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Nucleic Acids Research
Article . 2025 . Peer-reviewed
License: CC BY
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https://doi.org/10.1101/2023.0...
Article . 2023 . Peer-reviewed
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Telomemore enables single-cell analysis of cell cycle and chromatin condensation

Authors: Iryna Yakovenko; Ionut S Mihai; Martin Selinger; William Rosenbaum; Andy Dernstedt; Remigius Groning; Johan Trygg; +3 Authors

Telomemore enables single-cell analysis of cell cycle and chromatin condensation

Abstract

Abstract Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites. Here, we show that ATAC-seq telomere-like reads counter-inituively cannot be used to infer telomere length, as they mostly originate from the subtelomere, but can be used as a biomarker for chromatin condensation. Using long-read sequencing, we further show that modern hyperactive Tn5 does not duplicate 9 bp of its target sequence, contrary to common belief. We provide a new tool, Telomemore, which can quantify nonaligning subtelomeric reads. By analyzing several public datasets and generating new multiome fibroblast and B-cell atlases, we show how this new readout can aid single-cell data interpretation. We show how drivers of condensation processes can be inferred, and how it complements common RNA-seq-based cell cycle inference, which fails for monocytes. Telomemore-based analysis of the condensation state is thus a valuable complement to the single-cell analysis toolbox.

Country
Sweden
Keywords

B-Lymphocytes, Molekylärbiologi, Binding Sites, Cell Cycle, Computational Biology, Telomere, Fibroblasts, Medicinsk genetik och genomik, Chromatin, Medical Genetics and Genomics, Mice, Medical Bioinformatics and Systems Biology, Humans, Chromatin Immunoprecipitation Sequencing, RNA-Seq, Medicinsk bioinformatik och systembiologi, Single-Cell Analysis, Molecular Biology

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
Green
gold
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