Dataset Information

Unveiling new disease, pathway, and gene associations via multi-scale neural network.

ABSTRACT: Diseases involve complex modifications to the cellular machinery. The gene expression profile of the affected cells contains characteristic patterns linked to a disease. Hence, new biological knowledge about a disease can be extracted from these profiles, improving our ability to diagnose and assess disease risks. This knowledge can be used for drug re-purposing, or by physicians to evaluate a patient's condition and co-morbidity risk. Here, we consider differential gene expressions obtained by microarray technology for patients diagnosed with various diseases. Based on these data and cellular multi-scale organization, we aim at uncovering disease-disease, disease-gene and disease-pathway associations. We propose a neural network with structure based on the multi-scale organization of proteins in a cell into biological pathways. We show that this model is able to correctly predict the diagnosis for the majority of patients. Through the analysis of the trained model, we predict disease-disease, disease-pathway, and disease-gene associations and validate the predictions by comparisons to known interactions and literature search, proposing putative explanations for the predictions.

SUBMITTER: Gaudelet T

PROVIDER: S-EPMC7135208 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Unveiling new disease, pathway, and gene associations via multi-scale neural network.

Gaudelet Thomas T Malod-Dognin Noël N Sánchez-Valle Jon J Pancaldi Vera V Valencia Alfonso A Pržulj Nataša N

PloS one 20200406 4

Diseases involve complex modifications to the cellular machinery. The gene expression profile of the affected cells contains characteristic patterns linked to a disease. Hence, new biological knowledge about a disease can be extracted from these profiles, improving our ability to diagnose and assess disease risks. This knowledge can be used for drug re-purposing, or by physicians to evaluate a patient's condition and co-morbidity risk. Here, we consider differential gene expressions obtained by ...[more]

PMID: 32251458

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Project description:In this study, we developed a multi-scale Convolutional neural network based Automated hippocampal subfield Segmentation Toolbox (CAST) for automated segmentation of hippocampal subfields. Although training CAST required approximately three days on a single workstation with a high-quality GPU card, CAST can segment a new subject in less than 1 min even with GPU acceleration disabled, thus this method is more time efficient than current automated methods and manual segmentation. This toolbox is highly flexible with either a single modality or multiple modalities and can be easily set up to be trained with a researcher's unique data. A 3D multi-scale deep convolutional neural network is the key algorithm used in the toolbox. The main merit of multi-scale images is the capability to capture more global structural information from down-sampled images without dramatically increasing memory and computational burden. The original images capture more local information to refine the boundary between subfields. Residual learning is applied to alleviate the vanishing gradient problem and improve the performance with a deeper network. We applied CAST with the same settings on two datasets, one 7T dataset (the UMC dataset) with only the T2 image and one 3T dataset (the MNI dataset) with both T1 and T2 images available. The segmentation accuracy of both CAST and the state-of-the-art automated method ASHS, in terms of the dice similarity coefficient (DSC), were comparable. CAST significantly improved the reliability of segmenting small subfields, such as CA2, CA3, and the entorhinal cortex (ERC), in terms of the intraclass correlation coefficient (ICC). Both ASHS and manual segmentation process some subfields (e.g. CA2 and ERC) with high DSC values but low ICC values, consequently increasing the difficulty of judging segmentation quality. CAST produces very consistent DSC and ICC values, with a maximal discrepancy of 0.01 (DSC-ICC) across all subfields. The pre-trained model, source code, and settings for the CAST toolbox are publicly available.

Dataset Information

Unveiling new disease, pathway, and gene associations via multi-scale neural network.

Publications

Unveiling new disease, pathway, and gene associations via multi-scale neural network.

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