Similar Datasets
Project description:Single-cell RNA sequencing (scRNA-seq) can characterize cell types and states through unsupervised clustering, but the ever increasing number of cells and batch effect impose computational challenges. We present DESC, an unsupervised deep embedding algorithm that clusters scRNA-seq data by iteratively optimizing a clustering objective function. Through iterative self-learning, DESC gradually removes batch effects, as long as technical differences across batches are smaller than true biological variations. As a soft clustering algorithm, cluster assignment probabilities from DESC are biologically interpretable and can reveal both discrete and pseudotemporal structure of cells. Comprehensive evaluations show that DESC offers a proper balance of clustering accuracy and stability, has a small footprint on memory, does not explicitly require batch information for batch effect removal, and can utilize GPU when available. As the scale of single-cell studies continues to grow, we believe DESC will offer a valuable tool for biomedical researchers to disentangle complex cellular heterogeneity.
| S-EPMC7214470 | biostudies-literature
Project description:Deep learning enables accurate clustering with batch effect removal in single-cell RNA-seq analysis
| PRJNA612534 | ENA
Project description:Recent developments of single-cell RNA-seq (scRNA-seq) technologies have led to enormous biological discoveries. As the scale of scRNA-seq studies increases, a major challenge in analysis is batch effects, which are inevitable in studies involving human tissues. Most existing methods remove batch effects in a low-dimensional embedding space. Although useful for clustering, batch effects are still present in the gene expression space, leaving downstream gene-level analysis susceptible to batch effects. Recent studies have shown that batch effect correction in the gene expression space is much harder than in the embedding space. Methods such as Seurat 3.0 rely on the mutual nearest neighbor (MNN) approach to remove batch effects in gene expression, but MNN can only analyze two batches at a time, and it becomes computationally infeasible when the number of batches is large. Here, we present CarDEC, a joint deep learning model that simultaneously clusters and denoises scRNA-seq data while correcting batch effects both in the embedding and the gene expression space. Comprehensive evaluations spanning different species and tissues showed that CarDEC outperforms Scanorama, DCA + Combat, scVI, and MNN. With CarDEC denoising, non-highly variable genes offer as much signal for clustering as the highly variable genes (HVGs), suggesting that CarDEC substantially boosted information content in scRNA-seq. We also showed that trajectory analysis using CarDEC's denoised and batch-corrected expression as input revealed marker genes and transcription factors that are otherwise obscured in the presence of batch effects. CarDEC is computationally fast, making it a desirable tool for large-scale scRNA-seq studies.
| S-EPMC8494213 | biostudies-literature
Project description:A question of fundamental biological significance is to what extent the expression of a subset of genes can be used to recover the full transcriptome, with important implications for biological discovery and clinical application. To address this challenge, we propose two novel deep learning methods, PMI and GAIN-GTEx, for gene expression imputation. In order to increase the applicability of our approach, we leverage data from GTEx v8, a reference resource that has generated a comprehensive collection of transcriptomes from a diverse set of human tissues. We show that our approaches compare favorably to several standard and state-of-the-art imputation methods in terms of predictive performance and runtime in two case studies and two imputation scenarios. In comparison conducted on the protein-coding genes, PMI attains the highest performance in inductive imputation whereas GAIN-GTEx outperforms the other methods in in-place imputation. Furthermore, our results indicate strong generalization on RNA-Seq data from 3 cancer types across varying levels of missingness. Our work can facilitate a cost-effective integration of large-scale RNA biorepositories into genomic studies of disease, with high applicability across diverse tissue types.
| S-EPMC8076954 | biostudies-literature
Project description:Annotating active sites in enzymes is crucial for advancing multiple fields including drug discovery, disease research, enzyme engineering, and synthetic biology. Despite the development of numerous automated annotation algorithms, a significant trade-off between speed and accuracy limits their large-scale practical applications. We introduce EasIFA, an enzyme active site annotation algorithm that fuses latent enzyme representations from the Protein Language Model and 3D structural encoder, and then aligns protein-level information with the knowledge of enzymatic reactions using a multi-modal cross-attention framework. EasIFA outperforms BLASTp with a 10-fold speed increase and improved recall, precision, f1 score, and MCC by 7.57%, 13.08%, 9.68%, and 0.1012, respectively. It also surpasses empirical-rule-based algorithm and other state-of-the-art deep learning annotation method based on PSSM features, achieving a speed increase ranging from 650 to 1400 times while enhancing annotation quality. This makes EasIFA a suitable replacement for conventional tools in both industrial and academic settings. EasIFA can also effectively transfer knowledge gained from coarsely annotated enzyme databases to smaller, high-precision datasets, highlighting its ability to model sparse and high-quality databases. Additionally, EasIFA shows potential as a catalytic site monitoring tool for designing enzymes with desired functions beyond their natural distribution.
| S-EPMC11347633 | biostudies-literature
Project description:Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, revealing 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests, and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (HR = 1.43 per SD; CI 1.32-1.54; P = 3.3·10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.
2021-01-30 | GSE165824 | GEO
Project description:Single-cell sequencing provides novel means to interpret the transcriptomic profiles of individual cells. To obtain in-depth analysis of single-cell sequencing, it requires effective computational methods to accurately predict single-cell clusters because single-cell sequencing techniques only provide the transcriptomic profiles of each cell. Although an accurate estimation of the cell-to-cell similarity is an essential first step to derive reliable single-cell clustering results, it is challenging to obtain the accurate similarity measurement because it highly depends on a selection of genes for similarity evaluations and the optimal set of genes for the accurate similarity estimation is typically unknown. Moreover, due to technical limitations, single-cell sequencing includes a larger number of artificial zeros, and the technical noise makes it difficult to develop effective single-cell clustering algorithms. Here, we describe a novel single-cell clustering algorithm that can accurately predict single-cell clusters in large-scale single-cell sequencing by effectively reducing the zero-inflated noise and accurately estimating the cell-to-cell similarities. First, we construct an ensemble similarity network based on different similarity estimates, and reduce the artificial noise using a random walk with restart framework. Finally, starting from a larger number small size but highly consistent clusters, we iteratively merge a pair of clusters with the maximum similarities until it reaches the predicted number of clusters. Extensive performance evaluation shows that the proposed single-cell clustering algorithm can yield the accurate single-cell clustering results and it can help deciphering the key messages underlying complex biological mechanisms.
| S-EPMC8623803 | biostudies-literature
Project description:Abstract: The recently developed droplet-based single cell transcriptome sequencing (scRNA-seq) technology makes it feasible to perform a population-scale scRNA-seq study, in which the transcriptome is measured for tens of thousands of single cells from multiple individuals. Despite the advances of many clustering methods, there are few tailored methods for population-scale scRNA-seq studies. Here, we develop a BAyesian Mixture Model for Single Cell sequencing (BAMM-SC) method to cluster scRNA-seq data from multiple individuals simultaneously. BAMM-SC takes raw count data as input and accounts for data heterogeneity and batch effect among multiple individuals in a unified Bayesian hierarchical model framework. Results from applications of BAMM-SC to in-house experimental scRNA-seq datasets using blood and lung cells from humans or mice demonstrate that BAMM-SC outperformed existing clustering methods with considerable improved clustering accuracy, particularly in the presence of heterogeneity among individuals. Data purpose: To evaluate the performance of BAMM-SC for clustering droplet-based scRNA-seq data in population-based study, we performed single cell RNA-seq on peripheral blood mononuclear cells (PBMC) isolated from whole blood obtained from 4 healthy donors, and on lung cells isolated from streptococcus pneumonia (SP) infected and naïve mice.
2019-03-09 | GSE128066 | GEO
Project description:STED microscopy is widely used to image subcellular structures with super-resolution. Here, we report that restoring STED images with deep learning can mitigate photobleaching and photodamage by reducing the pixel dwell time by one or two orders of magnitude. Our method allows for efficient and robust restoration of noisy 2D and 3D STED images with multiple targets and facilitates long-term imaging of mitochondrial dynamics.
| S-EPMC10300082 | biostudies-literature
Project description:In this work, we present a local intrinsic rule that we developed, dubbed IP, inspired by the Infomax rule. Like Infomax, this rule works by controlling the gain and bias of a neuron to regulate its rate of fire. We discuss the biological plausibility of the IP rule and compare it to batch normalisation. We demonstrate that the IP rule improves learning in deep networks, and provides networks with considerable robustness to increases in synaptic learning rates. We also sample the error gradients during learning and show that the IP rule substantially increases the size of the gradients over the course of learning. This suggests that the IP rule solves the vanishing gradient problem. Supplementary analysis is provided to derive the equilibrium solutions that the neuronal gain and bias converge to using our IP rule. An analysis demonstrates that the IP rule results in neuronal information potential similar to that of Infomax, when tested on a fixed input distribution. We also show that batch normalisation also improves information potential, suggesting that this may be a cause for the efficacy of batch normalisation-an open problem at the time of this writing.
| S-EPMC7511202 | biostudies-literature