scholarly journals CRISPRL and: Interpretable large-scale inference of DNA repair landscape based on a spectral approach

2020 ◽  
Vol 36 (Supplement_1) ◽  
pp. i560-i568 ◽  
Author(s):  
Amirali Aghazadeh ◽  
Orhan Ocal ◽  
Kannan Ramchandran

Abstract Summary We propose a new spectral framework for reliable training, scalable inference and interpretable explanation of the DNA repair outcome following a Cas9 cutting. Our framework, dubbed CRISPRL and, relies on an unexploited observation about the nature of the repair process: the landscape of the DNA repair is highly sparse in the (Walsh–Hadamard) spectral domain. This observation enables our framework to address key shortcomings that limit the interpretability and scaling of current deep-learning-based DNA repair models. In particular, CRISPRL and reduces the time to compute the full DNA repair landscape from a striking 5230 years to 1 week and the sampling complexity from 1012 to 3 million guide RNAs with only a small loss in accuracy (R2R2 ∼ 0.9). Our proposed framework is based on a divide-and-conquer strategy that uses a fast peeling algorithm to learn the DNA repair models. CRISPRL and captures lower-degree features around the cut site, which enrich for short insertions and deletions as well as higher-degree microhomology patterns that enrich for longer deletions. Availability and implementation The CRISPRL and software is publicly available at https://github.com/UCBASiCS/CRISPRLand.

2021 ◽  
Author(s):  
Jingyi Wei ◽  
Peter Lotfy ◽  
Kian Faizi ◽  
Hugo Kitano ◽  
Patrick D. Hsu ◽  
...  

AbstractTranscriptome engineering requires flexible RNA-targeting technologies that can perturb mammalian transcripts in a robust and scalable manner. CRISPR systems that natively target RNA molecules, such as Cas13 enzymes, are enabling rapid progress in the investigation of RNA biology and advancement of RNA therapeutics. Here, we sought to develop a Cas13 platform for high-throughput phenotypic screening and elucidate the design principles underpinning its RNA targeting efficiency. We employed the RfxCas13d (CasRx) system in a positive selection screen by tiling 55 known essential genes with single nucleotide resolution. Leveraging this dataset of over 127,000 guide RNAs, we systematically compared a series of linear regression and machine learning algorithms to train a convolutional neural network (CNN) model that is able to robustly predict guide RNA performance based on guide sequence alone. We further incorporated secondary features including secondary structure, free energy, target site position, and target isoform percent. To evaluate model performance, we conducted orthogonal screens via cell surface protein knockdown. The final CNN model is able to predict highly effective guide RNAs (gRNAs) within each transcript with >90% accuracy in this independent test set. To provide user interpretability, we evaluate feature contributions using both integrated gradients and SHapley Additive exPlanations (SHAP). We identify a specific sequence motif at guide position 15-24 along with selected secondary features to be predictive of highly efficient guides. Taken together, we derive Cas13d guide design rules from large-scale screen data, release a guide design tool (http://RNAtargeting.org) to advance the RNA targeting toolbox, and describe a path for systematic development of deep learning models to predict CRISPR activity.


2020 ◽  
Author(s):  
Anusha Ampavathi ◽  
Vijaya Saradhi T

UNSTRUCTURED Big data and its approaches are generally helpful for healthcare and biomedical sectors for predicting the disease. For trivial symptoms, the difficulty is to meet the doctors at any time in the hospital. Thus, big data provides essential data regarding the diseases on the basis of the patient’s symptoms. For several medical organizations, disease prediction is important for making the best feasible health care decisions. Conversely, the conventional medical care model offers input as structured that requires more accurate and consistent prediction. This paper is planned to develop the multi-disease prediction using the improvised deep learning concept. Here, the different datasets pertain to “Diabetes, Hepatitis, lung cancer, liver tumor, heart disease, Parkinson’s disease, and Alzheimer’s disease”, from the benchmark UCI repository is gathered for conducting the experiment. The proposed model involves three phases (a) Data normalization (b) Weighted normalized feature extraction, and (c) prediction. Initially, the dataset is normalized in order to make the attribute's range at a certain level. Further, weighted feature extraction is performed, in which a weight function is multiplied with each attribute value for making large scale deviation. Here, the weight function is optimized using the combination of two meta-heuristic algorithms termed as Jaya Algorithm-based Multi-Verse Optimization algorithm (JA-MVO). The optimally extracted features are subjected to the hybrid deep learning algorithms like “Deep Belief Network (DBN) and Recurrent Neural Network (RNN)”. As a modification to hybrid deep learning architecture, the weight of both DBN and RNN is optimized using the same hybrid optimization algorithm. Further, the comparative evaluation of the proposed prediction over the existing models certifies its effectiveness through various performance measures.


2017 ◽  
Vol 14 (9) ◽  
pp. 1513-1517 ◽  
Author(s):  
Rodrigo F. Berriel ◽  
Andre Teixeira Lopes ◽  
Alberto F. de Souza ◽  
Thiago Oliveira-Santos
Keyword(s):  

Author(s):  
Mathieu Turgeon-Pelchat ◽  
Samuel Foucher ◽  
Yacine Bouroubi

2020 ◽  
pp. bjophthalmol-2020-317825
Author(s):  
Yonghao Li ◽  
Weibo Feng ◽  
Xiujuan Zhao ◽  
Bingqian Liu ◽  
Yan Zhang ◽  
...  

Background/aimsTo apply deep learning technology to develop an artificial intelligence (AI) system that can identify vision-threatening conditions in high myopia patients based on optical coherence tomography (OCT) macular images.MethodsIn this cross-sectional, prospective study, a total of 5505 qualified OCT macular images obtained from 1048 high myopia patients admitted to Zhongshan Ophthalmic Centre (ZOC) from 2012 to 2017 were selected for the development of the AI system. The independent test dataset included 412 images obtained from 91 high myopia patients recruited at ZOC from January 2019 to May 2019. We adopted the InceptionResnetV2 architecture to train four independent convolutional neural network (CNN) models to identify the following four vision-threatening conditions in high myopia: retinoschisis, macular hole, retinal detachment and pathological myopic choroidal neovascularisation. Focal Loss was used to address class imbalance, and optimal operating thresholds were determined according to the Youden Index.ResultsIn the independent test dataset, the areas under the receiver operating characteristic curves were high for all conditions (0.961 to 0.999). Our AI system achieved sensitivities equal to or even better than those of retina specialists as well as high specificities (greater than 90%). Moreover, our AI system provided a transparent and interpretable diagnosis with heatmaps.ConclusionsWe used OCT macular images for the development of CNN models to identify vision-threatening conditions in high myopia patients. Our models achieved reliable sensitivities and high specificities, comparable to those of retina specialists and may be applied for large-scale high myopia screening and patient follow-up.


2020 ◽  
Vol 31 (6) ◽  
pp. 681-689
Author(s):  
Jalal Mirakhorli ◽  
Hamidreza Amindavar ◽  
Mojgan Mirakhorli

AbstractFunctional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer’s disease.


2021 ◽  
Vol 13 (8) ◽  
pp. 1509
Author(s):  
Xikun Hu ◽  
Yifang Ban ◽  
Andrea Nascetti

Accurate burned area information is needed to assess the impacts of wildfires on people, communities, and natural ecosystems. Various burned area detection methods have been developed using satellite remote sensing measurements with wide coverage and frequent revisits. Our study aims to expound on the capability of deep learning (DL) models for automatically mapping burned areas from uni-temporal multispectral imagery. Specifically, several semantic segmentation network architectures, i.e., U-Net, HRNet, Fast-SCNN, and DeepLabv3+, and machine learning (ML) algorithms were applied to Sentinel-2 imagery and Landsat-8 imagery in three wildfire sites in two different local climate zones. The validation results show that the DL algorithms outperform the ML methods in two of the three cases with the compact burned scars, while ML methods seem to be more suitable for mapping dispersed burn in boreal forests. Using Sentinel-2 images, U-Net and HRNet exhibit comparatively identical performance with higher kappa (around 0.9) in one heterogeneous Mediterranean fire site in Greece; Fast-SCNN performs better than others with kappa over 0.79 in one compact boreal forest fire with various burn severity in Sweden. Furthermore, directly transferring the trained models to corresponding Landsat-8 data, HRNet dominates in the three test sites among DL models and can preserve the high accuracy. The results demonstrated that DL models can make full use of contextual information and capture spatial details in multiple scales from fire-sensitive spectral bands to map burned areas. Using only a post-fire image, the DL methods not only provide automatic, accurate, and bias-free large-scale mapping option with cross-sensor applicability, but also have potential to be used for onboard processing in the next Earth observation satellites.


Computers ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 82
Author(s):  
Ahmad O. Aseeri

Deep Learning-based methods have emerged to be one of the most effective and practical solutions in a wide range of medical problems, including the diagnosis of cardiac arrhythmias. A critical step to a precocious diagnosis in many heart dysfunctions diseases starts with the accurate detection and classification of cardiac arrhythmias, which can be achieved via electrocardiograms (ECGs). Motivated by the desire to enhance conventional clinical methods in diagnosing cardiac arrhythmias, we introduce an uncertainty-aware deep learning-based predictive model design for accurate large-scale classification of cardiac arrhythmias successfully trained and evaluated using three benchmark medical datasets. In addition, considering that the quantification of uncertainty estimates is vital for clinical decision-making, our method incorporates a probabilistic approach to capture the model’s uncertainty using a Bayesian-based approximation method without introducing additional parameters or significant changes to the network’s architecture. Although many arrhythmias classification solutions with various ECG feature engineering techniques have been reported in the literature, the introduced AI-based probabilistic-enabled method in this paper outperforms the results of existing methods in outstanding multiclass classification results that manifest F1 scores of 98.62% and 96.73% with (MIT-BIH) dataset of 20 annotations, and 99.23% and 96.94% with (INCART) dataset of eight annotations, and 97.25% and 96.73% with (BIDMC) dataset of six annotations, for the deep ensemble and probabilistic mode, respectively. We demonstrate our method’s high-performing and statistical reliability results in numerical experiments on the language modeling using the gating mechanism of Recurrent Neural Networks.


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