and limitations of various ML approaches relating to data size, computational requirements, generalizability, and interpretability, as well as identify opportunities for future advances in the science and management of wildfires within a data science context. In total, to the end of 2019, we identified 300 relevant publications in which the most frequently used ML methods across problem domains included random forests, MaxEnt, artificial neural networks, decision trees, support vector machines, and genetic algorithms. As such, there exists opportunities to apply more current ML methods — including deep learning and agent-based learning — in the wildfire sciences, especially in instances involving very large multivariate datasets. We must recognize, however, that despite the ability of ML models to learn on their own, expertise in wildfire science is necessary to ensure realistic modelling of fire processes across multiple scales, while the complexity of some ML methods such as deep learning requires a dedicated and sophisticated knowledge of their application. Finally, we stress that the wildfire research and management communities play an active role in providing relevant, high-quality, and freely available wildfire data for use by practitioners of ML methods.

This dissertation addresses two significant issues in the effective application of machine learning algorithms and models for the physical and engineering sciences. The first is the broad challenge of automated modeling of data across different processes in a physical system. The second is the dilemma of obtaining insightful interpretations on the relationships between the inputs and outcome of a system as inferred from complex, black box machine learning models.Automated Geometric Shape Deviation Modeling for Additive Manufacturing SystemsAdditive manufacturing systems possess an intrinsic capability for one-of-a-kind manufacturing of a vast variety of shapes across a wide spectrum of processes. One major issue in AM systems is geometric accuracy control for the inevitable shape deviations that arise in AM processes. Current effective approaches for shape deviation control in AM involve the specification of statistical or machine learning deviation models for additively manufactured products. However, this task is challenging due to the constraints on the number of test shapes that can be manufactured in practice, and limitations on user efforts that can be devoted for learning deviation models across different shape classes and processes in an AM system. We develop an automated, Bayesian neural network methodology for comprehensive shape deviation modeling in an AM system. A fundamental innovation in this machine learning method is our new and connectable neural network structures that facilitate the transfer of prior knowledge and models on deviations across different shape classes and AM processes. Several case studies on in-plane and out-of-plane deviations, regular and free-form shapes, and different settings of lurking variables serve to validate the power and broad scope of our methodology, and its potential to advance high-quality manufacturing in an AM system.Interpretable Machine LearningMachine learning algorithms and models constitute the dominant set of predictive methods for a wide range of complex, real-world processes. However, interpreting what such methods effectively infer from data is difficult in general. This is because their typical black box natures possess a limited ability to directly yield insights on the underlying relationships between inputs and the outcome for a process. We develop methodologies based on new predictive comparison estimands that effectively enable one to ``mine’’ machine learning models, in the sense of (a) interpreting their inferred associations between inputs and/or functional forms of inputs with the outcome, (b) identifying the inputs that they effectively consider relevant, and (c) interpreting the inferred conditional and two-way associations of the inputs with the outcome. We establish Fisher consistent estimators, and their corresponding standard errors, for our new estimands under a condition on the inputs' distributions. The significance of our predictive comparison methodology is demonstrated with a wide range of simulation and case studies that involve Bayesian additive regression trees, neural networks, and support vector machines. Our extended study of interpretable machine learning for AM systems demonstrates how our method can contribute to smarter advanced manufacturing systems, especially as current machine learning methods for AM are lacking in their ability to yield meaningful engineering knowledge on AM processes.

Shear viscosity, though being a fundamental property of all fluids, is computationally expensive to calculate from equilibrium molecular dynamics simulations. Recently, machine learning (ML) methods have been used to augment molecular simulations in many contexts, thus showing promise to estimate viscosity too in a relatively inexpensive manner. However, ML methods face significant challenges—such as overfitting, when the size of the data set is small, as is the case with viscosity. In this work, we train seven ML models to predict the shear viscosity of a Lennard–Jones fluid, with particular emphasis on addressing issues arising from a small data set. Specifically, the issues related to model selection, performance estimation and uncertainty quantification were investigated. First, we show that the widely used performance estimation procedure of using a single unseen data set shows a wide variability—in estimating the errors on—small data sets. In this context, the common practice of using cross validation (CV) to select the hyperparameters (model selection) can be adapted to estimate the generalization error (performance estimation) as well. We compare two simple CV procedures for their ability to do both model selection and performance estimation, and find that k-fold CV based procedure shows a lower variance of error estimates. Also, these CV procedures naturally lead to an ensemble of trained ML models. We discuss the role of performance metrics in training and evaluation and propose a method to rank the ML models based on multiple metrics. Finally, two methods for uncertainty quantification—Gaussian process regression (GPR) and ensemble method—were used to estimate the uncertainty on individual predictions. The uncertainty estimates from GPR were also used to construct an applicability domain using which the ML models provided even more reliable predictions on an independent viscosity data set generated in this work. Overall, the procedures prescribed in this work, together, lead to robust ML models for small data sets.

Learning What Makes Catalysts Good

P125. Development of a novel ensemble machine learning algorithm for prediction of complications and readmission after anterior cervical spinal fusion

PD27-01 DEVELOPMENT OF A MACHINE LEARNING (ML) MODEL TO AUTOMATICALLY AND PRECISELY IDENTIFY KIDNEY STONES FROM URETEROSCOPY VIDEO RECORDINGS

Typhoon‐induced storm surges have been the most destructive disasters in coastal regions. The nowcasting of storm surge, in which the prediction lead time is not greater than 3 hr, is critical to disaster emergency response and recovery, enabling governments to make decisions and take actions according to the latest situation and prediction. Machine learning (ML) methods have been increasingly applied to storm surge predictions, but few ML studies focused on short‐term nowcasts. Moreover, conflicting conclusions often arise regarding the superiority of ML methods and model input variables for storm surge predictions. This study highlights the significance of surge autocorrelation, that is, the correlation of surge height with its local historical values, in the design of ML models for storm surge nowcasts. It is shown in the comparative analyses of model input variables that, independent of the adopted ML methods, models relying solely on historical surge heights as inputs are sufficient to achieve reasonably accurate nowcasts of surge height. Conversely, models without historical surge heights in their inputs yield comparable prediction errors. Involving surge autocorrelation, simple multilayer perceptron models perform even better than sequential‐compatible recurrent neural network category of models. Moreover, it is illustrated that the surge autocorrelation inhibits the performance of Transformer and XGBoost models for storm surge nowcasts. This study shows the possibility to achieve efficient and accurate nowcasts (a lead time under 3 hr) of localized storm surge only based on limited observations by local tide gauge, supporting decision‐making in disaster emergency response and recovery within small‐scale coastal regions.

Chemical heuristics have been fundamental to the advancement of chemistry and materials science. These heuristics are typically established by scientists using knowledge and creativity to extract patterns from limited datasets. Machine learning offers opportunities to perfect this approach using computers and larger datasets. Here, we discuss the relationships between traditional heuristics and machine learning approaches. We show how traditional rules can be challenged by large-scale statistical assessment and how traditional concepts commonly used as features are feeding the machine learning techniques. We stress the waste involved in relearning chemical rules and the challenges in terms of data size requirements for purely data-driven approaches. Our view is that heuristic and machine learning approaches are at their best when they work together.

Real-time porosity prediction using gas-while-drilling data and machine learning with reservoir associated gas: Case study for Hassi Messaoud field, Algeria

During hydraulic fracturing jobs, engineers must monitor the wellhead pressure and adjust the pumping schedule in real time to avoid screenout, optimize the proppant and fluid amounts, and minimize cost. In this paper, we use machine learning to predict wellhead pressure in real time during hydraulic fracturing. The new algorithm can assist engineers in monitoring and optimizing the pumping schedule. We explored several neural network models. For each hydraulic fracturing stage, we train a machine learning (ML) model with the data from the first several minutes and predict the wellhead pressure for the next several minutes; we then add the data for the next several minutes, train a second ML model and predict the pressure for the next couple of minutes; and so on. We used several performance metrics to compare different models and select the best model for deployment to the Cloud, where a real-time completions platform is developed and hosted. We selected more than 100 hydraulic fracturing stages from several wells completed in the Delaware Basin and tested several ML methods on the historical data. The wellhead pressure can be predicted with an acceptable accuracy by a slightly nonlinear machine learning model. We tested the ML model on the Cloud, where real-time streaming data such as slurry rate and proppant concentration are gathered. The computation is fast enough that a real-time wellhead pressure can be predicted.

Coastal aquifers are vital for sustaining ecosystems and providing freshwater for agriculture and domestic use. However, rising groundwater salinity in these regions demands innovative approaches for accurate modeling and prediction. In recent decades, machine learning (ML) and deep learning (DL) techniques have been extensively used across various water resource management fields, often yielding promising outcomes. This review examines the growing usage of ML and DL techniques in modeling groundwater salinity in coastal aquifers. The analysis is based on 104 peer-reviewed journal articles including the review articles indexed in PubMed, ScienceDirect, Google Scholar, Scopus, and SpringerLink using keywords like "saltwater intrusion", "machine learning", “deep learning”, and "groundwater salinity". The review discusses recent advancements, challenges, and future directions for improving ML model accuracy and applicability. Studies reveal an increasing reliance on ML techniques to predict groundwater salinity and manage seawater intrusion across various coastal geological settings. Researchers have employed a range of ML models, from traditional methods like Artificial Neural Networks and Adaptive Neuro Fuzzy Inference Systems to advanced DL-based models like Convolutional Neural Networks and Long Short-Term Memory Networks, often using ensemble methods to enhance accuracy. Key findings include the top-tier output of ensemble and optimized models, including Random Forest and Grasshopper Optimization Algorithm-XGBoost. These studies highlight the importance of model selection, input variable ranking, and computational efficiency, demonstrating ML's global relevance in environmental management. The review highlights the prospects of ML, DL, and ensemble models to redefine groundwater management in coastal aquifers, offering more effective and sustainable solutions to the challenges posed by groundwater salinity and saltwater intrusion. Future advancements will focus on further integrating DL, explainable artificial intelligence, and ensemble approaches, along with other innovative techniques, to explore sparsely studied variables, model new or unique study areas, and apply ML methods for managing groundwater salinity.