Benchmarking single-cell cross-omics imputation methods for surface protein expression

Abstract Background Recent advances in single-cell multimodal omics sequencing have facilitated the simultaneous profiling of transcriptomes and surface proteomes within individual cells, offering insights into cellular functions and heterogeneity. However, the high costs and technical complexity of...

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Main Authors: Chen-Yang Li, Yong-Jia Hong, Bo Li, Xiao-Fei Zhang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Genome Biology
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Online Access:https://doi.org/10.1186/s13059-025-03514-9
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author Chen-Yang Li
Yong-Jia Hong
Bo Li
Xiao-Fei Zhang
author_facet Chen-Yang Li
Yong-Jia Hong
Bo Li
Xiao-Fei Zhang
author_sort Chen-Yang Li
collection DOAJ
description Abstract Background Recent advances in single-cell multimodal omics sequencing have facilitated the simultaneous profiling of transcriptomes and surface proteomes within individual cells, offering insights into cellular functions and heterogeneity. However, the high costs and technical complexity of protocols like CITE-seq and REAP-seq constrain large-scale dataset generation. To overcome this limitation, surface protein data imputation methods have emerged to predict protein abundances from scRNA-seq data. Results We present a comprehensive benchmark of twelve state-of-the-art imputation methods across eleven datasets and six scenarios. Our analysis evaluates the methods’ accuracy, sensitivity to training data size, robustness across experiments, and usability in terms of running time, memory usage, popularity, and user-friendliness. With benchmark experiments in diverse scenarios and a comprehensive evaluation framework of the results, our study offers valuable insights into the performance and applicability of surface protein data imputation methods in single-cell omics research. Conclusions Based on our results, Seurat v4 (PCA) and Seurat v3 (PCA) demonstrate exceptional performance, offering promising avenues for further research in single-cell omics.
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spelling doaj-art-445971c9ac834e38a9d30d76f0ccd0fc2025-08-20T02:59:57ZengBMCGenome Biology1474-760X2025-03-0126113010.1186/s13059-025-03514-9Benchmarking single-cell cross-omics imputation methods for surface protein expressionChen-Yang Li0Yong-Jia Hong1Bo Li2Xiao-Fei Zhang3School of Mathematics and Statistics, and Hubei Key Lab–Math. Sci., Central China Normal UniversitySchool of Mathematics and Statistics, and Hubei Key Lab–Math. Sci., Central China Normal UniversitySchool of Mathematics and Statistics, and Hubei Key Lab–Math. Sci., Central China Normal UniversitySchool of Mathematics and Statistics, and Hubei Key Lab–Math. Sci., Central China Normal UniversityAbstract Background Recent advances in single-cell multimodal omics sequencing have facilitated the simultaneous profiling of transcriptomes and surface proteomes within individual cells, offering insights into cellular functions and heterogeneity. However, the high costs and technical complexity of protocols like CITE-seq and REAP-seq constrain large-scale dataset generation. To overcome this limitation, surface protein data imputation methods have emerged to predict protein abundances from scRNA-seq data. Results We present a comprehensive benchmark of twelve state-of-the-art imputation methods across eleven datasets and six scenarios. Our analysis evaluates the methods’ accuracy, sensitivity to training data size, robustness across experiments, and usability in terms of running time, memory usage, popularity, and user-friendliness. With benchmark experiments in diverse scenarios and a comprehensive evaluation framework of the results, our study offers valuable insights into the performance and applicability of surface protein data imputation methods in single-cell omics research. Conclusions Based on our results, Seurat v4 (PCA) and Seurat v3 (PCA) demonstrate exceptional performance, offering promising avenues for further research in single-cell omics.https://doi.org/10.1186/s13059-025-03514-9Single-cell multimodal omicsSingle-cell RNA-seqSurface protein expressionCross-omics imputationBenchmark
spellingShingle Chen-Yang Li
Yong-Jia Hong
Bo Li
Xiao-Fei Zhang
Benchmarking single-cell cross-omics imputation methods for surface protein expression
Genome Biology
Single-cell multimodal omics
Single-cell RNA-seq
Surface protein expression
Cross-omics imputation
Benchmark
title Benchmarking single-cell cross-omics imputation methods for surface protein expression
title_full Benchmarking single-cell cross-omics imputation methods for surface protein expression
title_fullStr Benchmarking single-cell cross-omics imputation methods for surface protein expression
title_full_unstemmed Benchmarking single-cell cross-omics imputation methods for surface protein expression
title_short Benchmarking single-cell cross-omics imputation methods for surface protein expression
title_sort benchmarking single cell cross omics imputation methods for surface protein expression
topic Single-cell multimodal omics
Single-cell RNA-seq
Surface protein expression
Cross-omics imputation
Benchmark
url https://doi.org/10.1186/s13059-025-03514-9
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