Dataset Information

Classification of estrogenic compounds by coupling high content analysis and machine learning algorithms.

ABSTRACT: Environmental toxicants affect human health in various ways. Of the thousands of chemicals present in the environment, those with adverse effects on the endocrine system are referred to as endocrine-disrupting chemicals (EDCs). Here, we focused on a subclass of EDCs that impacts the estrogen receptor (ER), a pivotal transcriptional regulator in health and disease. Estrogenic activity of compounds can be measured by many in vitro or cell-based high throughput assays that record various endpoints from large pools of cells, and increasingly at the single-cell level. To simultaneously capture multiple mechanistic ER endpoints in individual cells that are affected by EDCs, we previously developed a sensitive high throughput/high content imaging assay that is based upon a stable cell line harboring a visible multicopy ER responsive transcription unit and expressing a green fluorescent protein (GFP) fusion of ER. High content analysis generates voluminous multiplex data comprised of minable features that describe numerous mechanistic endpoints. In this study, we present a machine learning pipeline for rapid, accurate, and sensitive assessment of the endocrine-disrupting potential of benchmark chemicals based on data generated from high content analysis. The multidimensional imaging data was used to train a classification model to ultimately predict the impact of unknown compounds on the ER, either as agonists or antagonists. To this end, both linear logistic regression and nonlinear Random Forest classifiers were benchmarked and evaluated for predicting the estrogenic activity of unknown compounds. Furthermore, through feature selection, data visualization, and model discrimination, the most informative features were identified for the classification of ER agonists/antagonists. The results of this data-driven study showed that highly accurate and generalized classification models with a minimum number of features can be constructed without loss of generality, where these machine learning models serve as a means for rapid mechanistic/phenotypic evaluation of the estrogenic potential of many chemicals.

SUBMITTER: Mukherjee R

PROVIDER: S-EPMC7538107 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Classification of estrogenic compounds by coupling high content analysis and machine learning algorithms.

Mukherjee Rajib R Beykal Burcu B Szafran Adam T AT Onel Melis M Stossi Fabio F Mancini Maureen G MG Lloyd Dillon D Wright Fred A FA Zhou Lan L Mancini Michael A MA Pistikopoulos Efstratios N EN

PLoS computational biology 20200924 9

Environmental toxicants affect human health in various ways. Of the thousands of chemicals present in the environment, those with adverse effects on the endocrine system are referred to as endocrine-disrupting chemicals (EDCs). Here, we focused on a subclass of EDCs that impacts the estrogen receptor (ER), a pivotal transcriptional regulator in health and disease. Estrogenic activity of compounds can be measured by many in vitro or cell-based high throughput assays that record various endpoints ...[more]

PMID: 32970665

Similar Datasets

Project description:The objective of this work was to perform image-based classification of abdominal aortic aneurysms (AAA) based on their demographic, geometric, and biomechanical attributes. We retrospectively reviewed existing demographics and abdominal computed tomography angiography images of 100 asymptomatic and 50 symptomatic AAA patients who received an elective or emergent repair, respectively, within 1-6 months of their last follow up. An in-house script developed within the MATLAB computational platform was used to segment the clinical images, calculate 53 descriptors of AAA geometry, and generate volume meshes suitable for finite element analysis (FEA). Using a third party FEA solver, four biomechanical markers were calculated from the wall stress distributions. Eight machine learning algorithms (MLA) were used to develop classification models based on the discriminatory potential of the demographic, geometric, and biomechanical variables. The overall classification performance of the algorithms was assessed by the accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and precision of their predictions. The generalized additive model (GAM) was found to have the highest accuracy (87%), AUC (89%), and sensitivity (78%), and the third highest specificity (92%), in classifying the individual AAA as either asymptomatic or symptomatic. The k-nearest neighbor classifier yielded the highest specificity (96%). GAM used seven markers (six geometric and one biomechanical) to develop the classifier. The maximum transverse dimension, the average wall thickness at the maximum diameter, and the spatially averaged wall stress were found to be the most influential markers in the classification analysis. A second classification analysis revealed that using maximum diameter alone results in a lower accuracy (79%) than using GAM with seven geometric and biomechanical markers. We infer from these results that biomechanical and geometric measures by themselves are not sufficient to discriminate adequately between population samples of asymptomatic and symptomatic AAA, whereas MLA offer a statistical approach to stratification of rupture risk by combining demographic, geometric, and biomechanical attributes of patient-specific AAA.

Project description:Microbial communities play key roles in ocean ecosystems through regulation of biogeochemical processes such as carbon and nutrient cycling, food web dynamics, and gut microbiomes of invertebrates, fish, reptiles, and mammals. Assessments of marine microbial diversity are therefore critical to understanding spatiotemporal variations in microbial community structure and function in ocean ecosystems. With recent advances in DNA shotgun sequencing for metagenome samples and computational analysis, it is now possible to access the taxonomic and genomic content of ocean microbial communities to study their structural patterns, diversity, and functional potential. However, existing taxonomic classification tools depend upon manually curated phylogenetic trees, which can create inaccuracies in metagenomes from less well-characterized communities, such as from ocean water. Herein, we explore the utility of deep learning tools-DeepMicrobes and a novel Residual Network architecture-that leverage natural language processing and convolutional neural network architectures to map input sequence data (k-mers) to output labels (taxonomic groups) without reliance on a curated taxonomic tree. We trained both models using metagenomic reads simulated from marine microbial genomes in the MarRef database. The performance of both models (accuracy, precision, and percent microbe predicted) was compared with the standard taxonomic classification tool Kraken2 using 10 complex metagenomic data sets simulated from MarRef. Our results demonstrate that time, compute power, and microbial genomic diversity still pose challenges for machine learning (ML). Moreover, our results suggest that high genome coverage and rectification of class imbalance are prerequisites for a well-trained model, and therefore should be a major consideration in future ML work. IMPORTANCE Taxonomic profiling of microbial communities is essential to model microbial interactions and inform habitat conservation. This work develops approaches in constructing training/testing data sets from publicly available marine metagenomes and evaluates the performance of machine learning (ML) approaches in read-based taxonomic classification of marine metagenomes. Predictions from two models are used to test accuracy in metagenomic classification and to guide improvements in ML approaches. Our study provides insights on the methods, results, and challenges of deep learning on marine microbial metagenomic data sets. Future machine learning approaches can be improved by rectifying genome coverage and class imbalance in the training data sets, developing alternative models, and increasing the accessibility of computational resources for model training and refinement.

Dataset Information

Classification of estrogenic compounds by coupling high content analysis and machine learning algorithms.

Publications

Classification of estrogenic compounds by coupling high content analysis and machine learning algorithms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets