Machine learning models for classification tasks related to drug safety.
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ABSTRACT:
SUBMITTER: Racz A
PROVIDER: S-EPMC8342376 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent trends in drug development have been marked by diminishing returns caused by the escalating costs and falling rates of new drug approval. Unacceptable drug toxicity is a substantial cause of drug failure during clinical trials and the leading cause of drug withdraws after release to the market. Computational methods capable of predicting these failures can reduce the waste of resources and time devoted to the investigation of compounds that ultimately fail. We propose an original machine learning method that leverages identity of drug targets and off-targets, functional impact score computed from Gene Ontology annotations, and biological network data to predict drug toxicity. We demonstrate that our method (TargeTox) can distinguish potentially idiosyncratically toxic drugs from safe drugs and is also suitable for speculative evaluation of different target sets to support the design of optimal low-toxicity combinations.
| S-EPMC6262234 | biostudies-literature
Project description:Herein, we implement and access machine learning architectures to ascertain models that differentiate healthy from apoptotic cells using exclusively forward (FSC) and side (SSC) scatter flow cytometry information. To generate training data, colorectal cancer HCT116 cells were subjected to miR-34a treatment and then classified using a conventional Annexin V/propidium iodide (PI)-staining assay. The apoptotic cells were defined as Annexin V-positive cells, which include early and late apoptotic cells, necrotic cells, as well as other dying or dead cells. In addition to fluorescent signal, we collected cell size and granularity information from the FSC and SSC parameters. Both parameters are subdivided into area, height, and width, thus providing a total of six numerical features that informed and trained our models. A collection of logistical regression, random forest, k-nearest neighbor, multilayer perceptron, and support vector machine was trained and tested for classification performance in predicting cell states using only the six aforementioned numerical features. Out of 1046 candidate models, a multilayer perceptron was chosen with 0.91 live precision, 0.93 live recall, 0.92 live f value and 0.97 live area under the ROC curve when applied on standardized data. We discuss and highlight differences in classifier performance and compare the results to the standard practice of forward and side scatter gating, typically performed to select cells based on size and/or complexity. We demonstrate that our model, a ready-to-use module for any flow cytometry-based analysis, can provide automated, reliable, and stain-free classification of healthy and apoptotic cells using exclusively size and granularity information.
| S-EPMC8155075 | biostudies-literature
Project description:We consider whether a deep neural network trained with raw MEG data can be used to predict the age of children performing a verb-generation task, a monosyllable speech-elicitation task, and a multi-syllabic speech-elicitation task. Furthermore, we argue that the network makes predictions on the grounds of differences in speech development. Previous work has explored taking 'deep' neural networks (DNNs) designed for, or trained with, images to classify encephalographic recordings with some success, but this does little to acknowledge the structure of these data. Simple neural networks have been used extensively to classify data expressed as features, but require extensive feature engineering and pre-processing. We present novel DNNs trained using raw magnetoencephalography (MEG) and electroencephalography (EEG) recordings that mimic the feature-engineering pipeline. We highlight criteria the networks use, including relative weighting of channels and preferred spectro-temporal characteristics of re-weighted channels. Our data feature 92 subjects aged 4-18, recorded using a 151-channel MEG system. Our proposed model scores over 95% mean cross-validation accuracy distinguishing above and below 10 years of age in single trials of un-seen subjects, and can classify publicly available EEG with state-of-the-art accuracy.
| S-EPMC6367450 | biostudies-literature
Project description:Since the last published update in 2014, the SuperPred webserver has been continuously developed to offer state-of-the-art models for drug classification according to ATC classes and target prediction. For the first time, a thoroughly filtered ATC dataset, that is suitable for accurate predictions, is provided along with detailed information on the achieved predictions. This aims to overcome the challenges in comparing different published prediction methods, since performance can vary greatly depending on the training dataset used. Additionally, both ATC and target prediction have been reworked and are now based on machine learning models instead of overall structural similarity, stressing the importance of functional groups for the mechanism of action of small molecule substances. Additionally, the dataset for the target prediction has been extensively filtered and is no longer only based on confirmed binders but also includes non-binding substances to reduce false positives. Using these methods, accuracy for the ATC prediction could be increased by almost 5% to 80.5% compared to the previous version, and additionally the scoring function now offers values which are easily assessable at first glance. SuperPred 3.0 is publicly available without the need for registration at: https://prediction.charite.de/index.php.
| S-EPMC9252837 | biostudies-literature
Project description:Single nucleotide polymorphisms (SNPs) can be used as inputs in disease computational studies such as pattern searching and classification models. Schizophrenia is an example of a complex disease with an important social impact. The multiple causes of this disease create the need of new genetic or proteomic patterns that can diagnose patients using biological information. This work presents a computational study of disease machine learning classification models using only single nucleotide polymorphisms at the HTR2A and DRD3 genes from Galician (Northwest Spain) schizophrenic patients. These classification models establish for the first time, to the best knowledge of the authors, a relationship between the sequence of the nucleic acid molecule and schizophrenia (Quantitative Genotype-Disease Relationships) that can automatically recognize schizophrenia DNA sequences and correctly classify between 78.3-93.8% of schizophrenia subjects when using datasets which include simulated negative subjects and a linear artificial neural network.
| S-EPMC6257637 | biostudies-literature
Project description:Triple negative breast cancer (TNBC) lacks well-defined molecular targets and is highly heterogenous, making treatment challenging. Using gene expression analysis, TNBC has been classified into four different subtypes: basal-like immune-activated (BLIA), basal-like immune-suppressed (BLIS), mesenchymal (MES), and luminal androgen receptor (LAR). However, there is currently no standardized method for classifying TNBC subtypes. We attempted to define a gene signature for each subtype, and to develop a classification method based on machine learning (ML) for TNBC subtyping. In these experiments, gene expression microarray data for TNBC patients were downloaded from the Gene Expression Omnibus database. Differentially expressed genes unique to 198 known TNBC cases were identified and selected as a training gene set to train in seven different classification models. We produced a training set consisting of 719 DEGs selected from uniquely expressed genes of all four subtypes. The highest average accuracy of classification of the BLIA, BLIS, MES, and LAR subtypes was achieved by the SVM algorithm (accuracy 95-98.8%; AUC 0.99-1.00). For model validation, we used 334 samples of unknown TNBC subtypes, of which 97 (29.04%), 73 (21.86%), 39 (11.68%) and 59 (17.66%) were predicted to be BLIA, BLIS, MES, and LAR, respectively. However, 66 TNBC samples (19.76%) could not be assigned to any subtype. These samples contained only three upregulated genes (EN1, PROM1, and CCL2). Each TNBC subtype had a unique gene expression pattern, which was confirmed by identification of DEGs and pathway analysis. These results indicated that our training gene set was suitable for development of classification models, and that the SVM algorithm could classify TNBC into four unique subtypes. Accurate and consistent classification of the TNBC subtypes is essential for personalized treatment and prognosis of TNBC.
| S-EPMC8472680 | biostudies-literature
Project description:BackgroundControlling the COVID-19 outbreak in Brazil is a challenge due to the population's size and urban density, inefficient maintenance of social distancing and testing strategies, and limited availability of testing resources.ObjectiveThe purpose of this study is to effectively prioritize patients who are symptomatic for testing to assist early COVID-19 detection in Brazil, addressing problems related to inefficient testing and control strategies.MethodsRaw data from 55,676 Brazilians were preprocessed, and the chi-square test was used to confirm the relevance of the following features: gender, health professional, fever, sore throat, dyspnea, olfactory disorders, cough, coryza, taste disorders, and headache. Classification models were implemented relying on preprocessed data sets; supervised learning; and the algorithms multilayer perceptron (MLP), gradient boosting machine (GBM), decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost), k-nearest neighbors (KNN), support vector machine (SVM), and logistic regression (LR). The models' performances were analyzed using 10-fold cross-validation, classification metrics, and the Friedman and Nemenyi statistical tests. The permutation feature importance method was applied for ranking the features used by the classification models with the highest performances.ResultsGender, fever, and dyspnea were among the highest-ranked features used by the classification models. The comparative analysis presents MLP, GBM, DT, RF, XGBoost, and SVM as the highest performance models with similar results. KNN and LR were outperformed by the other algorithms. Applying the easy interpretability as an additional comparison criterion, the DT was considered the most suitable model.ConclusionsThe DT classification model can effectively (with a mean accuracy≥89.12%) assist COVID-19 test prioritization in Brazil. The model can be applied to recommend the prioritizing of a patient who is symptomatic for COVID-19 testing.
| S-EPMC8034680 | biostudies-literature
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.
| S-EPMC6167198 | biostudies-literature
Project description:Classification and quantitative characterization of neuronal morphologies from histological neuronal reconstruction is challenging since it is still unclear how to delineate a neuronal cell class and which are the best features to define them by. The morphological neuron characterization represents a primary source to address anatomical comparisons, morphometric analysis of cells, or brain modeling. The objectives of this paper are (i) to develop and integrate a pipeline that goes from morphological feature extraction to classification and (ii) to assess and compare the accuracy of machine learning algorithms to classify neuron morphologies. The algorithms were trained on 430 digitally reconstructed neurons subjectively classified into layers and/or m-types using young and/or adult development state population of the somatosensory cortex in rats. For supervised algorithms, linear discriminant analysis provided better classification results in comparison with others. For unsupervised algorithms, the affinity propagation and the Ward algorithms provided slightly better results.
| S-EPMC5088188 | biostudies-literature
Project description:OBJECTIVE:The ability to monitor anesthetic states using automated approaches is expected to reduce inaccurate drug dosing and side-effects. Commercially available anesthetic state monitors perform poorly when ketamine is administered as an anesthetic-analgesic adjunct. Poor performance is likely because the models underlying these monitors are not optimized for the electroencephalogram (EEG) oscillations that are unique to the co-administration of ketamine. APPROACH:In this work, we designed two k-nearest neighbors algorithms for anesthetic state prediction. MAIN RESULTS:The first algorithm was trained only on sevoflurane EEG data, making it sevoflurane-specific. This algorithm enabled discrimination of the sevoflurane general anesthesia (GA) state from sedated and awake states (true positive rate = 0.87, [95% CI, 0.76, 0.97]). However, it did not enable discrimination of the sevoflurane-plus-ketamine GA state from sedated and awake states (true positive rate = 0.43, [0.19, 0.67]). In our second algorithm, we implemented a cross drug training paradigm by including both sevoflurane and sevoflurane-plus-ketamine EEG data in our training set. This algorithm enabled discrimination of the sevoflurane-plus-ketamine GA state from sedated and awake states (true positive rate = 0.91, [0.84, 0.98]). SIGNIFICANCE:Instead of a one-algorithm-fits-all-drugs approach to anesthetic state monitoring, our results suggest that drug-specific models are necessary to improve the performance of automated anesthetic state monitors.
| S-EPMC7540939 | biostudies-literature