GOWDL: gene ontology-driven wide and deep learning model for cell typing of scRNA-seq data
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PROVIDER: S-EPMC10530315 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:The development of single cell transcriptome sequencing has allowed researchers the possibility to dig inside the role of the individual cell types in a plethora of disease scenarios. It also expands to the whole transcriptome what before was only possible for a few tenths of antibodies in cell population analysis. More importantly, it allows resolving the permanent question of whether the changes observed in a particular bulk experiment are a consequence of changes in cell type proportions or an aberrant behavior of a particular cell type. However, single cell experiments are still complex to perform and expensive to sequence making bulk RNA-Seq experiments yet more common. scRNA-Seq data is proving highly relevant information for the characterization of the immune cell repertoire in different diseases ranging from cancer to atherosclerosis. In particular, as scRNA-Seq becomes more widely used, new types of immune cell populations emerge and their role in the genesis and evolution of the disease opens new avenues for personalized immune therapies. Immunotherapy have already proven successful in a variety of tumors such as breast, colon and melanoma and its value in other types of disease is being currently explored. From a statistical perspective, single-cell data are particularly interesting due to its high dimensionality, overcoming the limitations of the "skinny matrix" that traditional bulk RNA-Seq experiments yield. With the technological advances that enable sequencing hundreds of thousands of cells, scRNA-Seq data have become especially suitable for the application of Machine Learning algorithms such as Deep Learning (DL). We present here a DL based method to enumerate and quantify the immune infiltration in colorectal and breast cancer bulk RNA-Seq samples starting from scRNA-Seq. Our method makes use of a Deep Neural Network (DNN) model that allows quantification not only of lymphocytes as a general population but also of specific CD8+, CD4Tmem, CD4Th and CD4Tregs subpopulations, as well as B-cells and Stromal content. Moreover, the signatures are built from scRNA-Seq data from the tumor, preserving the specific characteristics of the tumor microenvironment as opposite to other approaches in which cells were isolated from blood. Our method was applied to synthetic bulk RNA-Seq and to samples from the TCGA project yielding very accurate results in terms of quantification and survival prediction.
| S-EPMC6824295 | biostudies-literature
Project description:Large single-cell RNA datasets have contributed to unprecedented biological insight. Often, these take the form of cell atlases and serve as a reference for automating cell labeling of newly sequenced samples. Yet, classification algorithms have lacked the capacity to accurately annotate cells, particularly in complex datasets. Here we present SIMS (Scalable, Interpretable Machine Learning for Single-Cell), an end-to-end data-efficient machine learning pipeline for discrete classification of single-cell data that can be applied to new datasets with minimal coding. We benchmarked SIMS against common single-cell label transfer tools and demonstrated that it performs as well or better than state of the art algorithms. We then use SIMS to classify cells in one of the most complex tissues: the brain. We show that SIMS classifies cells of the adult cerebral cortex and hippocampus at a remarkably higher accuracy than state-of-the-art single cell classifiers. This accuracy is maintained in trans-sample label transfers of the adult human cerebral cortex. We then apply SIMS to classify cells in the developing brain and demonstrate a high level of accuracy at predicting neuronal subtypes, even in periods of fate refinement. Finally, we apply SIMS to single cell datasets of cortical organoids to predict cell identities in previously unclassified cells and to uncover genetic variations in the developmental trajectories of organoids derived from different pluripotent stem cell lines. Altogether, we show that SIMS is a versatile and robust tool for cell-type classification from single-cell datasets.
| S-EPMC10002667 | biostudies-literature
Project description:Annotation of cell-types is a critical step in the analysis of single-cell RNA sequencing (scRNA-seq) data that allows the study of heterogeneity across multiple cell populations. Currently, this is most commonly done using unsupervised clustering algorithms, which project single-cell expression data into a lower dimensional space and then cluster cells based on their distances from each other. However, as these methods do not use reference datasets, they can only achieve a rough classification of cell-types, and it is difficult to improve the recognition accuracy further. To effectively solve this issue, we propose a novel supervised annotation method, scDeepInsight. The scDeepInsight method is capable of performing manifold assignments. It is competent in executing data integration through batch normalization, performing supervised training on the reference dataset, doing outlier detection and annotating cell-types on query datasets. Moreover, it can help identify active genes or marker genes related to cell-types. The training of the scDeepInsight model is performed in a unique way. Tabular scRNA-seq data are first converted to corresponding images through the DeepInsight methodology. DeepInsight can create a trainable image transformer to convert non-image RNA data to images by comprehensively comparing interrelationships among multiple genes. Subsequently, the converted images are fed into convolutional neural networks such as EfficientNet-b3. This enables automatic feature extraction to identify the cell-types of scRNA-seq samples. We benchmarked scDeepInsight with six other mainstream cell annotation methods. The average accuracy rate of scDeepInsight reached 87.5%, which is more than 7% higher compared with the state-of-the-art methods.
| S-EPMC10516353 | biostudies-literature
Project description:High dimensionality and noise have limited the new biological insights that can be discovered in scRNA-seq data. While dimensionality reduction tools have been developed to extract biological signals from the data, they often require manual determination of signal dimension, introducing user bias. Furthermore, a common data preprocessing method, log normalization, can unintentionally distort signals in the data. Here, we develop scLENS, a dimensionality reduction tool that circumvents the long-standing issues of signal distortion and manual input. Specifically, we identify the primary cause of signal distortion during log normalization and effectively address it by uniformizing cell vector lengths with L2 normalization. Furthermore, we utilize random matrix theory-based noise filtering and a signal robustness test to enable data-driven determination of the threshold for signal dimensions. Our method outperforms 11 widely used dimensionality reduction tools and performs particularly well for challenging scRNA-seq datasets with high sparsity and variability. To facilitate the use of scLENS, we provide a user-friendly package that automates accurate signal detection of scRNA-seq data without manual time-consuming tuning.
| S-EPMC11519519 | biostudies-literature
Project description:Single cell RNA sequencing (scRNA-seq) enables researchers to characterize transcriptomic profiles at the single-cell resolution with increasingly high throughput. Clustering is a crucial step in single cell analysis. Clustering analysis of transcriptome profiled by scRNA-seq can reveal the heterogeneity and diversity of cells. However, single cell study still remains great challenges due to its high noise and dimension. Subspace clustering aims at discovering the intrinsic structure of data in unsupervised fashion. In this paper, we propose a deep sparse subspace clustering method scDSSC combining noise reduction and dimensionality reduction for scRNA-seq data, which simultaneously learns feature representation and clustering via explicit modelling of scRNA-seq data generation. Experiments on a variety of scRNA-seq datasets from thousands to tens of thousands of cells have shown that scDSSC can significantly improve clustering performance and facilitate the interpretability of clustering and downstream analysis. Compared to some popular scRNA-deq analysis methods, scDSSC outperformed state-of-the-art methods under various clustering performance metrics.
| S-EPMC9810169 | biostudies-literature
Project description:Since its selection as the method of the year in 2013, single-cell technologies have become mature enough to provide answers to complex research questions. With the growth of single-cell profiling technologies, there has also been a significant increase in data collected from single-cell profilings, resulting in computational challenges to process these massive and complicated datasets. To address these challenges, deep learning (DL) is positioned as a competitive alternative for single-cell analyses besides the traditional machine learning approaches. Here, we survey a total of 25 DL algorithms and their applicability for a specific step in the single cell RNA-seq processing pipeline. Specifically, we establish a unified mathematical representation of variational autoencoder, autoencoder, generative adversarial network and supervised DL models, compare the training strategies and loss functions for these models, and relate the loss functions of these models to specific objectives of the data processing step. Such a presentation will allow readers to choose suitable algorithms for their particular objective at each step in the pipeline. We envision that this survey will serve as an important information portal for learning the application of DL for scRNA-seq analysis and inspire innovative uses of DL to address a broader range of new challenges in emerging multi-omics and spatial single-cell sequencing.
| S-EPMC8769926 | biostudies-literature
Project description:MotivationSingle-cell RNA sequencing (scRNA-seq) has become a valuable tool for studying cellular heterogeneity. However, the analysis of scRNA-seq data is challenging because of inherent noise and technical variability. Existing methods often struggle to simultaneously explore heterogeneity across cells, handle dropout events, and account for batch effects. These drawbacks call for a robust and comprehensive method that can address these challenges and provide accurate insights into heterogeneity at the single-cell level.ResultsIn this study, we introduce scVIC, an algorithm designed to account for variational inference, while simultaneously handling biological heterogeneity and batch effects at the single-cell level. scVIC explicitly models both biological heterogeneity and technical variability to learn cellular heterogeneity in a manner free from dropout events and the bias of batch effects. By leveraging variational inference, we provide a robust framework for inferring the parameters of scVIC. To test the performance of scVIC, we employed both simulated and biological scRNA-seq datasets, either including, or not, batch effects. scVIC was found to outperform other approaches because of its superior clustering ability and circumvention of the batch effects problem.Availability and implementationThe code of scVIC and replication for this study are available at https://github.com/HiBearME/scVIC/tree/v1.0.
| S-EPMC11256938 | biostudies-literature
Project description:By providing high-resolution of cell-to-cell variation in gene expression, single-cell RNA sequencing (scRNA-seq) offers insights into cell heterogeneity, differentiating dynamics, and disease mechanisms. However, challenges such as low capture rates and dropout events can introduce noise in data analysis. Here, we propose a deep neural generative framework, the dynamic batching adversarial autoencoder (DB-AAE), which excels at denoising scRNA-seq datasets. DB-AAE directly captures optimal features from input data and enhances feature preservation, including cell type-specific gene expression patterns. Comprehensive evaluation on simulated and real datasets demonstrates that DB-AAE outperforms other methods in denoising accuracy and biological signal preservation. It also improves the accuracy of other algorithms in establishing pseudo-time inference. This study highlights DB-AAE's effectiveness and potential as a valuable tool for enhancing the quality and reliability of downstream analyses in scRNA-seq research.
| S-EPMC10867661 | biostudies-literature
Project description:Recent advances of single-cell RNA sequencing (scRNA-seq) technologies have led to extensive study of cellular heterogeneity and cell-to-cell variation. However, the high frequency of dropout events and noise in scRNA-seq data confounds the accuracy of the downstream analysis, i.e. clustering analysis, whose accuracy depends heavily on the selected feature genes. Here, by deriving an entropy decomposition formula, we propose a feature selection method, i.e. an intrinsic entropy (IE) model, to identify the informative genes for accurately clustering analysis. Specifically, by eliminating the 'noisy' fluctuation or extrinsic entropy (EE), we extract the IE of each gene from the total entropy (TE), i.e. TE = IE + EE. We show that the IE of each gene actually reflects the regulatory fluctuation of this gene in a cellular process, and thus high-IE genes provide rich information on cell type or state analysis. To validate the performance of the high-IE genes, we conduct computational analysis on both simulated datasets and real single-cell datasets by comparing with other representative methods. The results show that our IE model is not only broadly applicable and robust for different clustering and classification methods, but also sensitive for novel cell types. Our results also demonstrate that the intrinsic entropy/fluctuation of a gene serves as information rather than noise in contrast to its total entropy/fluctuation.
| S-EPMC9175189 | biostudies-literature
Project description:BackgroundDyslexia is a neurological disorder that affects an individual's language processing abilities. Early care and intervention can help dyslexic individuals succeed academically and socially. Recent developments in deep learning (DL) approaches motivate researchers to build dyslexia detection models (DDMs). DL approaches facilitate the integration of multi-modality data. However, there are few multi-modality-based DDMs.MethodsIn this study, the authors built a DL-based DDM using multi-modality data. A squeeze and excitation (SE) integrated MobileNet V3 model, self-attention mechanisms (SA) based EfficientNet B7 model, and early stopping and SA-based Bi-directional long short-term memory (Bi-LSTM) models were developed to extract features from magnetic resonance imaging (MRI), functional MRI, and electroencephalography (EEG) data. In addition, the authors fine-tuned the LightGBM model using the Hyperband optimization technique to detect dyslexia using the extracted features. Three datasets containing FMRI, MRI, and EEG data were used to evaluate the performance of the proposed DDM.ResultsThe findings supported the significance of the proposed DDM in detecting dyslexia with limited computational resources. The proposed model outperformed the existing DDMs by producing an optimal accuracy of 98.9%, 98.6%, and 98.8% for the FMRI, MRI, and EEG datasets, respectively. Healthcare centers and educational institutions can benefit from the proposed model to identify dyslexia in the initial stages. The interpretability of the proposed model can be improved by integrating vision transformers-based feature extraction.
| S-EPMC11232624 | biostudies-literature