Accurate estimation of intrinsic biases for improved analysis of bulk and single-cell chromatin accessibility sequencing data using SELMA

Hu, Shengen; Liu, Lin; Li, Qi; Ma, Wenjing; Guertin, Michael J.; Meyer, Clifford A.; Deng, Ke; Zhang, Tingting; Zang, Chongzhi

doi:10.1101/2021.10.22.465530

Cited by 3 publications

(3 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regardless of the technique used, around half of the detected origins fall in intergenic regions, followed by 30–40% allocated to introns ( Figure 1d ). We recently reported 40,110 genomic regions are routinely bound by more than 3000 transcription factor (TF) ChIP-seq data, named as TF-binding hotspots ( Hu et al, 2021 ). These TF-binding hotspots likely represent highly active open chromatin regions.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Tian,

Wang,

et al. 2024

eLife

Self Cite

View full text Add to dashboard Cite

DNA replication initiates from ∼50,000 origins on human chromosomes in each cell-cycle and the origins are hypothesized to be specified by binding of factors like the Origin Recognition Complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and 5 ORC-binding site datasets to critically evaluate whether the most reproducible origins are specified by these features. Out of ∼7.5 million 300 bp chromosomal fragments reported to harbor origins by all the datasets, only 0.27% were reproducibly detected by four techniques (20,250 shared origins), suggesting extensive variability in origin usage and identification in different circumstances. 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF binding sites, G-quadruplex sites and activating histone marks, these overlaps are comparable or less than that of known Transcription Start Sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ∼13,000 reproducible ORC binding sites in human cancer cells, in contrast to the nearly 100% overlap between the two in the yeast, S. cerevisiae. Thus, in human cancer cell-lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and ORC-binding sites.

show abstract

Section: Resultsmentioning

confidence: 99%

“…1d ). We recently reported 40,110 genomic regions are routinely bound by more than 3000 TF ChIP-seq data, named as TF binding hotspots (Hu et al 2021 ). These TF binding hotspots likely represent highly active open chromatin regions.…”

Section: A Total Of 7459709 Origins From 113 Datasets Show Similar Bu...mentioning

confidence: 99%

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Tian,

Wang,

et al. 2024

eLife

Self Cite

View full text Add to dashboard Cite

show abstract

“…1d). We recently reported 40,110 genomic regions are routinely bound by more than 3000 TF ChIP-seq data, named as TF binding hotspots (Hu et al 2021).…”

Section: A Total Of 7459709 Origins From 113 Datasets Show Similar Bu...mentioning

confidence: 99%

Integrative analysis of DNA replication origins and ORC/MCM binding sites in human cells reveals a lack of overlap

Tian¹,

Wang²,

Su³

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

DNA replication initiates from ~50,000 origins on human chromosomes in each cell-cycle and the origins are hypothesized to be specified by binding of factors like the Origin Recognition Complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and 5 ORC-binding site datasets to critically evaluate whether the most reproducible origins are specified by these features. Out of ~7.5 million 300 bp chromosomal fragments reported to harbor origins by all the datasets, only 0.27% were reproducibly detected by four techniques (20,250 shared origins), suggesting extensive variability in origin usage and identification in different circumstances. 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF binding sites, G-quadruplex sites and activating histone marks, these overlaps are comparable or less than that of known Transcription Start Sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ~13,000 reproducible ORC binding sites in human cancer cells, in contrast to the nearly 100% overlap between the two in the yeast, S. cerevisiae. Thus, in human cancer cell-lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and ORC-binding sites.

show abstract

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Tian,

Wang,

et al. 2024

eLife

View full text Add to dashboard Cite

Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the origin recognition complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and five ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features. Out of ~7.5 million union origins identified by all datasets, only 0.27% (20,250 shared origins) were reproducibly obtained in at least 20 independent SNS-seq datasets and contained in initiation zones identified by each of three other techniques, suggesting extensive variability in origin usage and identification. Also, 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF-binding sites, G-quadruplex sites, and activating histone marks, these overlaps are comparable or less than that of known transcription start sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ~13,000 reproducible ORC-binding sites in human cancer cells, and only 4.5% were within 1 kb of the ~11,000 union MCM2-7-binding sites in contrast to the nearly 100% overlap in the two comparisons in the yeast, Saccharomyces cerevisiae. Thus, in human cancer cell lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and currently known ORC- or MCM-binding sites.

show abstract

Accurate estimation of intrinsic biases for improved analysis of bulk and single-cell chromatin accessibility sequencing data using SELMA

Cited by 3 publications

References 54 publications

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Integrative analysis of DNA replication origins and ORC/MCM binding sites in human cells reveals a lack of overlap

Integrative analysis of DNA replication origins and ORC-/MCM-binding sites in human cells reveals a lack of overlap

Contact Info

Product

Resources

About