scholarly journals Unified AI framework to uncover deep interrelationships between gene expression and Alzheimer’s disease neuropathologies

2020 ◽  
Author(s):  
Nicasia Beebe-Wang ◽  
Safiye Celik ◽  
Ethan Weinberger ◽  
Pascal Sturmfels ◽  
Philip L. De Jager ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Deep Neural Networks ◽  
Joint Analysis ◽  
Linear Relationships ◽  
Non Linear ◽  
Consistent Manner ◽  
Complex Relationships ◽  
Expression Program ◽  
Linear Interactions

ABSTRACTDeep neural networks offer a promising approach for capturing complex, non-linear relationships among variables. Because they require immense sample sizes, their potential has yet to be fully tapped for understanding complex relationships between gene expression and human phenotypes. Encouragingly, a growing number of diseases are being studied through consortium efforts. Here we introduce a new analysis framework, namely MD-AD (Multi-task Deep learning for Alzheimer’s Disease neuropathology), which leverages an unexpected synergy between deep neural networks and multi-cohort settings. In these settings, true joint analysis can be stymied using conventional statistical methods, which (1) require “harmonized” phenotypes (i.e., measured in a highly consistent manner) and (2) tend to capture cohort-level variations, obscuring the subtler true disease signals. Instead, MD-AD incorporates multiple related phenotypes sparsely measured across cohorts, and learns complex, non-linear interactions between genes and phenotypes not discovered using conventional expression data analysis methods (e.g., component analysis and module detection), enabling the model to capture subtler signals than cohort-level variations. Applied to the largest available collection of brain samples (N=1,758), we demonstrate that MD-AD learns a truly generalizable relationship between gene expression program and AD-related neuropathology. The learned program generalizes in several important ways, including recapitulation of the disease progress in animal models and across tissue types, and we show that such generalizability is not achieved by previous statistical paradigms. Its ability to identify genes with high non-linear relevance to neuropathology enabled us to identify a sex-specific relationship between neuropathology and immune response across microglia, providing a nuanced context for association between inflammatory genes and AD.

scholarly journals Unified AI framework to uncover deep interrelationships between gene expression and Alzheimer’s disease neuropathologies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicasia Beebe-Wang ◽  
Safiye Celik ◽  
Ethan Weinberger ◽  
Pascal Sturmfels ◽  
Philip L. De Jager ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Neural Networks ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Deep Neural Networks ◽  
Linear Models ◽  
Joint Analysis ◽  
Analysis Framework ◽  
Complex Relationships

AbstractDeep neural networks (DNNs) capture complex relationships among variables, however, because they require copious samples, their potential has yet to be fully tapped for understanding relationships between gene expression and human phenotypes. Here we introduce an analysis framework, namely MD-AD (Multi-task Deep learning for Alzheimer’s Disease neuropathology), which leverages an unexpected synergy between DNNs and multi-cohort settings. In these settings, true joint analysis can be stymied using conventional statistical methods, which require “harmonized” phenotypes and tend to capture cohort-level variations, obscuring subtler true disease signals. Instead, MD-AD incorporates related phenotypes sparsely measured across cohorts, and learns interactions between genes and phenotypes not discovered using linear models, identifying subtler signals than cohort-level variations which can be uniquely recapitulated in animal models and across tissues. We show that MD-AD exploits sex-specific relationships between microglial immune response and neuropathology, providing a nuanced context for the association between inflammatory genes and Alzheimer’s Disease.

Analysis of Non-Linear Activation Functions for Classification Tasks Using Convolutional Neural Networks

2019 ◽  
Vol 12 (3) ◽  
pp. 156-161 ◽  
Author(s):  
Aman Dureja ◽  
Payal Pahwa
Keyword(s):  
Neural Networks ◽  
Deep Neural Networks ◽  
Activation Function ◽  
Primary Objective ◽  
Experimental Comparison ◽  
Activation Functions ◽  
Practical Applications ◽  
Network Activation ◽  
Non Linear ◽  
Hidden Layer

Background: In making the deep neural network, activation functions play an important role. But the choice of activation functions also affects the network in term of optimization and to retrieve the better results. Several activation functions have been introduced in machine learning for many practical applications. But which activation function should use at hidden layer of deep neural networks was not identified. Objective: The primary objective of this analysis was to describe which activation function must be used at hidden layers for deep neural networks to solve complex non-linear problems. Methods: The configuration for this comparative model was used by using the datasets of 2 classes (Cat/Dog). The number of Convolutional layer used in this network was 3 and the pooling layer was also introduced after each layer of CNN layer. The total of the dataset was divided into the two parts. The first 8000 images were mainly used for training the network and the next 2000 images were used for testing the network. Results: The experimental comparison was done by analyzing the network by taking different activation functions on each layer of CNN network. The validation error and accuracy on Cat/Dog dataset were analyzed using activation functions (ReLU, Tanh, Selu, PRelu, Elu) at number of hidden layers. Overall the Relu gave best performance with the validation loss at 25th Epoch 0.3912 and validation accuracy at 25th Epoch 0.8320. Conclusion: It is found that a CNN model with ReLU hidden layers (3 hidden layers here) gives best results and improve overall performance better in term of accuracy and speed. These advantages of ReLU in CNN at number of hidden layers are helpful to effectively and fast retrieval of images from the databases.

High-throughput single-cell RNA-seq data imputation and characterization with surrogate-assisted automated deep learning

2021 ◽  
Author(s):  
Xiangtao Li ◽  
Shaochuan Li ◽  
Lei Huang ◽  
Shixiong Zhang ◽  
Ka-chun Wong
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Single Cell ◽  
Deep Neural Networks ◽  
Expression Profiles ◽  
Marker Gene ◽  
Gene Expression Profiles ◽  
Underlying Mechanisms ◽  
Cell Data ◽  
Gene Expression Levels

Abstract Single-cell RNA sequencing (scRNA-seq) technologies have been heavily developed to probe gene expression profiles at single-cell resolution. Deep imputation methods have been proposed to address the related computational challenges (e.g. the gene sparsity in single-cell data). In particular, the neural architectures of those deep imputation models have been proven to be critical for performance. However, deep imputation architectures are difficult to design and tune for those without rich knowledge of deep neural networks and scRNA-seq. Therefore, Surrogate-assisted Evolutionary Deep Imputation Model (SEDIM) is proposed to automatically design the architectures of deep neural networks for imputing gene expression levels in scRNA-seq data without any manual tuning. Moreover, the proposed SEDIM constructs an offline surrogate model, which can accelerate the computational efficiency of the architectural search. Comprehensive studies show that SEDIM significantly improves the imputation and clustering performance compared with other benchmark methods. In addition, we also extensively explore the performance of SEDIM in other contexts and platforms including mass cytometry and metabolic profiling in a comprehensive manner. Marker gene detection, gene ontology enrichment and pathological analysis are conducted to provide novel insights into cell-type identification and the underlying mechanisms. The source code is available at https://github.com/li-shaochuan/SEDIM.

scholarly journals Cell Identity Codes: Understanding Cell Identity from Gene Expression Profiles using Deep Neural Networks

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Farzad Abdolhosseini ◽  
Behrooz Azarkhalili ◽  
Abbas Maazallahi ◽  
Aryan Kamal ◽  
Seyed Abolfazl Motahari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Deep Neural Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Identity

scholarly journals MOLI: multi-omics late integration with deep neural networks for drug response prediction

2019 ◽  
Vol 35 (14) ◽  
pp. i501-i509 ◽  
Author(s):  
Hossein Sharifi-Noghabi ◽  
Olga Zolotareva ◽  
Colin C Collins ◽  
Martin Ester
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Prediction Accuracy ◽  
Drug Response ◽  
Deep Neural Networks ◽  
Response Prediction ◽  
Supplementary Information ◽  
Precision Oncology

Abstract Motivation Historically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance. Results We propose MOLI, a multi-omics late integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding sub-networks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each other and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology. Availability and implementation https://github.com/hosseinshn/MOLI. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Perspectives for analyzing non-linear photo ionization spectra with deep neural networks trained with synthetic Hamilton matrices

2020 ◽  
Author(s):  
Sajal Giri ◽  
Lazaro Alonso ◽  
Ulf Saalmann ◽  
Jan M. Michael Rost
Keyword(s):  
Neural Networks ◽  
Deep Neural Networks ◽  
Electron Spectra ◽  
Non Linear ◽  
Photo Ionization

We have constructed deep neural networks, which can map fluctuating photo-electron spectra obtained from noisy pulses to spectra from noise-free pulses. The network is trained on spectra from noisy pulses...

scholarly journals MOLI: Multi-Omics Late Integration with deep neural networks for drug response prediction

2019 ◽  
Author(s):  
Hossein Sharifi-Noghabi ◽  
Olga Zolotareva ◽  
Colin C. Collins ◽  
Martin Ester
Keyword(s):  
Gene Expression ◽  
Neural Networks ◽  
Prediction Accuracy ◽  
Drug Response ◽  
Deep Neural Networks ◽  
Response Prediction ◽  
Precision Oncology ◽  
Early Integration

AbstractMotivationHistorically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance.ResultsWe propose MOLI, a Multi-Omics Late Integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration, and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding subnetworks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI’s performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI’s high predictive power suggests it may have utility in precision oncology.Availability of the implemented codeshttps://github.com/hosseinshn/[email protected] and [email protected]

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