scholarly journals CYPstrate: A Set of Machine Learning Models for the Accurate Classification of Cytochrome P450 Enzyme Substrates and Non-Substrates

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4678
Author(s):  
Malte Holmer ◽  
Christina de Bruyn Kops ◽  
Conrad Stork ◽  
Johannes Kirchmair
Keyword(s):  
Machine Learning ◽  
Cytochrome P450 ◽  
High Performance ◽  
Organic Molecules ◽  
Cytochrome P450 Enzyme ◽  
Learning Models ◽  
Cytochrome P450 Enzymes ◽  
Small Organic Molecules ◽  
Machine Learning Models

The interaction of small organic molecules such as drugs, agrochemicals, and cosmetics with cytochrome P450 enzymes (CYPs) can lead to substantial changes in the bioavailability of active substances and hence consequences with respect to pharmacological efficacy and toxicity. Therefore, efficient means of predicting the interactions of small organic molecules with CYPs are of high importance to a host of different industries. In this work, we present a new set of machine learning models for the classification of xenobiotics into substrates and non-substrates of nine human CYP isozymes: CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. The models are trained on an extended, high-quality collection of known substrates and non-substrates and have been subjected to thorough validation. Our results show that the models yield competitive performance and are favorable for the detection of CYP substrates. In particular, a new consensus model reached high performance, with Matthews correlation coefficients (MCCs) between 0.45 (CYP2C8) and 0.85 (CYP3A4), although at the cost of coverage. The best models presented in this work are accessible free of charge via the “CYPstrate” module of the New E-Resource for Drug Discovery (NERDD).

scholarly journals Predicting the Skin Sensitization Potential of Small Molecules with Machine Learning Models Trained on Biologically Meaningful Descriptors

2021 ◽  
Vol 14 (8) ◽  
pp. 790
Author(s):  
Anke Wilm ◽  
Marina Garcia de Lomana ◽  
Conrad Stork ◽  
Neann Mathai ◽  
Steffen Hirte ◽  
...  
Keyword(s):  
Machine Learning ◽  
Organic Molecules ◽  
Academic Research ◽  
Skin Sensitization ◽  
Learning Models ◽  
Data Set ◽  
Molecular Fingerprints ◽  
Small Organic Molecules ◽  
Significance Level ◽  
Machine Learning Models

In recent years, a number of machine learning models for the prediction of the skin sensitization potential of small organic molecules have been reported and become available. These models generally perform well within their applicability domains but, as a result of the use of molecular fingerprints and other non-intuitive descriptors, the interpretability of the existing models is limited. The aim of this work is to develop a strategy to replace the non-intuitive features by predicted outcomes of bioassays. We show that such replacement is indeed possible and that as few as ten interpretable, predicted bioactivities are sufficient to reach competitive performance. On a holdout data set of 257 compounds, the best model (“Skin Doctor CP:Bio”) obtained an efficiency of 0.82 and an MCC of 0.52 (at the significance level of 0.20). Skin Doctor CP:Bio is available free of charge for academic research. The modeling strategies explored in this work are easily transferable and could be adopted for the development of more interpretable machine learning models for the prediction of the bioactivity and toxicity of small organic compounds.

Analyzing Transaction Confirmation in Ethereum Using Machine Learning Techniques

2021 ◽  
Vol 48 (4) ◽  
pp. 12-15
Author(s):  
Vinicius C. Oliveira ◽  
Julia Almeida Valadares ◽  
Jose Eduardo A. Sousa ◽  
Alex Borges Vieira ◽  
Heder Soares Bernardino ◽  
...  
Keyword(s):  
Machine Learning ◽  
Roc Curve ◽  
High Performance ◽  
Machine Learning Techniques ◽  
Relevant Feature ◽  
Learning Models ◽  
Performance Models ◽  
Learning Techniques ◽  
Machine Learning Models

Ethereum has emerged as one of the most important cryptocurrencies in terms of the number of transactions. Given the recent growth of Ethereum, the cryptocurrency community and researchers are interested in understanding the Ethereum transactions behavior. In this work, we investigate a key aspect of Ethereum: the prediction of a transaction confirmation or failure based on its features. This is a challenging issue due to the small, but still relevant, fraction of failures in millions of recorded transactions and the complexity of the distributed mechanism to execute transactions in Ethereum. To conduct this investigation, we train machine learning models for this prediction, taking into consideration carefully balanced sets of confirmed and failed transactions. The results show high-performance models for classification of transactions with the best values of F1-score and area under the ROC curve approximately equal to 0.67 and 0.87, respectively. Also, we identified the gas used as the most relevant feature for the prediction.

scholarly journals Statistical and machine learning models for optimizing energy in parallel applications

2019 ◽  
Vol 33 (6) ◽  
pp. 1079-1097 ◽  
Author(s):  
Mark Endrei ◽  
Chao Jin ◽  
Minh Ngoc Dinh ◽  
David Abramson ◽  
Heidi Poxon ◽  
...  
Keyword(s):  
Machine Learning ◽  
Energy Efficiency ◽  
High Performance ◽  
Large Scale ◽  
Energy Use ◽  
Parallel Applications ◽  
Learning Models ◽  
Trade Off ◽  
Time Required ◽  
Machine Learning Models

Rising power costs and constraints are driving a growing focus on the energy efficiency of high performance computing systems. The unique characteristics of a particular system and workload and their effect on performance and energy efficiency are typically difficult for application users to assess and to control. Settings for optimum performance and energy efficiency can also diverge, so we need to identify trade-off options that guide a suitable balance between energy use and performance. We present statistical and machine learning models that only require a small number of runs to make accurate Pareto-optimal trade-off predictions using parameters that users can control. We study model training and validation using several parallel kernels and more complex workloads, including Algebraic Multigrid (AMG), Large-scale Atomic Molecular Massively Parallel Simulator, and Livermore Unstructured Lagrangian Explicit Shock Hydrodynamics. We demonstrate that we can train the models using as few as 12 runs, with prediction error of less than 10%. Our AMG results identify trade-off options that provide up to 45% improvement in energy efficiency for around 10% performance loss. We reduce the sample measurement time required for AMG by 90%, from 13 h to 74 min.

scholarly journals A Physics-Infused Deep Learning Model for the Prediction of Refractive Indices and Its Use for the Large-Scale Screening of Organic Compound Space

2019 ◽  
Author(s):  
Mojtaba Haghighatlari ◽  
Gaurav Vishwakarma ◽  
Mohammad Atif Faiz Afzal ◽  
Johannes Hachmann
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Large Scale ◽  
Organic Molecules ◽  
Learning Model ◽  
Training Data ◽  
Refractive Indices ◽  
Learning Models ◽  
Deep Learning Model ◽  
Machine Learning Models

<div><div><div><p>We present a multitask, physics-infused deep learning model to accurately and efficiently predict refractive indices (RIs) of organic molecules, and we apply it to a library of 1.5 million compounds. We show that it outperforms earlier machine learning models by a significant margin, and that incorporating known physics into data-derived models provides valuable guardrails. Using a transfer learning approach, we augment the model to reproduce results consistent with higher-level computational chemistry training data, but with a considerably reduced number of corresponding calculations. Prediction errors of machine learning models are typically smallest for commonly observed target property values, consistent with the distribution of the training data. However, since our goal is to identify candidates with unusually large RI values, we propose a strategy to boost the performance of our model in the remoter areas of the RI distribution: We bias the model with respect to the under-represented classes of molecules that have values in the high-RI regime. By adopting a metric popular in web search engines, we evaluate our effectiveness in ranking top candidates. We confirm that the models developed in this study can reliably predict the RIs of the top 1,000 compounds, and are thus able to capture their ranking. We believe that this is the first study to develop a data-derived model that ensures the reliability of RI predictions by model augmentation in the extrapolation region on such a large scale. These results underscore the tremendous potential of machine learning in facilitating molecular (hyper)screening approaches on a massive scale and in accelerating the discovery of new compounds and materials, such as organic molecules with high-RI for applications in opto-electronics.</p></div></div></div>

scholarly journals Multivariate Classification of Drugs using Parametric and Nonparametric Machine Learning Models

2020 ◽  
Vol 9 (3) ◽  
pp. 2021-2027
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Biological Activities ◽  
Biological Effects ◽  
Recursive Feature Elimination ◽  
Drug Candidate ◽  
Learning Models ◽  
Machine Learning Models ◽  
Non Parametric

In pharmaceutical research, traditional drug discovery process is time consuming and expensive, where several compounds are experimentally tested for their biological activities. Series of lab experiments are conducted to analyze newly synthesized drug’s pharmaceutical activities and its biological effects on human. With every new drug discovery, the required clinical properties can be determined using machine learning models and this greatly reduces the experimental cost. This paper explores parametric and non-parametric machine learning models to classify administration properties of drugs and its toxicity. The multinomial classification of drugs was based on their physicochemical and ADMET properties. Balanced data samples were drawn from chEMBL and was pre-processed. Features were reduced using Recursive Feature Elimination and the attributes were ranked based on their importance to reduce highly correlated attributes. The performance of parametric and non-parametric machine learning models was analyzed on cheminformatic data that includes physiochemical, biological and pharmaceutical properties of the drug molecules. Selecting the potent drug candidate along with its administration properties greatly reduces wet lab experimental time and cost. Multiclass classification can be determined efficiently using non-parametric machine learning model. Optimal feature engineering, tuning hyperparameters and adopting hybrid algorithms would result in more accurate predictions in future for cheminformatics data.

The Classification of Skateboarding Tricks by Means of the Integration of Transfer Learning and Machine Learning Models

2020 ◽  
pp. 219-226
Author(s):  
Muhammad Nur Aiman Shapiee ◽  
Muhammad Ar Rahim Ibrahim ◽  
Mohd Azraai Mohd Razman ◽  
Muhammad Amirul Abdullah ◽  
Rabiu Muazu Musa ◽  
...  
Keyword(s):  
Machine Learning ◽  
Transfer Learning ◽  
Learning Models ◽  
Machine Learning Models
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