Dataset Information

MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

ABSTRACT: BACKGROUND:DNA methylation (DNAm) is an epigenetic regulator of gene expression programs that can be altered by environmental exposures, aging, and in pathogenesis. Traditional analyses that associate DNAm alterations with phenotypes suffer from multiple hypothesis testing and multi-collinearity due to the high-dimensional, continuous, interacting and non-linear nature of the data. Deep learning analyses have shown much promise to study disease heterogeneity. DNAm deep learning approaches have not yet been formalized into user-friendly frameworks for execution, training, and interpreting models. Here, we describe MethylNet, a DNAm deep learning method that can construct embeddings, make predictions, generate new data, and uncover unknown heterogeneity with minimal user supervision. RESULTS:The results of our experiments indicate that MethylNet can study cellular differences, grasp higher order information of cancer sub-types, estimate age and capture factors associated with smoking in concordance with known differences. CONCLUSION:The ability of MethylNet to capture nonlinear interactions presents an opportunity for further study of unknown disease, cellular heterogeneity and aging processes.

SUBMITTER: Levy JJ

PROVIDER: S-EPMC7076991 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

Levy Joshua J JJ Titus Alexander J AJ Petersen Curtis L CL Chen Youdinghuan Y Salas Lucas A LA Christensen Brock C BC

BMC bioinformatics 20200317 1

<h4>Background</h4>DNA methylation (DNAm) is an epigenetic regulator of gene expression programs that can be altered by environmental exposures, aging, and in pathogenesis. Traditional analyses that associate DNAm alterations with phenotypes suffer from multiple hypothesis testing and multi-collinearity due to the high-dimensional, continuous, interacting and non-linear nature of the data. Deep learning analyses have shown much promise to study disease heterogeneity. DNAm deep learning approache ...[more]

PMID: 32183722

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Project description:Purpose: To assess the accuracy and efficacy of a semi-automated deep learning algorithm (DLA) assisted approach to detect vision-threatening diabetic retinopathy (DR). Methods: We developed a two-step semi-automated DLA-assisted approach to grade fundus photographs for vision-threatening referable DR. Study images were obtained from the Lingtou Cohort Study, and captured at participant enrollment in 2009-2010 ("baseline images") and annual follow-up between 2011 and 2017. To begin, a validated DLA automatically graded baseline images for referable DR and classified them as positive, negative, or ungradable. Following, each positive image, all other available images from patients who had a positive image, and a 5% random sample of all negative images were selected and regraded by trained human graders. A reference standard diagnosis was assigned once all graders achieved consistent grading outcomes or with a senior ophthalmologist's final diagnosis. The semi-automated DLA assisted approach combined initial DLA screening and subsequent human grading for images identified as high-risk. This approach was further validated within the follow-up image datasets and its time and economic costs evaluated against fully human grading. Results: For evaluation of baseline images, a total of 33,115 images were included and automatically graded by the DLA. 2,604 images (480 positive results, 624 available other images from participants with a positive result, and 1500 random negative samples) were selected and regraded by graders. The DLA achieved an area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.953, 0.970, 0.879, and 88.6%, respectively. In further validation within the follow-up image datasets, a total of 88,363 images were graded using this semi-automated approach and human grading was performed on 8975 selected images. The DLA achieved an AUC, sensitivity, and specificity of 0.914, 0.852, 0.853, respectively. Compared against fully human grading, the semi-automated DLA-assisted approach achieved an estimated 75.6% time and 90.1% economic cost saving. Conclusions: The DLA described in this study was able to achieve high accuracy, sensitivity, and specificity in grading fundus images for referable DR. Validated against long-term follow-up datasets, a semi-automated DLA-assisted approach was able to accurately identify suspect cases, and minimize misdiagnosis whilst balancing safety, time, and economic cost.

Project description:PURPOSE:To assess the utility of deep learning in the detection of geographic atrophy (GA) from color fundus photographs and to explore potential utility in detecting central GA (CGA). DESIGN:A deep learning model was developed to detect the presence of GA in color fundus photographs, and 2 additional models were developed to detect CGA in different scenarios. PARTICIPANTS:A total of 59?812 color fundus photographs from longitudinal follow-up of 4582 participants in the Age-Related Eye Disease Study (AREDS) dataset. Gold standard labels were from human expert reading center graders using a standardized protocol. METHODS:A deep learning model was trained to use color fundus photographs to predict GA presence from a population of eyes with no AMD to advanced AMD. A second model was trained to predict CGA presence from the same population. A third model was trained to predict CGA presence from the subset of eyes with GA. For training and testing, 5-fold cross-validation was used. For comparison with human clinician performance, model performance was compared with that of 88 retinal specialists. MAIN OUTCOME MEASURES:Area under the curve (AUC), accuracy, sensitivity, specificity, and precision. RESULTS:The deep learning models (GA detection, CGA detection from all eyes, and centrality detection from GA eyes) had AUCs of 0.933-0.976, 0.939-0.976, and 0.827-0.888, respectively. The GA detection model had accuracy, sensitivity, specificity, and precision of 0.965 (95% confidence interval [CI], 0.959-0.971), 0.692 (0.560-0.825), 0.978 (0.970-0.985), and 0.584 (0.491-0.676), respectively, compared with 0.975 (0.971-0.980), 0.588 (0.468-0.707), 0.982 (0.978-0.985), and 0.368 (0.230-0.505) for the retinal specialists. The CGA detection model had values of 0.966 (0.957-0.975), 0.763 (0.641-0.885), 0.971 (0.960-0.982), and 0.394 (0.341-0.448). The centrality detection model had values of 0.762 (0.725-0.799), 0.782 (0.618-0.945), 0.729 (0.543-0.916), and 0.799 (0.710-0.888). CONCLUSIONS:A deep learning model demonstrated high accuracy for the automated detection of GA. The AUC was noninferior to that of human retinal specialists. Deep learning approaches may also be applied to the identification of CGA. The code and pretrained models are publicly available at https://github.com/ncbi-nlp/DeepSeeNet.

Dataset Information

MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

Publications

MethylNet: an automated and modular deep learning approach for DNA methylation analysis.

Similar Datasets

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