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Prediction Model of Clearance by a Novel Quantitative Structure-Activity Relationship Approach, Combination DeepSnap-Deep Learning and Conventional Machine Learning.

ABSTRACT: Some targets predicted by machine learning (ML) in drug discovery remain a challenge because of poor prediction. In this study, a new prediction model was developed and rat clearance (CL) was selected as a target because it is difficult to predict. A classification model was constructed using 1545 in-house compounds with rat CL data. The molecular descriptors calculated by Molecular Operating Environment (MOE), alvaDesc, and ADMET Predictor software were used to construct the prediction model. In conventional ML using 100 descriptors and random forest selected by DataRobot, the area under the curve (AUC) and accuracy (ACC) were 0.883 and 0.825, respectively. Conversely, the prediction model using DeepSnap and Deep Learning (DeepSnap-DL) with compound features as images had AUC and ACC of 0.905 and 0.832, respectively. We combined the two models (conventional ML and DeepSnap-DL) to develop a novel prediction model. Using the ensemble model with the mean of the predicted probabilities from each model improved the evaluation metrics (AUC = 0.943 and ACC = 0.874). In addition, a consensus model using the results of the agreement between classifications had an increased ACC (0.959). These combination models with a high level of predictive performance can be applied to rat CL as well as other pharmacokinetic parameters, pharmacological activity, and toxicity prediction. Therefore, these models will aid in the design of more rational compounds for the development of drugs.

SUBMITTER: Mamada H

PROVIDER: S-EPMC8444299 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRadiomics can provide in-depth characterization of cancers for treatment outcome prediction. Conventional radiomics rely on extraction of image features within a pre-defined image region of interest (ROI) which are typically fed to a classification algorithm for prediction of a clinical endpoint. Deep learning radiomics allows for a simpler workflow where images can be used directly as input to a convolutional neural network (CNN) with or without a pre-defined ROI.PurposeThe purpose of this study was to evaluate (i) conventional radiomics and (ii) deep learning radiomics for predicting overall survival (OS) and disease-free survival (DFS) for patients with head and neck squamous cell carcinoma (HNSCC) using pre-treatment 18F-fluorodeoxuglucose positron emission tomography (FDG PET) and computed tomography (CT) images.Materials and methodsFDG PET/CT images and clinical data of patients with HNSCC treated with radio(chemo)therapy at Oslo University Hospital (OUS; n = 139) and Maastricht University Medical Center (MAASTRO; n = 99) were collected retrospectively. OUS data was used for model training and initial evaluation. MAASTRO data was used for external testing to assess cross-institutional generalizability. Models trained on clinical and/or conventional radiomics features, with or without feature selection, were compared to CNNs trained on PET/CT images without or with the gross tumor volume (GTV) included. Model performance was measured using accuracy, area under the receiver operating characteristic curve (AUC), Matthew's correlation coefficient (MCC), and the F1 score calculated for both classes separately.ResultsCNNs trained directly on images achieved the highest performance on external data for both endpoints. Adding both clinical and radiomics features to these image-based models increased performance further. Conventional radiomics including clinical data could achieve competitive performance. However, feature selection on clinical and radiomics data lead to overfitting and poor cross-institutional generalizability. CNNs without tumor and node contours achieved close to on-par performance with CNNs including contours.ConclusionHigh performance and cross-institutional generalizability can be achieved by combining clinical data, radiomics features and medical images together with deep learning models. However, deep learning models trained on images without contours can achieve competitive performance and could see potential use as an initial screening tool for high-risk patients.

Project description:This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer Neurodegenerative Diseases Biobank data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar area-under-the-curve (AUC) for SVM (0.940; 95%CI: 0.924-0.955) and CNN (0.933; 95%CI: 0.918-0.948). Application to conversion prediction in MCI yielded significantly higher performance for SVM (AUC = 0.756; 95%CI: 0.720-0.788) than for CNN (AUC = 0.742; 95%CI: 0.709-0.776) (p<0.01 for McNemar's test). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896; 95%CI: 0.855-0.932) and CNN (0.876; 95%CI: 0.836-0.913). For prediction in MCI, performances decreased for both SVM (AUC = 0.665; 95%CI: 0.576-0.760) and CNN (AUC = 0.702; 95%CI: 0.624-0.786). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images (p=0.01). Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.

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Prediction Model of Clearance by a Novel Quantitative Structure-Activity Relationship Approach, Combination DeepSnap-Deep Learning and Conventional Machine Learning.

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