Flexible comparison of batch correction methods for single-cell RNA-seq using BatchBench.
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ABSTRACT:
SUBMITTER: Chazarra-Gil R
PROVIDER: S-EPMC8053088 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dimensionality reduction and visualization play an important role in biological data analysis, such as data interpretation of single-cell RNA sequences (scRNA-seq). It is desired to have a visualization method that can not only be applicable to various application scenarios, including cell clustering and trajectory inference, but also satisfy a variety of technical requirements, especially the ability to preserve inherent structure of data and handle with batch effects. However, no existing methods can accommodate these requirements in a unified framework. In this paper, we propose a general visualization method, deep visualization (DV), that possesses the ability to preserve inherent structure of data and handle batch effects and is applicable to a variety of datasets from different application domains and dataset scales. The method embeds a given dataset into a 2- or 3-dimensional visualization space, with either a Euclidean or hyperbolic metric depending on a specified task type with type static (at a time point) or dynamic (at a sequence of time points) scRNA-seq data, respectively. Specifically, DV learns a structure graph to describe the relationships between data samples, transforms the data into visualization space while preserving the geometric structure of the data and correcting batch effects in an end-to-end manner. The experimental results on nine datasets in complex tissue from human patients or animal development demonstrate the competitiveness of DV in discovering complex cellular relations, uncovering temporal trajectories, and addressing complex batch factors. We also provide a preliminary attempt to pre-train a DV model for visualization of new incoming data.
| S-EPMC10073100 | biostudies-literature
Project description:Despite their widespread applications, single-cell RNA-sequencing (scRNA-seq) experiments are still plagued by batch effects and dropout events. Although the completely randomized experimental design has frequently been advocated to control for batch effects, it is rarely implemented in real applications due to time and budget constraints. Here, we mathematically prove that under two more flexible and realistic experimental designs-the reference panel and the chain-type designs-true biological variability can also be separated from batch effects. We develop Batch effects correction with Unknown Subtypes for scRNA-seq data (BUSseq), which is an interpretable Bayesian hierarchical model that closely follows the data-generating mechanism of scRNA-seq experiments. BUSseq can simultaneously correct batch effects, cluster cell types, impute missing data caused by dropout events, and detect differentially expressed genes without requiring a preliminary normalization step. We demonstrate that BUSseq outperforms existing methods with simulated and real data.
| S-EPMC7330047 | biostudies-literature
Project description:BACKGROUND:Large-scale single-cell transcriptomic datasets generated using different technologies contain batch-specific systematic variations that present a challenge to batch-effect removal and data integration. With continued growth expected in scRNA-seq data, achieving effective batch integration with available computational resources is crucial. Here, we perform an in-depth benchmark study on available batch correction methods to determine the most suitable method for batch-effect removal. RESULTS:We compare 14 methods in terms of computational runtime, the ability to handle large datasets, and batch-effect correction efficacy while preserving cell type purity. Five scenarios are designed for the study: identical cell types with different technologies, non-identical cell types, multiple batches, big data, and simulated data. Performance is evaluated using four benchmarking metrics including kBET, LISI, ASW, and ARI. We also investigate the use of batch-corrected data to study differential gene expression. CONCLUSION:Based on our results, Harmony, LIGER, and Seurat 3 are the recommended methods for batch integration. Due to its significantly shorter runtime, Harmony is recommended as the first method to try, with the other methods as viable alternatives.
| S-EPMC6964114 | biostudies-literature
Project description:Batch effect correction has been recognized to be indispensable when integrating single-cell RNA sequencing (scRNA-seq) data from multiple batches. State-of-the-art methods ignore single-cell cluster label information, but such information can improve the effectiveness of batch effect correction, particularly under realistic scenarios where biological differences are not orthogonal to batch effects. To address this issue, we propose SMNN for batch effect correction of scRNA-seq data via supervised mutual nearest neighbor detection. Our extensive evaluations in simulated and real datasets show that SMNN provides improved merging within the corresponding cell types across batches, leading to reduced differentiation across batches over MNN, Seurat v3 and LIGER. Furthermore, SMNN retains more cell-type-specific features, partially manifested by differentially expressed genes identified between cell types after SMNN correction being biologically more relevant, with precision improving by up to 841.0%.
| S-EPMC8324985 | biostudies-literature
Project description:Batch effect correction is an essential step in the integrative analysis of multiple single-cell RNA-sequencing (scRNA-seq) data. One state-of-the-art strategy for batch effect correction is via unsupervised or supervised detection of mutual nearest neighbors (MNNs). However, both types of methods only detect MNNs across batches of uncorrected data, where the large batch effects may affect the MNN search. To address this issue, we presented a batch effect correction approach via iterative supervised MNN (iSMNN) refinement across data after correction. Our benchmarking on both simulation and real datasets showed the advantages of the iterative refinement of MNNs on the performance of correction. Compared to popular alternative methods, our iSMNN is able to better mix the cells of the same cell type across batches. In addition, iSMNN can also facilitate the identification of differentially expressed genes (DEGs) that are relevant to the biological function of certain cell types. These results indicated that iSMNN will be a valuable method for integrating multiple scRNA-seq datasets that can facilitate biological and medical studies at single-cell level.
| S-EPMC8579191 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology performed at the level of an individual cell, which can have a potential to understand cellular heterogeneity. However, scRNA-seq data are high-dimensional, noisy, and sparse data. Dimension reduction is an important step in downstream analysis of scRNA-seq. Therefore, several dimension reduction methods have been developed. We developed a strategy to evaluate the stability, accuracy, and computing cost of 10 dimensionality reduction methods using 30 simulation datasets and five real datasets. Additionally, we investigated the sensitivity of all the methods to hyperparameter tuning and gave users appropriate suggestions. We found that t-distributed stochastic neighbor embedding (t-SNE) yielded the best overall performance with the highest accuracy and computing cost. Meanwhile, uniform manifold approximation and projection (UMAP) exhibited the highest stability, as well as moderate accuracy and the second highest computing cost. UMAP well preserves the original cohesion and separation of cell populations. In addition, it is worth noting that users need to set the hyperparameters according to the specific situation before using the dimensionality reduction methods based on non-linear model and neural network.
| S-EPMC8021860 | biostudies-literature
Project description:The power of single-cell RNA sequencing (scRNA-seq) in detecting cell heterogeneity or developmental process is becoming more and more evident every day. The granularity of this knowledge is further propelled when combining two batches of scRNA-seq into a single large dataset. This strategy is however hampered by technical differences between these batches. Typically, these batch effects are resolved by matching similar cells across the different batches. Current approaches, however, do not take into account that we can constrain this matching further as cells can also be matched on their cell type identity. We use an auto-encoder to embed two batches in the same space such that cells are matched. To accomplish this, we use a loss function that preserves: (1) cell-cell distances within each of the two batches, as well as (2) cell-cell distances between two batches when the cells are of the same cell-type. The cell-type guidance is unsupervised, i.e., a cell-type is defined as a cluster in the original batch. We evaluated the performance of our cluster-guided batch alignment (CBA) using pancreas and mouse cell atlas datasets, against six state-of-the-art single cell alignment methods: Seurat v3, BBKNN, Scanorama, Harmony, LIGER, and BERMUDA. Compared to other approaches, CBA preserves the cluster separation in the original datasets while still being able to align the two datasets. We confirm that this separation is biologically meaningful by identifying relevant differential expression of genes for these preserved clusters.
| S-EPMC8076908 | biostudies-literature
Project description:Integration of single-cell RNA-sequencing (scRNA-seq) datasets has become a standard part of the analysis, with conditional variational autoencoders (cVAE) being among the most popular approaches. Increasingly, researchers are asking to map cells across challenging cases such as cross-organs, species, or organoids and primary tissue, as well as different scRNA-seq protocols, including single-cell and single-nuclei. Current computational methods struggle to harmonize datasets with such substantial differences, driven by technical or biological variation. Here, we propose to address these challenges for the popular cVAE-based approaches by introducing and comparing a series of regularization constraints. The two commonly used strategies for increasing batch correction in cVAEs, that is Kullback-Leibler divergence (KL) regularization strength tuning and adversarial learning, suffer from substantial loss of biological information. Therefore, we adapt, implement, and assess alternative regularization strategies for cVAEs and investigate how they improve batch effect removal or better preserve biological variation, enabling us to propose an optimal cVAE-based integration strategy for complex systems. We show that using a VampPrior instead of the commonly used Gaussian prior not only improves the preservation of biological variation but also unexpectedly batch correction. Moreover, we show that our implementation of cycle-consistency loss leads to significantly better biological preservation than adversarial learning implemented in the previously proposed GLUE model. Additionally, we do not recommend relying only on the KL regularization strength tuning for increasing batch correction, as it removes both biological and batch information without discriminating between the two. Based on our findings, we propose a new model that combines VampPrior and cycle-consistency loss. We show that using it for datasets with substantial batch effects improves downstream interpretation of cell states and biological conditions. To ease the use of the newly proposed model, we make it available in the scvi-tools package as an external model named sysVI. Moreover, in the future, these regularization techniques could be added to other established cVAE-based models to improve the integration of datasets with substantial batch effects.
| S-EPMC10635119 | biostudies-literature
Project description:With the development of single-cell RNA sequencing (scRNA-seq) technology, analysts need to integrate hundreds of thousands of cells with multiple experimental batches. It is becoming increasingly difficult for users to select the best integration methods to remove batch effects. Here, we compared the advantages and limitations of four commonly used Scanpy-based batch-correction methods using two representative and large-scale scRNA-seq datasets. We quantitatively evaluated batch-correction performance and efficiency. Furthermore, we discussed the performance differences among the evaluated methods at the algorithm level.
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Project description:We have assessed the performance of seven normalization methods for single cell RNA-seq using data generated from dilution of RNA samples. Our analyses showed that methods considering spike-in External RNA Control Consortium (ERCC) RNA molecules significantly outperformed those not considering ERCCs. This work provides a guidance of selecting normalization methods to remove technical noise in single cell RNA-seq data.
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