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Main Authors: Anaissi, Ali, Zandavi, Seid Miad, Huang, Weidong, Akram, Junaid, Suleiman, Basem, Braytee, Ali, Hua, Jie
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2601.00277
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author Anaissi, Ali
Zandavi, Seid Miad
Huang, Weidong
Akram, Junaid
Suleiman, Basem
Braytee, Ali
Hua, Jie
author_facet Anaissi, Ali
Zandavi, Seid Miad
Huang, Weidong
Akram, Junaid
Suleiman, Basem
Braytee, Ali
Hua, Jie
contents Single-cell data analysis has the potential to revolutionize personalized medicine by characterizing disease-associated molecular changes at the single-cell level. Advanced single-cell multimodal assays can now simultaneously measure various molecules (e.g., DNA, RNA, Protein) across hundreds of thousands of individual cells, providing a comprehensive molecular readout. A significant analytical challenge is integrating single-cell measurements across different modalities. Various methods have been developed to address this challenge, but there has been no systematic evaluation of these techniques with different preprocessing strategies. This study examines a general pipeline for single-cell data analysis, which includes normalization, data integration, and dimensionality reduction. The performance of different algorithm combinations often depends on the dataset sizes and characteristics. We evaluate six datasets across diverse modalities, tissues, and organisms using three metrics: Silhouette Coefficient Score, Adjusted Rand Index, and Calinski-Harabasz Index. Our experiments involve combinations of seven normalization methods, four dimensional reduction methods, and five integration methods. The results show that Seurat and Harmony excel in data integration, with Harmony being more time-efficient, especially for large datasets. UMAP is the most compatible dimensionality reduction method with the integration techniques, and the choice of normalization method varies depending on the integration method used.
format Preprint
id arxiv_https___arxiv_org_abs_2601_00277
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Benchmarking Preprocessing and Integration Methods in Single-Cell Genomics
Anaissi, Ali
Zandavi, Seid Miad
Huang, Weidong
Akram, Junaid
Suleiman, Basem
Braytee, Ali
Hua, Jie
Quantitative Methods
Artificial Intelligence
Single-cell data analysis has the potential to revolutionize personalized medicine by characterizing disease-associated molecular changes at the single-cell level. Advanced single-cell multimodal assays can now simultaneously measure various molecules (e.g., DNA, RNA, Protein) across hundreds of thousands of individual cells, providing a comprehensive molecular readout. A significant analytical challenge is integrating single-cell measurements across different modalities. Various methods have been developed to address this challenge, but there has been no systematic evaluation of these techniques with different preprocessing strategies. This study examines a general pipeline for single-cell data analysis, which includes normalization, data integration, and dimensionality reduction. The performance of different algorithm combinations often depends on the dataset sizes and characteristics. We evaluate six datasets across diverse modalities, tissues, and organisms using three metrics: Silhouette Coefficient Score, Adjusted Rand Index, and Calinski-Harabasz Index. Our experiments involve combinations of seven normalization methods, four dimensional reduction methods, and five integration methods. The results show that Seurat and Harmony excel in data integration, with Harmony being more time-efficient, especially for large datasets. UMAP is the most compatible dimensionality reduction method with the integration techniques, and the choice of normalization method varies depending on the integration method used.
title Benchmarking Preprocessing and Integration Methods in Single-Cell Genomics
topic Quantitative Methods
Artificial Intelligence
url https://arxiv.org/abs/2601.00277