DeepG4: A deep learning approach to predict cell-type specific active G-quadruplex regions.
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ABSTRACT:
SUBMITTER: Rocher V
PROVIDER: S-EPMC8384162 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundA number of deep learning models have been developed to predict epigenetic features such as chromatin accessibility from DNA sequence. Model evaluations commonly report performance genome-wide; however, cis regulatory elements (CREs), which play critical roles in gene regulation, make up only a small fraction of the genome. Furthermore, cell type-specific CREs contain a large proportion of complex disease heritability.ResultsWe evaluate genomic deep learning models in chromatin accessibility regions with varying degrees of cell type specificity. We assess two modeling directions in the field: general purpose models trained across thousands of outputs (cell types and epigenetic marks) and models tailored to specific tissues and tasks. We find that the accuracy of genomic deep learning models, including two state-of-the-art general purpose models-Enformer and Sei-varies across the genome and is reduced in cell type-specific accessible regions. Using accessibility models trained on cell types from specific tissues, we find that increasing model capacity to learn cell type-specific regulatory syntax-through single-task learning or high capacity multi-task models-can improve performance in cell type-specific accessible regions. We also observe that improving reference sequence predictions does not consistently improve variant effect predictions, indicating that novel strategies are needed to improve performance on variants.ConclusionsOur results provide a new perspective on the performance of genomic deep learning models, showing that performance varies across the genome and is particularly reduced in cell type-specific accessible regions. We also identify strategies to maximize performance in cell type-specific accessible regions.
| S-EPMC11293111 | biostudies-literature
Project description:The blood-brain barrier plays a crucial role in regulating the passage of 98% of the compounds that enter the central nervous system (CNS). Compounds with high permeability must be identified to enable the synthesis of brain medications for the treatment of various brain diseases, such as Parkinson's, Alzheimer's, and brain tumors. Throughout the years, several models have been developed to solve this problem and have achieved acceptable accuracy scores in predicting compounds that penetrate the blood-brain barrier. However, predicting compounds with "low" permeability has been a challenging task. In this study, we present a deep learning (DL) classification model to predict blood-brain barrier permeability. The proposed model addresses the fundamental issues presented in former models: high dimensionality, class imbalances, and low specificity scores. We address these issues to enhance the high-dimensional, imbalanced dataset before developing the classification model: the imbalanced dataset is addressed using oversampling techniques and the high dimensionality using a non-linear dimensionality reduction technique known as kernel principal component analysis (KPCA). This technique transforms the high-dimensional dataset into a low-dimensional Euclidean space while retaining invaluable information. For the classification task, we developed an enhanced feed-forward deep learning model and a convolutional neural network model. In terms of specificity scores (i.e., predicting compounds with low permeability), the results obtained by the enhanced feed-forward deep learning model outperformed those obtained by other models in the literature that were developed using the same technique. In addition, the proposed convolutional neural network model surpassed models used in other studies in multiple accuracy measures, including overall accuracy and specificity. The proposed approach solves the problem inevitably faced with obtaining low specificity resulting in high false positive rate.
| S-EPMC8205267 | biostudies-literature
Project description:ObjectiveTo develop and evaluate deep learning (DL) risk assessment models for predicting pain progression in subjects with or at risk of knee osteoarthritis (OA).Materials and methodsThe incidence and progression cohorts of the Osteoarthritis Initiative, a multi-center longitudinal study involving 9348 knees in 4674 subjects with or at risk of knee OA that began in 2004 and is ongoing, were used to conduct this retrospective analysis. A subset of knees without and with pain progression (defined as a 9-point or greater increase in pain score between baseline and two or more follow-up time points over the first 48 months) was randomly stratified into training (4200 knees with a mean age of 61.0 years and 60% female) and hold-out testing (500 knees with a mean age of 60.8 years and 60% female) datasets. A DL model was developed to predict pain progression using baseline knee radiographs. An artificial neural network was used to develop a traditional risk assessment model to predict pain progression using demographic, clinical, and radiographic risk factors. A combined model was developed to combine demographic, clinical, and radiographic risk factors with DL analysis of baseline knee radiographs. Area under the curve (AUC) analysis was performed using the hold-out testing dataset to evaluate model performance.ResultsThe traditional model had an AUC of 0.692 (66.9% sensitivity and 64.1% specificity). The DL model had an AUC of 0.770 (76.7% sensitivity and 70.5% specificity), which was significantly higher (p < 0.001) than the traditional model. The combined model had an AUC of 0.807 (72.3% sensitivity and 80.9% specificity), which was significantly higher (p < 0.05) than the traditional and DL models.ConclusionsDL models using baseline knee radiographs had higher diagnostic performance for predicting pain progression than traditional models using demographic, clinical, and radiographic risk factors.
| S-EPMC9232386 | biostudies-literature
Project description:Interpretation of noncoding genomic variants is one of the most important challenges in human genetics. Machine learning methods have emerged recently as a powerful tool to solve this problem. State-of-the-art approaches allow prediction of transcriptional and epigenetic effects caused by noncoding mutations. However, these approaches require specific experimental data for training and cannot generalize across cell types where required features were not experimentally measured. We show here that available epigenetic characteristics of human cell types are extremely sparse, limiting those approaches that rely on specific epigenetic input. We propose a new neural network architecture, DeepCT, which can learn complex interconnections of epigenetic features and infer unmeasured data from any available input. Furthermore, we show that DeepCT can learn cell type-specific properties, build biologically meaningful vector representations of cell types, and utilize these representations to generate cell type-specific predictions of the effects of noncoding variations in the human genome.
| S-EPMC10041527 | biostudies-literature
Project description:Phosphorylation, which is mediated by protein kinases and opposed by protein phosphatases, is an important post-translational modification that regulates many cellular processes, including cellular metabolism, cell migration, and cell division. Due to its essential role in cellular physiology, a great deal of attention has been devoted to identifying sites of phosphorylation on cellular proteins and understanding how modification of these sites affects their cellular functions. This has led to the development of several computational methods designed to predict sites of phosphorylation based on a protein's primary amino acid sequence. In contrast, much less attention has been paid to dephosphorylation and its role in regulating the phosphorylation status of proteins inside cells. Indeed, to date, dephosphorylation site prediction tools have been restricted to a few tyrosine phosphatases. To fill this knowledge gap, we have employed a transfer learning strategy to develop a deep learning-based model to predict sites that are likely to be dephosphorylated. Based on independent test results, our model, which we termed DTL-DephosSite, achieved efficiency scores for phosphoserine/phosphothreonine residues of 84%, 84% and 0.68 with respect to sensitivity (SN), specificity (SP) and Matthew's correlation coefficient (MCC). Similarly, DTL-DephosSite exhibited efficiency scores of 75%, 88% and 0.64 for phosphotyrosine residues with respect to SN, SP, and MCC.
| S-EPMC8264445 | biostudies-literature
Project description:Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and is a useful measure in drug design. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. Performing such analyses to cover the entire chemical space of small molecules requires intense computational power. Recent developments using deep learning have enabled us to make sense of massive amounts of complex data sets where the ability of the model to "learn" intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated convolutional neural networks to find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies toward a diverse set of ligands without the need of a docked pose or complex as user input. The models were trained and validated using a stringent methodology for feature extraction. Our model performs better in comparison to some existing methods used widely and is suitable for predictions on high-resolution protein crystal (⩽2.5 Å) and nonpeptide ligand as individual inputs. Our approach to network construction and training on protein-ligand data set prepared in-house has yielded significant insights. We have also tested DEELIG on few COVID-19 main protease-inhibitor complexes relevant to the current public health scenario. DEELIG-based predictions can be incorporated in existing databases including RSCB PDB, PDBMoad, and PDBbind in filling missing binding affinity data for protein-ligand complexes.
| S-EPMC8274096 | biostudies-literature
Project description:Computational methods to predict Z-DNA regions are in high demand to understand the functional role of Z-DNA. The previous state-of-the-art method Z-Hunt is based on statistical mechanical and energy considerations about B- to Z-DNA transition using sequence information. Z-DNA CHiP-seq experiment results showed little overlap with Z-Hunt predictions implying that sequence information only is not sufficient to explain emergence of Z-DNA at different genomic locations. Adding epigenetic and other functional genomic mark-ups to DNA sequence level can help revealing the functional Z-DNA sites. Here we take advantage of the deep learning approach that can analyze and extract information from large volumes of molecular biology data. We developed a machine learning approach DeepZ that aggregates information from genome-wide maps of epigenetic markers, transcription factor and RNA polymerase binding sites, and chromosome accessibility maps. With the developed model we not only verify the experimental Z-DNA predictions, but also generate the whole-genome annotation, introducing new possible Z-DNA regions, which have not yet been found in experiments and can be of interest to the researchers from various fields.
| S-EPMC7644757 | biostudies-literature
Project description:BackgroundFunctional gene networks (FGNs) capture functional relationships among genes that vary across tissues and cell types. Construction of cell-type-specific FGNs enables the understanding of cell-type-specific functional gene relationships and insights into genetic mechanisms of human diseases in disease-relevant cell types. However, most existing FGNs were developed without consideration of specific cell types within tissues.ResultsIn this study, we created a multimodal deep learning model (MDLCN) to predict cell-type-specific FGNs in the human brain by integrating single-nuclei gene expression data with global protein interaction networks. We systematically evaluated the prediction performance of the MDLCN and showed its superior performance compared to two baseline models (boosting tree and convolutional neural network). Based on the predicted cell-type-specific FGNs, we observed that cell-type marker genes had a higher level of hubness than non-marker genes in their corresponding cell type. Furthermore, we showed that risk genes underlying autism and Alzheimer's disease were more strongly connected in disease-relevant cell types, supporting the cellular context of predicted cell-type-specific FGNs.ConclusionsOur study proposes a powerful deep learning approach (MDLCN) to predict FGNs underlying a diverse set of cell types in human brain. The MDLCN model enhances prediction accuracy of cell-type-specific FGNs compared to single modality convolutional neural network (CNN) and boosting tree models, as shown by higher areas under both receiver operating characteristic (ROC) and precision-recall curves for different levels of independent test datasets. The predicted FGNs also show evidence for the cellular context and distinct topological features (i.e. higher hubness and topological score) of cell-type marker genes. Moreover, we observed stronger modularity among disease-associated risk genes in FGNs of disease-relevant cell types. For example, the strength of connectivity among autism risk genes was stronger in neurons, but risk genes underlying Alzheimer's disease were more connected in microglia.
| S-EPMC9926713 | biostudies-literature
Project description:Deep venous thrombosis (DVT) is associated with significant morbidity, mortality, and increased healthcare costs. Standard scoring systems for DVT risk stratification often provide insufficient stratification of hospitalized patients and are unable to accurately predict which inpatients are most likely to present with DVT. There is a continued need for tools which can predict DVT in hospitalized patients. We performed a retrospective study on a database collected from a large academic hospital, comprised of 99,237 total general ward or ICU patients, 2,378 of whom experienced a DVT during their hospital stay. Gradient boosted machine learning algorithms were developed to predict a patient's risk of developing DVT at 12- and 24-hour windows prior to onset. The primary outcome of interest was diagnosis of in-hospital DVT. The machine learning predictors obtained AUROCs of 0.83 and 0.85 for DVT risk prediction on hospitalized patients at 12- and 24-hour windows, respectively. At both 12 and 24 hours before DVT onset, the most important features for prediction of DVT were cancer history, VTE history, and internal normalized ratio (INR). Improved risk stratification may prevent unnecessary invasive testing in patients for whom DVT cannot be ruled out using existing methods. Improved risk stratification may also allow for more targeted use of prophylactic anticoagulants, as well as earlier diagnosis and treatment, preventing the development of pulmonary emboli and other sequelae of DVT.
| S-EPMC7907939 | biostudies-literature
Project description:We developed a deep learning architecture based on Inception V3 to predict visual field using optical coherence tomography (OCT) imaging and evaluated its performance. Two OCT images, macular ganglion cell-inner plexiform layer (mGCIPL) and peripapillary retinal nerve fibre layer (pRNFL) thicknesses, were acquired and combined. A convolutional neural network architecture was constructed to predict visual field using this combined OCT image. The root mean square error (RMSE) between the actual and predicted visual fields was calculated to evaluate the performance. Globally (the entire visual field area), the RMSE for all patients was 4.79 ± 2.56 dB, with 3.27 dB and 5.27 dB for the normal and glaucoma groups, respectively. The RMSE of the macular region (4.40 dB) was higher than that of the peripheral region (4.29 dB) for all subjects. In normal subjects, the RMSE of the macular region (2.45 dB) was significantly lower than that of the peripheral region (3.11 dB), whereas in glaucoma subjects, the RMSE was higher (5.62 dB versus 5.03 dB, respectively). The deep learning method effectively predicted the visual field 24-2 using the combined OCT image. This method may help clinicians determine visual fields, particularly for patients who are unable to undergo a physical visual field exam.
| S-EPMC7337305 | biostudies-literature