scholarly journals Modeling positional effects of regulatory sequences with spline transformations increases prediction accuracy of deep neural networks

2017 ◽  
Author(s):  
Žiga Avsec ◽  
Mohammadamin Barekatain ◽  
Jun Cheng ◽  
Julien Gagneur
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Prediction Accuracy ◽  
Deep Neural Networks ◽  
Rna Binding ◽  
Piecewise Linear ◽  
Regulatory Sequences ◽  
Link Type

AbstractMotivationRegulatory sequences are not solely defined by their nucleic acid sequence but also by their relative distances to genomic landmarks such as transcription start site, exon boundaries, or polyadenylation site. Deep learning has become the approach of choice for modeling regulatory sequences because of its strength to learn complex sequence features. However, modeling relative distances to genomic landmarks in deep neural networks has not been addressed.ResultsHere we developed spline transformation, a neural network module based on splines to flexibly and robustly model distances. Modeling distances to various genomic landmarks with spline transformations significantly increased state-of-the-art prediction accuracy of in vivo RNA-binding protein binding sites for 114 out of 123 proteins. We also developed a deep neural network for human splice branchpoint based on spline transformations that outperformed the current best, already distance-based, machine learning model. Compared to piecewise linear transformation, as obtained by composition of rectified linear units, spline transformation yields higher prediction accuracy as well as faster and more robust training. As spline transformation can be applied to further quantities beyond distances, such as methylation or conservation, we foresee it as a versatile component in the genomics deep learning toolbox.AvailabilitySpline transformation is implemented as a Keras layer in the CONCISE python package: https://github.com/gagneurlab/concise. Analysis code is available at goo.gl/[email protected]; [email protected]

scholarly journals Multi-resBind: a residual network-based multi-label classifier for in vivo RNA binding prediction and preference visualization

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shitao Zhao ◽  
Michiaki Hamada
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Binding Sites ◽  
Prediction Accuracy ◽  
Large Scale ◽  
Rna Binding ◽  
Binding Prediction ◽  
Binding Preference ◽  
The Impact

Abstract Background Protein-RNA interactions play key roles in many processes regulating gene expression. To understand the underlying binding preference, ultraviolet cross-linking and immunoprecipitation (CLIP)-based methods have been used to identify the binding sites for hundreds of RNA-binding proteins (RBPs) in vivo. Using these large-scale experimental data to infer RNA binding preference and predict missing binding sites has become a great challenge. Some existing deep-learning models have demonstrated high prediction accuracy for individual RBPs. However, it remains difficult to avoid significant bias due to the experimental protocol. The DeepRiPe method was recently developed to solve this problem via introducing multi-task or multi-label learning into this field. However, this method has not reached an ideal level of prediction power due to the weak neural network architecture. Results Compared to the DeepRiPe approach, our Multi-resBind method demonstrated substantial improvements using the same large-scale PAR-CLIP dataset with respect to an increase in the area under the receiver operating characteristic curve and average precision. We conducted extensive experiments to evaluate the impact of various types of input data on the final prediction accuracy. The same approach was used to evaluate the effect of loss functions. Finally, a modified integrated gradient was employed to generate attribution maps. The patterns disentangled from relative contributions according to context offer biological insights into the underlying mechanism of protein-RNA interactions. Conclusions Here, we propose Multi-resBind as a new multi-label deep-learning approach to infer protein-RNA binding preferences and predict novel interactions. The results clearly demonstrate that Multi-resBind is a promising tool to predict unknown binding sites in vivo and gain biology insights into why the neural network makes a given prediction.

scholarly journals Semiotic Aggregation in Deep Learning

Entropy ◽  
2020 ◽  
Vol 22 (12) ◽  
pp. 1365
Author(s):  
Bogdan Muşat ◽  
Răzvan Andonie
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Decision Model ◽  
Deep Neural Networks ◽  
Neural Model ◽  
Network Layers ◽  
Saliency Maps ◽  
Spatial Entropy ◽  
Insight Into

Convolutional neural networks utilize a hierarchy of neural network layers. The statistical aspects of information concentration in successive layers can bring an insight into the feature abstraction process. We analyze the saliency maps of these layers from the perspective of semiotics, also known as the study of signs and sign-using behavior. In computational semiotics, this aggregation operation (known as superization) is accompanied by a decrease of spatial entropy: signs are aggregated into supersign. Using spatial entropy, we compute the information content of the saliency maps and study the superization processes which take place between successive layers of the network. In our experiments, we visualize the superization process and show how the obtained knowledge can be used to explain the neural decision model. In addition, we attempt to optimize the architecture of the neural model employing a semiotic greedy technique. To the extent of our knowledge, this is the first application of computational semiotics in the analysis and interpretation of deep neural networks.

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.

Identification of Thoracic Diseases by Exploiting Deep Neural Networks (Preprint)

2020 ◽  
Author(s):  
Albahli Saleh ◽  
Ali Alkhalifah
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Convolutional Neural Network ◽  
Deep Neural Networks ◽  
Medical Image Analysis ◽  
Medical Community ◽  
Learning Models ◽  
X Ray ◽  
Chest Disease

BACKGROUND To diagnose cardiothoracic diseases, a chest x-ray (CXR) is examined by a radiologist. As more people get affected, doctors are becoming scarce especially in developing countries. However, with the advent of image processing tools, the task of diagnosing these cardiothoracic diseases has seen great progress. A lot of researchers have put in work to see how the problems associated with medical images can be mitigated by using neural networks. OBJECTIVE Previous works used state-of-the-art techniques and got effective results with one or two cardiothoracic diseases but could lead to misclassification. In our work, we adopted GANs to synthesize the chest radiograph (CXR) to augment the training set on multiple cardiothoracic diseases to efficiently diagnose the chest diseases in different classes as shown in Figure 1. In this regard, our major contributions are classifying various cardiothoracic diseases to detect a specific chest disease based on CXR, use the advantage of GANs to overcome the shortages of small training datasets, address the problem of imbalanced data; and implementing optimal deep neural network architecture with different hyper-parameters to improve the model with the best accuracy. METHODS For this research, we are not building a model from scratch due to computational restraints as they require very high-end computers. Rather, we use a Convolutional Neural Network (CNN) as a class of deep neural networks to propose a generative adversarial network (GAN) -based model to generate synthetic data for training the data as the amount of the data is limited. We will use pre-trained models which are models that were trained on a large benchmark dataset to solve a problem similar to the one we want to solve. For example, the ResNet-152 model we used was initially trained on the ImageNet dataset. RESULTS After successful training and validation of the models we developed, ResNet-152 with image augmentation proved to be the best model for the automatic detection of cardiothoracic disease. However, one of the main problems associated with radiographic deep learning projects and research is the scarcity and unavailability of enough datasets which is a key component of all deep learning models as they require a lot of data for training. This is the reason why some of our models had image augmentation to increase the number of images without duplication. As more data are collected in the field of chest radiology, the models could be retrained to improve the accuracies of the models as deep learning models improve with more data. CONCLUSIONS This research employs the advantages of computer vision and medical image analysis to develop an automated model that has the clinical potential for early detection of the disease. Using deep learning models, the research aims to evaluate the effectiveness and accuracy of different convolutional neural network models in the automatic diagnosis of cardiothoracic diseases from x-ray images compared to diagnosis by experts in the medical community.

scholarly journals Mimicry Embedding Facilitates Advanced Neural Network Training for Image-Based Pathogen Detection

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Artur Yakimovich ◽  
Moona Huttunen ◽  
Jerzy Samolej ◽  
Barbara Clough ◽  
Nagisa Yoshida ◽  
...  
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Deep Neural Networks ◽  
Network Evolution ◽  
Great Promise ◽  
Data Sets ◽  
Imaging Data ◽  
Data Set ◽  
Novel Strategy

ABSTRACT The use of deep neural networks (DNNs) for analysis of complex biomedical images shows great promise but is hampered by a lack of large verified data sets for rapid network evolution. Here, we present a novel strategy, termed “mimicry embedding,” for rapid application of neural network architecture-based analysis of pathogen imaging data sets. Embedding of a novel host-pathogen data set, such that it mimics a verified data set, enables efficient deep learning using high expressive capacity architectures and seamless architecture switching. We applied this strategy across various microbiological phenotypes, from superresolved viruses to in vitro and in vivo parasitic infections. We demonstrate that mimicry embedding enables efficient and accurate analysis of two- and three-dimensional microscopy data sets. The results suggest that transfer learning from pretrained network data may be a powerful general strategy for analysis of heterogeneous pathogen fluorescence imaging data sets. IMPORTANCE In biology, the use of deep neural networks (DNNs) for analysis of pathogen infection is hampered by a lack of large verified data sets needed for rapid network evolution. Artificial neural networks detect handwritten digits with high precision thanks to large data sets, such as MNIST, that allow nearly unlimited training. Here, we developed a novel strategy we call mimicry embedding, which allows artificial intelligence (AI)-based analysis of variable pathogen-host data sets. We show that deep learning can be used to detect and classify single pathogens based on small differences.

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]

scholarly journals An optical neural network using less than 1 photon per multiplication

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Tianyu Wang ◽  
Shi-Yuan Ma ◽  
Logan G. Wright ◽  
Tatsuhiro Onodera ◽  
Brian C. Richard ◽  
...  
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Deep Neural Networks ◽  
Fundamental Principle ◽  
Energy Costs ◽  
Network Architectures ◽  
Optical Neural Networks ◽  
Optical Neural Network ◽  
Handwritten Digit

AbstractDeep learning has become a widespread tool in both science and industry. However, continued progress is hampered by the rapid growth in energy costs of ever-larger deep neural networks. Optical neural networks provide a potential means to solve the energy-cost problem faced by deep learning. Here, we experimentally demonstrate an optical neural network based on optical dot products that achieves 99% accuracy on handwritten-digit classification using ~3.1 detected photons per weight multiplication and ~90% accuracy using ~0.66 photons (~2.5 × 10−19 J of optical energy) per weight multiplication. The fundamental principle enabling our sub-photon-per-multiplication demonstration—noise reduction from the accumulation of scalar multiplications in dot-product sums—is applicable to many different optical-neural-network architectures. Our work shows that optical neural networks can achieve accurate results using extremely low optical energies.

scholarly journals Exploring deep neural networks via layer-peeled model: Minority collapse in imbalanced training

2021 ◽  
Vol 118 (43) ◽  
pp. e2103091118
Author(s):  
Cong Fang ◽  
Hangfeng He ◽  
Qi Long ◽  
Weijie J. Su
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Deep Neural Networks ◽  
Model Minority ◽  
Tight Frame ◽  
Learning Models ◽  
The Neural Network ◽  
Long Time ◽  
Topmost Layer

In this paper, we introduce the Layer-Peeled Model, a nonconvex, yet analytically tractable, optimization program, in a quest to better understand deep neural networks that are trained for a sufficiently long time. As the name suggests, this model is derived by isolating the topmost layer from the remainder of the neural network, followed by imposing certain constraints separately on the two parts of the network. We demonstrate that the Layer-Peeled Model, albeit simple, inherits many characteristics of well-trained neural networks, thereby offering an effective tool for explaining and predicting common empirical patterns of deep-learning training. First, when working on class-balanced datasets, we prove that any solution to this model forms a simplex equiangular tight frame, which, in part, explains the recently discovered phenomenon of neural collapse [V. Papyan, X. Y. Han, D. L. Donoho, Proc. Natl. Acad. Sci. U.S.A. 117, 24652–24663 (2020)]. More importantly, when moving to the imbalanced case, our analysis of the Layer-Peeled Model reveals a hitherto-unknown phenomenon that we term Minority Collapse, which fundamentally limits the performance of deep-learning models on the minority classes. In addition, we use the Layer-Peeled Model to gain insights into how to mitigate Minority Collapse. Interestingly, this phenomenon is first predicted by the Layer-Peeled Model before being confirmed by our computational experiments.

scholarly journals Tri-net for Semi-Supervised Deep Learning

2018 ◽  
Author(s):  
Dong-Dong Chen ◽  
Wei Wang ◽  
Wei Gao ◽  
Zhi-Hua Zhou
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Deep Learning ◽  
Error Rate ◽  
Deep Neural Network ◽  
Deep Neural Networks ◽  
State Of The Art ◽  
Fine Tuning ◽  
Learning Methods ◽  
Model Initialization

Deep neural networks have witnessed great successes in various real applications, but it requires a large number of labeled data for training. In this paper, we propose tri-net, a deep neural network which is able to use massive unlabeled data to help learning with limited labeled data. We consider model initialization, diversity augmentation and pseudo-label editing simultaneously. In our work, we utilize output smearing to initialize modules, use fine-tuning on labeled data to augment diversity and eliminate unstable pseudo-labels to alleviate the influence of suspicious pseudo-labeled data. Experiments show that our method achieves the best performance in comparison with state-of-the-art semi-supervised deep learning methods. In particular, it achieves 8.30% error rate on CIFAR-10 by using only 4000 labeled examples.

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