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RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.

Publication ,  Journal Article
Mitra, S; Zhong, J; Tran, TQ; MacAlpine, DM; Hartemink, AJ
Published in: Nucleic Acids Res
August 20, 2021

Chromatin is a tightly packaged structure of DNA and protein within the nucleus of a cell. The arrangement of different protein complexes along the DNA modulates and is modulated by gene expression. Measuring the binding locations and occupancy levels of different transcription factors (TFs) and nucleosomes is therefore crucial to understanding gene regulation. Antibody-based methods for assaying chromatin occupancy are capable of identifying the binding sites of specific DNA binding factors, but only one factor at a time. In contrast, epigenomic accessibility data like MNase-seq, DNase-seq, and ATAC-seq provide insight into the chromatin landscape of all factors bound along the genome, but with little insight into the identities of those factors. Here, we present RoboCOP, a multivariate state space model that integrates chromatin accessibility data with nucleotide sequence to jointly compute genome-wide probabilistic scores of nucleosome and TF occupancy, for hundreds of different factors. We apply RoboCOP to MNase-seq and ATAC-seq data to elucidate the protein-binding landscape of nucleosomes and 150 TFs across the yeast genome, and show that our model makes better predictions than existing methods. We also compute a chromatin occupancy profile of the yeast genome under cadmium stress, revealing chromatin dynamics associated with transcriptional regulation.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

August 20, 2021

Volume

49

Issue

14

Start / End Page

7925 / 7938

Location

England

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae
  • RNA-Seq
  • Nucleosomes
  • Mutation
  • High-Throughput Nucleotide Sequencing
  • Genome, Fungal
  • Gene Expression Regulation, Fungal
  • Developmental Biology
  • Computational Biology
 

Citation

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Mitra, S., Zhong, J., Tran, T. Q., MacAlpine, D. M., & Hartemink, A. J. (2021). RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data. Nucleic Acids Res, 49(14), 7925–7938. https://doi.org/10.1093/nar/gkab553
Mitra, Sneha, Jianling Zhong, Trung Q. Tran, David M. MacAlpine, and Alexander J. Hartemink. “RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.Nucleic Acids Res 49, no. 14 (August 20, 2021): 7925–38. https://doi.org/10.1093/nar/gkab553.
Mitra S, Zhong J, Tran TQ, MacAlpine DM, Hartemink AJ. RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data. Nucleic Acids Res. 2021 Aug 20;49(14):7925–38.
Mitra, Sneha, et al. “RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data.Nucleic Acids Res, vol. 49, no. 14, Aug. 2021, pp. 7925–38. Pubmed, doi:10.1093/nar/gkab553.
Mitra S, Zhong J, Tran TQ, MacAlpine DM, Hartemink AJ. RoboCOP: jointly computing chromatin occupancy profiles for numerous factors from chromatin accessibility data. Nucleic Acids Res. 2021 Aug 20;49(14):7925–7938.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

August 20, 2021

Volume

49

Issue

14

Start / End Page

7925 / 7938

Location

England

Related Subject Headings

  • Transcription Factors
  • Saccharomyces cerevisiae
  • RNA-Seq
  • Nucleosomes
  • Mutation
  • High-Throughput Nucleotide Sequencing
  • Genome, Fungal
  • Gene Expression Regulation, Fungal
  • Developmental Biology
  • Computational Biology