Epigenetic Target Prediction with Accurate Machine Learning Models

2021 ◽  
Author(s):  
Norberto Sánchez-Cruz ◽  
Jose L. Medina-Franco
Keyword(s):  
Machine Learning ◽  
Small Molecules ◽  
Predictive Models ◽  
Large Scale ◽  
Target Prediction ◽  
Quantitative Measure ◽  
Learning Models ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Machine Learning Models

<p>Epigenetic targets are a significant focus for drug discovery research, as demonstrated by the eight approved epigenetic drugs for treatment of cancer and the increasing availability of chemogenomic data related to epigenetics. This data represents a large amount of structure-activity relationships that has not been exploited thus far for the development of predictive models to support medicinal chemistry efforts. Herein, we report the first large-scale study of 26318 compounds with a quantitative measure of biological activity for 55 protein targets with epigenetic activity. Through a systematic comparison of machine learning models trained on molecular fingerprints of different design, we built predictive models with high accuracy for the epigenetic target profiling of small molecules. The models were thoroughly validated showing mean precisions up to 0.952 for the epigenetic target prediction task. Our results indicate that the herein reported models have considerable potential to identify small molecules with epigenetic activity. Therefore, our results were implemented as freely accessible and easy-to-use web application.</p>

Epigenetic Target Prediction with Accurate Machine Learning Models

2021 ◽  
Author(s):  
Norberto Sánchez-Cruz ◽  
Jose L. Medina-Franco
Keyword(s):  
Machine Learning ◽  
Small Molecules ◽  
Predictive Models ◽  
Large Scale ◽  
Target Prediction ◽  
Quantitative Measure ◽  
Learning Models ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Machine Learning Models

<p>Epigenetic targets are a significant focus for drug discovery research, as demonstrated by the eight approved epigenetic drugs for treatment of cancer and the increasing availability of chemogenomic data related to epigenetics. This data represents a large amount of structure-activity relationships that has not been exploited thus far for the development of predictive models to support medicinal chemistry efforts. Herein, we report the first large-scale study of 26318 compounds with a quantitative measure of biological activity for 55 protein targets with epigenetic activity. Through a systematic comparison of machine learning models trained on molecular fingerprints of different design, we built predictive models with high accuracy for the epigenetic target profiling of small molecules. The models were thoroughly validated showing mean precisions up to 0.952 for the epigenetic target prediction task. Our results indicate that the herein reported models have considerable potential to identify small molecules with epigenetic activity. Therefore, our results were implemented as freely accessible and easy-to-use web application.</p>

scholarly journals Kipoi: accelerating the community exchange and reuse of predictive models for genomics

2018 ◽  
Author(s):  
Žiga Avsec ◽  
Roman Kreuzhuber ◽  
Johnny Israeli ◽  
Nancy Xu ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Machine Learning ◽  
Predictive Models ◽  
Genetic Variants ◽  
Large Scale ◽  
Learning Models ◽  
Unified Framework ◽  
Transcriptional Gene Regulation ◽  
Automated Software ◽  
Variant Effect Prediction ◽  
Machine Learning Models

AbstractAdvanced machine learning models applied to large-scale genomics datasets hold the promise to be major drivers for genome science. Once trained, such models can serve as a tool to probe the relationships between data modalities, including the effect of genetic variants on phenotype. However, lack of standardization and limited accessibility of trained models have hampered their impact in practice. To address this, we present Kipoi, a collaborative initiative to define standards and to foster reuse of trained models in genomics. Already, the Kipoi repository contains over 2,000 trained models that cover canonical prediction tasks in transcriptional and post-transcriptional gene regulation. The Kipoi model standard grants automated software installation and provides unified interfaces to apply and interpret models. We illustrate Kipoi through canonical use cases, including model benchmarking, transfer learning, variant effect prediction, and building new models from existing ones. By providing a unified framework to archive, share, access, use, and build on models developed by the community, Kipoi will foster the dissemination and use of machine learning models in genomics.

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 QUBO formulations for training machine learning models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Prasanna Date ◽  
Davis Arthur ◽  
Lauren Pusey-Nazzaro
Keyword(s):  
Machine Learning ◽  
Linear Regression ◽  
Large Scale ◽  
Support Vector ◽  
Quantum Computers ◽  
Np Hard ◽  
Learning Models ◽  
Moore’S Law ◽  
Moore's Law ◽  
Machine Learning Models

AbstractTraining machine learning models on classical computers is usually a time and compute intensive process. With Moore’s law nearing its inevitable end and an ever-increasing demand for large-scale data analysis using machine learning, we must leverage non-conventional computing paradigms like quantum computing to train machine learning models efficiently. Adiabatic quantum computers can approximately solve NP-hard problems, such as the quadratic unconstrained binary optimization (QUBO), faster than classical computers. Since many machine learning problems are also NP-hard, we believe adiabatic quantum computers might be instrumental in training machine learning models efficiently in the post Moore’s law era. In order to solve problems on adiabatic quantum computers, they must be formulated as QUBO problems, which is very challenging. In this paper, we formulate the training problems of three machine learning models—linear regression, support vector machine (SVM) and balanced k-means clustering—as QUBO problems, making them conducive to be trained on adiabatic quantum computers. We also analyze the computational complexities of our formulations and compare them to corresponding state-of-the-art classical approaches. We show that the time and space complexities of our formulations are better (in case of SVM and balanced k-means clustering) or equivalent (in case of linear regression) to their classical counterparts.

O-203 Application of machine learning to predict aneuploidy and mosaicism in embryos from in vitro fertilization (IVF) cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J A Ortiz ◽  
R Morales ◽  
B Lledo ◽  
E Garcia-Hernandez ◽  
A Cascales ◽  
...  
Keyword(s):  
Machine Learning ◽  
Predictive Model ◽  
Predictive Models ◽  
Maternal Age ◽  
The Other ◽  
Predictor Variables ◽  
Learning Models ◽  
Male Factor ◽  
Factors Associated ◽  
Machine Learning Models

Abstract Study question Is it possible to predict the likelihood of an IVF embryo being aneuploid and/or mosaic using a machine learning algorithm? Summary answer There are paternal, maternal, embryonic and IVF-cycle factors that are associated with embryonic chromosomal status that can be used as predictors in machine learning models. What is known already The factors associated with embryonic aneuploidy have been extensively studied. Mostly maternal age and to a lesser extent male factor and ovarian stimulation have been related to the occurrence of chromosomal alterations in the embryo. On the other hand, the main factors that may increase the incidence of embryo mosaicism have not yet been established. The models obtained using classical statistical methods to predict embryonic aneuploidy and mosaicism are not of high reliability. As an alternative to traditional methods, different machine and deep learning algorithms are being used to generate predictive models in different areas of medicine, including human reproduction. Study design, size, duration The study design is observational and retrospective. A total of 4654 embryos from 1558 PGT-A cycles were included (January-2017 to December-2020). The trophoectoderm biopsies on D5, D6 or D7 blastocysts were analysed by NGS. Embryos with ≤25% aneuploid cells were considered euploid, between 25-50% were classified as mosaic and aneuploid with &gt;50%. The variables of the PGT-A were recorded in a database from which predictive models of embryonic aneuploidy and mosaicism were developed. Participants/materials, setting, methods The main indications for PGT-A were advanced maternal age, abnormal sperm FISH and recurrent miscarriage or implantation failure. Embryo analysis were performed using Veriseq-NGS (Illumina). The software used to carry out all the analysis was R (RStudio). The library used to implement the different algorithms was caret. In the machine learning models, 22 predictor variables were introduced, which can be classified into 4 categories: maternal, paternal, embryonic and those specific to the IVF cycle. Main results and the role of chance The different couple, embryo and stimulation cycle variables were recorded in a database (22 predictor variables). Two different predictive models were performed, one for aneuploidy and the other for mosaicism. The predictor variable was of multi-class type since it included the segmental and whole chromosome alteration categories. The dataframe were first preprocessed and the different classes to be predicted were balanced. A 80% of the data were used for training the model and 20% were reserved for further testing. The classification algorithms applied include multinomial regression, neural networks, support vector machines, neighborhood-based methods, classification trees, gradient boosting, ensemble methods, Bayesian and discriminant analysis-based methods. The algorithms were optimized by minimizing the Log_Loss that measures accuracy but penalizing misclassifications. The best predictive models were achieved with the XG-Boost and random forest algorithms. The AUC of the predictive model for aneuploidy was 80.8% (Log_Loss 1.028) and for mosaicism 84.1% (Log_Loss: 0.929). The best predictor variables of the models were maternal age, embryo quality, day of biopsy and whether or not the couple had a history of pregnancies with chromosomopathies. The male factor only played a relevant role in the mosaicism model but not in the aneuploidy model. Limitations, reasons for caution Although the predictive models obtained can be very useful to know the probabilities of achieving euploid embryos in an IVF cycle, increasing the sample size and including additional variables could improve the models and thus increase their predictive capacity. Wider implications of the findings Machine learning can be a very useful tool in reproductive medicine since it can allow the determination of factors associated with embryonic aneuploidies and mosaicism in order to establish a predictive model for both. To identify couples at risk of embryo aneuploidy/mosaicism could benefit them of the use of PGT-A. Trial registration number Not Applicable

Machine Learning Predictive Models to Estimate the Minimum Miscibility Pressure of CO2-Oil System

2021 ◽  
Author(s):  
Abderraouf Chemmakh ◽  
Ahmed Merzoug ◽  
Habib Ouadi ◽  
Abdelhak Ladmia ◽  
Vamegh Rasouli
Keyword(s):  
Machine Learning ◽  
Predictive Models ◽  
Critical Parameters ◽  
Co2 Injection ◽  
Learning Models ◽  
Minimum Miscibility Pressure ◽  
Reservoir Conditions ◽  
Important Amount ◽  
Machine Learning Models

Abstract One of the most critical parameters of the CO2 injection (for EOR purposes) is the Minimum Miscibility Pressure MMP. The determination of this parameter is crucial for the success of the operation. Different experimental, analytical, and statistical technics are used to predict the MMP. Nevertheless, experimental technics are costly and tedious, while correlations are used for specific reservoir conditions. Based on that, the purpose of this paper is to build machine learning models aiming to predict the MMP efficiently and in broad-based reservoir conditions. Two ML models are proposed for both pure CO2 and non-pure CO2 injection. An important amount of data collected from literature is used in this work. The ANN and SVR-GA models have shown enhanced performance comparing to existing correlations in literature for both the pure and non-pure models, with a coefficient of R2 0.98, 0.93 and 0.96, 0.93 respectively, which confirms that the proposed models are reliable and ready to use.

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 Comparison of Resampling Algorithms to Address Class Imbalance when Developing Machine Learning Models to Predict Foodborne Pathogen Presence in Agricultural Water

2021 ◽  
Vol 9 ◽  
Author(s):  
Daniel Lowell Weller ◽  
Tanzy M. T. Love ◽  
Martin Wiedmann
Keyword(s):  
Machine Learning ◽  
Random Forest ◽  
Predictive Models ◽  
Training Data ◽  
Agricultural Water ◽  
Learning Models ◽  
Safety Hazards ◽  
E Coli ◽  
Resampling Method ◽  
Machine Learning Models

Recent studies have shown that predictive models can supplement or provide alternatives to E. coli-testing for assessing the potential presence of food safety hazards in water used for produce production. However, these studies used balanced training data and focused on enteric pathogens. As such, research is needed to determine 1) if predictive models can be used to assess Listeria contamination of agricultural water, and 2) how resampling (to deal with imbalanced data) affects performance of these models. To address these knowledge gaps, this study developed models that predict nonpathogenic Listeria spp. (excluding L. monocytogenes) and L. monocytogenes presence in agricultural water using various combinations of learner (e.g., random forest, regression), feature type, and resampling method (none, oversampling, SMOTE). Four feature types were used in model training: microbial, physicochemical, spatial, and weather. “Full models” were trained using all four feature types, while “nested models” used between one and three types. In total, 45 full (15 learners*3 resampling approaches) and 108 nested (5 learners*9 feature sets*3 resampling approaches) models were trained per outcome. Model performance was compared against baseline models where E. coli concentration was the sole predictor. Overall, the machine learning models outperformed the baseline E. coli models, with random forests outperforming models built using other learners (e.g., rule-based learners). Resampling produced more accurate models than not resampling, with SMOTE models outperforming, on average, oversampling models. Regardless of resampling method, spatial and physicochemical water quality features drove accurate predictions for the nonpathogenic Listeria spp. and L. monocytogenes models, respectively. Overall, these findings 1) illustrate the need for alternatives to existing E. coli-based monitoring programs for assessing agricultural water for the presence of potential food safety hazards, and 2) suggest that predictive models may be one such alternative. Moreover, these findings provide a conceptual framework for how such models can be developed in the future with the ultimate aim of developing models that can be integrated into on-farm risk management programs. For example, future studies should consider using random forest learners, SMOTE resampling, and spatial features to develop models to predict the presence of foodborne pathogens, such as L. monocytogenes, in agricultural water when the training data is imbalanced.

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