Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution
Abstract The variation of transcriptome size across cell types significantly impacts single-cell RNA sequencing (scRNA-seq) data normalization and bulk RNA-seq cellular deconvolution, yet this intrinsic feature is often overlooked. Here we introduce ReDeconv, a computational algorithm that incorpora...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56623-1 |
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| _version_ | 1832571556063084544 |
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| author | Songjian Lu Jiyuan Yang Lei Yan Jingjing Liu Judy Jiaru Wang Rhea Jain Jiyang Yu |
| author_facet | Songjian Lu Jiyuan Yang Lei Yan Jingjing Liu Judy Jiaru Wang Rhea Jain Jiyang Yu |
| author_sort | Songjian Lu |
| collection | DOAJ |
| description | Abstract The variation of transcriptome size across cell types significantly impacts single-cell RNA sequencing (scRNA-seq) data normalization and bulk RNA-seq cellular deconvolution, yet this intrinsic feature is often overlooked. Here we introduce ReDeconv, a computational algorithm that incorporates transcriptome size into scRNA-seq normalization and bulk deconvolution. ReDeconv introduces a scRNA-seq normalization approach, Count based on Linearized Transcriptome Size (CLTS), which corrects differential expressed genes typically misidentified by standard count per 10 K normalization, as confirmed by orthogonal validations. By maintaining transcriptome size variation, CLTS-normalized scRNA-seq enhances the accuracy of bulk deconvolution. Additionally, ReDeconv mitigates gene length effects and models expression variances, thereby improving deconvolution outcomes, particularly for rare cell types. Evaluated with both synthetic and real datasets, ReDeconv surpasses existing methods in precision. ReDeconv alters the practice and provides a new standard for scRNA-seq analyses and bulk deconvolution. The software packages and a user-friendly web portal are available. |
| format | Article |
| id | doaj-art-f520ecec142447a7948b7f7ca6c6d94d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f520ecec142447a7948b7f7ca6c6d94d2025-02-02T12:31:36ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56623-1Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolutionSongjian Lu0Jiyuan Yang1Lei Yan2Jingjing Liu3Judy Jiaru Wang4Rhea Jain5Jiyang Yu6Department of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalDepartment of Computational Biology, St. Jude Children’s Research HospitalAbstract The variation of transcriptome size across cell types significantly impacts single-cell RNA sequencing (scRNA-seq) data normalization and bulk RNA-seq cellular deconvolution, yet this intrinsic feature is often overlooked. Here we introduce ReDeconv, a computational algorithm that incorporates transcriptome size into scRNA-seq normalization and bulk deconvolution. ReDeconv introduces a scRNA-seq normalization approach, Count based on Linearized Transcriptome Size (CLTS), which corrects differential expressed genes typically misidentified by standard count per 10 K normalization, as confirmed by orthogonal validations. By maintaining transcriptome size variation, CLTS-normalized scRNA-seq enhances the accuracy of bulk deconvolution. Additionally, ReDeconv mitigates gene length effects and models expression variances, thereby improving deconvolution outcomes, particularly for rare cell types. Evaluated with both synthetic and real datasets, ReDeconv surpasses existing methods in precision. ReDeconv alters the practice and provides a new standard for scRNA-seq analyses and bulk deconvolution. The software packages and a user-friendly web portal are available.https://doi.org/10.1038/s41467-025-56623-1 |
| spellingShingle | Songjian Lu Jiyuan Yang Lei Yan Jingjing Liu Judy Jiaru Wang Rhea Jain Jiyang Yu Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution Nature Communications |
| title | Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution |
| title_full | Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution |
| title_fullStr | Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution |
| title_full_unstemmed | Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution |
| title_short | Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution |
| title_sort | transcriptome size matters for single cell rna seq normalization and bulk deconvolution |
| url | https://doi.org/10.1038/s41467-025-56623-1 |
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