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Universal chromatin state annotation of the mouse genome

Vu, Ha, Ernst, Jason·2023·Genome Biology
DOI 10.1186/s13059-023-02994-xPMC PMC10294404

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Abstract

A large-scale application of the “stacked modeling” approach for chromatin state discovery previously provides a single “universal” chromatin state annotation of the human genome based jointly on data from many cell and tissue types. Here, we produce an analogous chromatin state annotation for mouse based on 901 datasets assaying 14 chromatin marks in 26 cell or tissue types. To characterize each chromatin state, we relate the states to external annotations and compare them to analogously defined human states. We expect the universal chromatin state annotation for mouse to be a useful resource for studying this key model organism’s genome.

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Fig. 1 Mouse full-stack state emission parameters. A Each of the 100 rows in the heatmap corresponds to a mouse full-stack state. Each of the 901 columns corresponds to one input dataset. For each state and each dataset, the heatmap gives the probability within the state of observing a binary present call for the dataset’s signal. Above the heatmap, the first color bar indicates the assay/chromatin mark measured by each dataset. The second color bar shows the cell type groups associated with each dataset. The corresponding color legends are shown towards the bottom. The states are displayed in 16 groups based on biological interpretations indicated by the color legend at the bottom, with white space between each group. Full characterization of states is available in Additional file 2. The model’s transition parameters between states can be found in Additional file 1: Fig. S1. Columns are ordered such that datasets profiling the same chromatin marks are next to each other. B Each row corresponds to a full-stack state as ordered in A. The columns correspond to the top 10 datasets with the highest emission value for each state, in order of decreasing ranks, colored by their associated chromatin marks as in A. C Similar to B, but datasets are colored by the associated cell type groups. The cell type groups primarily associated with some of the enhancer states are noted inside the heatmap. A fully annotated version of Fig. 2B–C is provided in Additional file 3
Fig. 1 Mouse full-stack state emission parameters. A Each of the 100 rows in the heatmap corresponds to a mouse full-stack state. Each of the 901 columns corresponds to one input dataset. For each state and each dataset, the heatmap gives the probability within the state of observing a binary present call for the dataset’s signal. Above the heatmap, the first color bar indicates the assay/chromatin mark measured by each dataset. The second color bar shows the cell type groups associated with each dataset. The corresponding color legends are shown towards the bottom. The states are displayed in 16 groups based on biological interpretations indicated by the color legend at the bottom, with white space between each group. Full characterization of states is available in Additional file 2. The model’s transition parameters between states can be found in Additional file 1: Fig. S1. Columns are ordered such that datasets profiling the same chromatin marks are next to each other. B Each row corresponds to a full-stack state as ordered in A. The columns correspond to the top 10 datasets with the highest emission value for each state, in order of decreasing ranks, colored by their associated chromatin marks as in A. C Similar to B, but datasets are colored by the associated cell type groups. The cell type groups primarily associated with some of the enhancer states are noted inside the heatmap. A fully annotated version of Fig. 2B–C is provided in Additional file 3CC BY · PubMed Central
Fig. 2 Mouse full-stack state enrichments for external genomic annotations. A Fold enrichments of mouse full-stack states with external genome annotations (“Methods” section). Each row corresponds to a state and each column corresponds to one external genomic annotation: coding sequences, CpG islands, exons, gene bodies (exons and introns), transcription end sites (TES), transcription start sites (TSS), TSS and 2-kb surrounding regions, assembly gaps, pseudogenes, blacklisted regions, repeat elements, annotated Zfp genes, and PhastCons conserved elements (“Methods” section). The last row shows the percentage of the genome that each external genome annotation covers. The heatmap colors are column-normalized, i.e., within each column, the colors of the cells are such that the highest values are colored red and the lowest values are colored white. B Each row indicates the states’ average LECIF score, indicating evidence at the functional genomics level of human-mouse conservation based on epigenetic annotations [22] (“Methods” section). The list of states with top average LECIF scores and highest enrichments with PhastCons elements is in Additional file 1: Fig. S9 and Additional file 4. C Average weighted expression of genes that overlap each full-stack state in different groups of cell types (“Methods” section). Each column in the heatmap corresponds to a cell group indicated at the top. Each row corresponds to a state, as ordered in A. D, E Positional enrichments of full-stack states relative to annotated D transcription start sites (TSS) and E transcription end sites (TES). Positive coordinate values represent the number of bases downstream in the 5′ to 3′ direction of transcription, while negative values represent the number of bases upstream. Each line shows the positional enrichments in a state. Lines are colored corresponding to the state group as indicated in A. F Geometric mean and geometric standard deviation of enrichments of full-stack states CTCF elements across 28 cell types (“Methods” section). States are displayed vertically in the same order as A. The mOpenC6-7 state showed the strongest enrichment for CTCF elements in all observed cell types. The geometric mean and standard deviation are calculated such that for each state, fold enrichment values of 0 are replaced by the state’s minimum non-zero value. The fold enrichment values accompanying this plot are available in Additional file 4
Fig. 2 Mouse full-stack state enrichments for external genomic annotations. A Fold enrichments of mouse full-stack states with external genome annotations (“Methods” section). Each row corresponds to a state and each column corresponds to one external genomic annotation: coding sequences, CpG islands, exons, gene bodies (exons and introns), transcription end sites (TES), transcription start sites (TSS), TSS and 2-kb surrounding regions, assembly gaps, pseudogenes, blacklisted regions, repeat elements, annotated Zfp genes, and PhastCons conserved elements (“Methods” section). The last row shows the percentage of the genome that each external genome annotation covers. The heatmap colors are column-normalized, i.e., within each column, the colors of the cells are such that the highest values are colored red and the lowest values are colored white. B Each row indicates the states’ average LECIF score, indicating evidence at the functional genomics level of human-mouse conservation based on epigenetic annotations [22] (“Methods” section). The list of states with top average LECIF scores and highest enrichments with PhastCons elements is in Additional file 1: Fig. S9 and Additional file 4. C Average weighted expression of genes that overlap each full-stack state in different groups of cell types (“Methods” section). Each column in the heatmap corresponds to a cell group indicated at the top. Each row corresponds to a state, as ordered in A. D, E Positional enrichments of full-stack states relative to annotated D transcription start sites (TSS) and E transcription end sites (TES). Positive coordinate values represent the number of bases downstream in the 5′ to 3′ direction of transcription, while negative values represent the number of bases upstream. Each line shows the positional enrichments in a state. Lines are colored corresponding to the state group as indicated in A. F Geometric mean and geometric standard deviation of enrichments of full-stack states CTCF elements across 28 cell types (“Methods” section). States are displayed vertically in the same order as A. The mOpenC6-7 state showed the strongest enrichment for CTCF elements in all observed cell types. The geometric mean and standard deviation are calculated such that for each state, fold enrichment values of 0 are replaced by the state’s minimum non-zero value. The fold enrichment values accompanying this plot are available in Additional file 4CC BY · PubMed Central

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Citations

Cites

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Research works printed but not linked: 33

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Metadata

Authors
Vu, H., & Ernst, J.
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2023-06-27
Volume
24
Issue
1
ISSN
1474-760X
DOI
10.1186/s13059-023-02994-x
PMC
PMC10294404
Cited by
37
References
5
Language
en
Licence
Funders
  • National Institute of Health (DP1DA044371, UH3NS104095, U01HG012079)
  • National Science Foundation (2125664, 1254200)
  • UCLA Jonsson Comprehensive Cancer Center and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles (Ablon Scholars Program)
  • National Institutes of Health (U01MH130995, U01MH105578)
  • Rose Hills Foundation (Rose Hills Innovator Award)

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Vu, H., & Ernst, J. (2023). Universal chromatin state annotation of the mouse genome. Genome Biology. https://doi.org/10.1186/s13059-023-02994-x