SIDR: simultaneous isolation and parallel sequencing of genomic DNA and total RNA from single cells
Open accessAbstract
Simultaneous sequencing of the genome and transcriptome at the single-cell level is a powerful tool for characterizing genomic and transcriptomic variation and revealing correlative relationships. However, it remains technically challenging to analyze both the genome and transcriptome in the same cell. Here, we report a novel method for simultaneous isolation of genomic DNA and total RNA (SIDR) from single cells, achieving high recovery rates with minimal cross-contamination, as is crucial for accurate description and integration of the single-cell genome and transcriptome. For reliable and efficient separation of genomic DNA and total RNA from single cells, the method uses hypotonic lysis to preserve nuclear lamina integrity and subsequently captures the cell lysate using antibody-conjugated magnetic microbeads. Evaluating the performance of this method using real-time PCR demonstrated that it efficiently recovered genomic DNA and total RNA. Thorough data quality assessments showed that DNA and RNA simultaneously fractionated by the SIDR method were suitable for genome and transcriptome sequencing analysis at the single-cell level. The integration of single-cell genome and transcriptome sequencing by SIDR (SIDR-seq) showed that genetic alterations, such as copy-number and single-nucleotide variations, were more accurately captured by single-cell SIDR-seq compared with conventional single-cell RNA-seq, although copy-number variations positively correlated with the corresponding gene expression levels. These results suggest that SIDR-seq is potentially a powerful tool to reveal genetic heterogeneity and phenotypic information inferred from gene expression patterns at the single-cell level.
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Many genes display copy-number gene-dosage effects on transcriptional expression.
“Previous work in which DNA and RNA were assayed in the same cells has shown that many genes display copy-number gene-dosage effects on transcriptional expression28–30.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [30]
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Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution
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Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction
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Evaluating microglial phenotypes using single-cell technologies
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Single-Cell Sequencing in Cancer: Recent Applications to Immunogenomics and Multi-omics Tools
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Multimodal single-cell approaches shed light on T cell heterogeneity
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Coalescing single-cell genomes and transcriptomes to decode breast cancer progression
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Single-cell technologies and analyses in hematopoiesis and hematological malignancies
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Advances in single‐cell sequencing and its application to musculoskeletal system research
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Tn5 DNA Transposase in Multi-Omics Research
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Single‐Cell and Spatial Omics: Methods and Applications
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Analyzing the functional effects of DNA variants with gene editing
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Single Cell RNA-Sequencing for the Study of Atherosclerosis
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Advancing Stem Cell Research through Multimodal Single-Cell AnalysisPreprint
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Single-cell epigenomics and proteomics methods integrated in multiomics
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Transcriptome analysis reveals phenanthrene degradation strategy of Pseudomonas stutzeri LH-42
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Single-Cell Molecular Barcoding to Decode Multimodal Information Defining Cell States
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Decoding Human Biology and Disease Using Single-Cell Omics Technologies
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HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling
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- Authors
- Han, K. Y., Kim, K.-T., Joung, J.-G., Son, D.-S., Kim, Y. J., Jo, A., Jeon, H.-J., Moon, H.-S., Yoo, C. E., Chung, W., Eum, H. H., Kim, S., Kim, H. K., Lee, J. E., Ahn, M.-J., Lee, H.-O., Park, D., & Park, W.-Y.
- Affiliations
- Samsung Medical Center (KR)
- Seoul National University (KR)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-12-05
- Volume
- 28
- Issue
- 1
- Pages
- 75-87
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC5749184
- OpenAlex
- W2772851294
- Cited by
- 143
- References
- 53
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 22 · 2023: 24 · 2022: 18 · 2021: 21 · 2020: 13 · 2019: 15 · 2018: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Korea Health Technology R&D Project
- Korea Health Industry Development Institute
- Ministry of Health & Welfare
- Republic of Korea (HI13C2096)
- National Research Foundation of Korea
- Korean Government (2016R1A5A2945889, 2017M3A9G5060264, 2017R1D1A1B03035186)
- NRF
- Ministry of Food & Drug Safety (16173MFDS004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- hypotonic lysis, single-cell transcriptome, copy number variation, single nucleotide variants, genetic heterogeneity, gene expression
- MeSH terms
- DNA, Neoplasm, Humans, Neoplasms, RNA, Neoplasm, High-Throughput Nucleotide Sequencing, MCF-7 Cells
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