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A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease.

ABSTRACT: Next-generation sequencing (NGS) technology has become a powerful tool for dissecting the molecular and pathological signatures of a variety of human diseases. However, the limited availability of biological samples from different disease stages is a major hurdle in studying disease progressions and identifying early pathological changes. Deep learning techniques have recently begun to be applied to analyze NGS data and thereby predict the progression of biological processes. In this study, we applied a deep learning technique called generative adversarial networks (GANs) to predict the molecular progress of Alzheimer's disease (AD). We successfully applied GANs to analyze RNA-seq data from a 5xFAD mouse model of AD, which recapitulates major AD features of massive amyloid-? (A?) accumulation in the brain. We examined how the generator is featured to have specific-sample generation and biological gene association. Based on the above observations, we suggested virtual disease progress by latent space interpolation to yield the transition curves of various genes with pathological changes from normal to AD state. By performing pathway analysis based on the transition curve patterns, we identified several pathological processes with progressive changes, such as inflammatory systems and synapse functions, which have previously been demonstrated to be involved in the pathogenesis of AD. Interestingly, our analysis indicates that alteration of cholesterol biosynthesis begins at a very early stage of AD, suggesting that it is the first effect to mediate the cholesterol metabolism of AD downstream of A? accumulation. Here, we suggest that GANs are a useful tool to study disease progression, leading to the identification of early pathological signatures.

SUBMITTER: Park J

PROVIDER: S-EPMC7406107 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease.

Park Jinhee J Kim Hyerin H Kim Jaekwang J Cheon Mookyung M

PLoS computational biology 20200724 7

Next-generation sequencing (NGS) technology has become a powerful tool for dissecting the molecular and pathological signatures of a variety of human diseases. However, the limited availability of biological samples from different disease stages is a major hurdle in studying disease progressions and identifying early pathological changes. Deep learning techniques have recently begun to be applied to analyze NGS data and thereby predict the progression of biological processes. In this study, we a ...[more]

PMID: 32706788

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Project description:PurposeComplementary information obtained from multiple contrasts of tissue facilitates physicians assessing, diagnosing and planning treatment of a variety of diseases. However, acquiring multiple contrasts magnetic resonance images (MRI) for every patient using multiple pulse sequences is time-consuming and expensive, where, medical image synthesis has been demonstrated as an effective alternative. The purpose of this study is to develop a unified framework for multimodal MR image synthesis.MethodsA unified generative adversarial network consisting of only a single generator and a single discriminator was developed to learn the mappings among images of four different modalities. The generator took an image and its modality label as inputs and learned to synthesize the image in the target modality, while the discriminator was trained to distinguish between real and synthesized images and classify them to their corresponding modalities. The network was trained and tested using multimodal brain MRI consisting of four different contrasts which are T1-weighted (T1), T1-weighted and contrast-enhanced (T1c), T2-weighted (T2), and fluid-attenuated inversion recovery (Flair). Quantitative assessments of our proposed method were made through computing normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR), structural similarity index measurement (SSIM), visual information fidelity (VIF), and naturalness image quality evaluator (NIQE).ResultsThe proposed model was trained and tested on a cohort of 274 glioma patients with well-aligned multi-types of MRI scans. After the model was trained, tests were conducted by using each of T1, T1c, T2, Flair as a single input modality to generate its respective rest modalities. Our proposed method shows high accuracy and robustness for image synthesis with arbitrary MRI modality that is available in the database as input. For example, with T1 as input modality, the NMAEs for the generated T1c, T2, Flair respectively are 0.034 ± 0.005, 0.041 ± 0.006, and 0.041 ± 0.006, the PSNRs respectively are 32.353 ± 2.525 dB, 30.016 ± 2.577 dB, and 29.091 ± 2.795 dB, the SSIMs are 0.974 ± 0.059, 0.969 ± 0.059, and 0.959 ± 0.059, the VIF are 0.750 ± 0.087, 0.706 ± 0.097, and 0.654 ± 0.062, and NIQE are 1.396 ± 0.401, 1.511 ± 0.460, and 1.259 ± 0.358, respectively.ConclusionsWe proposed a novel multimodal MR image synthesis method based on a unified generative adversarial network. The network takes an image and its modality label as inputs and synthesizes multimodal images in a single forward pass. The results demonstrate that the proposed method is able to accurately synthesize multimodal MR images from a single MR image.

Dataset Information

A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease.

Publications

A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease.

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