Journal: Nature Communications

Article Title: Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer’s disease

doi: 10.1038/s41467-025-56400-0

Figure Lengend Snippet: a Genomic distribution of all (background) STRs tested (top) compared to AD STRs expansions (bottom). b Distribution of distances to nearest TSS for all STRs tested (top) or AD STR expansions (bottom). c Enrichment of AD STR expansions in different chromatin states from the 18-state chromHMM model for adult hippocampus. d Enrichment of AD STR expansions using a permutation-based test. Dotted vertical line shows the number of AD STR expansions observed to overlap “flanking TSS” (chromatin state 2 from chromHMM) in adult hippocampus using a permutation-based test. e Enrichment of AD expanded STRs in peaks from different histone marks based on ChIP-seq in bulk adult hippocampal tissue. f Enrichment of AD STR expansions in different TE classes. g Enrichment of AD expanded STRs in SVA elements using a permutation-based test. h Proportion of STRs at given genomic distances from the nearest SVA. For c , e , f , height of points along the x-axis represents the statistical significance of enrichment, as measured by two-sided Fisher’s exact test. Size of points represents the magnitude of enrichment as represented by the log 2 (fold enrichment), and points are ordered by statistical significance for enrichment. For d , g dotted line reflects the observed number of AD STR expansions overlapping the genomic annotation, and histogram represents the number of AD STR expansions overlapping each of 1000 randomly permuted genomic regions. For d , g p -values represent empiric p -values calculated as the number of permutations exceeding observed STR overlap divided by total number of permutations.

Article Snippet: We downloaded chromHMM partitions under the 18 state model for the adult human hippocampus (ENCODE tissue ID E071) from the Roadmap Epigenomics Consortium ( https://egg2.wustl.edu/roadmap/web_portal/chr_state_learning.html ) , .

Techniques: ChIP-sequencing

Journal: Molecular Oncology

Article Title: Cis‐regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers

doi: 10.1002/1878-0261.13559

Figure Lengend Snippet: Enrichment of HPV integrations in functionally annotated regions. (A) Enrichment of HPV integrations in the ChromHMM annotated regions from the HeLa cell line. The x ‐axis represents the log of observed/expected number of HPV integrations. The y ‐axis represents the different annotations and the observed number of HPV integrations overlapping them (given in the bracket). The P ‐values were computed using Chi‐squared goodness‐of‐fit test followed by FDR correction. The colour of the dots indicates whether the adjusted P ‐value is below the significance level of 5% or not. (B) Same as (A) but with ChromHMM annotations from the NHEK cell line. (C, D) Bar plot showing the frequency of observed and expected integrations in the active and inactive regions defined by combining ChromHMM annotations in HeLa (C) and NHEK (D) (see Section ). The P ‐value was calculated using a one‐sample Chi‐squared test. (E) Enrichment of HPV integration in various histone modification regions from HeLa and NHEK. The x ‐axis represents the log of observed/expected number of HPV integrations and the y ‐axis represents the negative log 10 of adjusted P ‐value (Chi‐squared test followed by FDR correction). The horizontal dashed line represents FDR cut‐off of 5%. The colour and size of the dots represent the cell line and the number of observed HPV integrations for each of the histone marks, respectively.

Article Snippet: With both HeLa and NHEK ChromHMM annotations, we observed that compared to the expected, HPV integrations were significantly enriched (Chi‐squared test, FDR < 0.05) in the transcriptionally active regions (TxFlnk, Tx, TxWk), enhancers (EnhG, Enh), and zinc finger protein gene/repeat regions (ZNF/Rpts); whereas a significant depletion (FDR < 0.05) was observed in polycomb repressed/heterochromatin regions (ReprPC, ReprPCWk, Het), and quiescent regions (Quies; in NHEK but not in HeLa) (Fig. ).

Techniques: Modification

Journal: Molecular Oncology

Article Title: Cis‐regulatory effect of HPV integration is constrained by host chromatin architecture in cervical cancers

doi: 10.1002/1878-0261.13559

Figure Lengend Snippet: Enhanced transcriptional activity near HPV integration in the context of chromatin states from HeLa. (A) Boxplot showing the total expression in the 10 kb flanking region around the HPV integration regions as compared to mean expression from TCGA‐CESC samples without HPV integration in the same region. In the boxplot, the horizontal middle line indicates the median, the height of the shaded box indicates the interquartile range (IQR) and the whiskers indicate 1.5 × IQR. The x ‐axis represents whether the HPV integration is located in an inactive ( n = 97) or active ( n = 54) chromatin regions with respect to HeLa ChromHMM. The P ‐values were computed using Mann–Whitney U test (two‐sided). (B) Same as (A) but for the eRNA expression from SEs (if any) within 10 kb on either side of the HPV integration regions located in inactive ( n = 35) or active ( n = 43) chromatin regions. (C) Expression fold change associated with each of the HPV integration regions. The x ‐axis represents the log 2 fold change, which was calculated as the total expression in the 10 kb flanking region around HPV integration regions divided by the mean expression from other samples without HPV integration in the same genomic region. The y ‐axis represents the individual sample‐id of TCGA‐CESC samples. The colour of the dots indicates if the integration overlaps an active or inactive ChromHMM region of HeLa. The black vertical line represents the value of log 2 (fc + 1) = 1. The histogram at the bottom shows the frequency of integration regions at different fold‐change bins. Each dot in (A–C) represents a HPV integration region from a sample.

Article Snippet: With both HeLa and NHEK ChromHMM annotations, we observed that compared to the expected, HPV integrations were significantly enriched (Chi‐squared test, FDR < 0.05) in the transcriptionally active regions (TxFlnk, Tx, TxWk), enhancers (EnhG, Enh), and zinc finger protein gene/repeat regions (ZNF/Rpts); whereas a significant depletion (FDR < 0.05) was observed in polycomb repressed/heterochromatin regions (ReprPC, ReprPCWk, Het), and quiescent regions (Quies; in NHEK but not in HeLa) (Fig. ).

Techniques: Activity Assay, Expressing, MANN-WHITNEY

Journal: Cancer cell

Article Title: KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer

doi: 10.1016/j.ccell.2020.03.005

Figure Lengend Snippet: (A) Emission probabilities of the 10-state ChromHMM model calculated from six histone modification profiles in Kras and Kras;Kmt2d−/− lung tumors. Each row represents one chromatin state. The 10 states predicted using ChromHMM represent various enhancer states (E2, E3, E4, E5, and E7), promoter state (E1), transcription states (E1, E6, and E7), polycomb-repressed state (E10), and heterochromatin state (E8). Each column corresponds to a histone modification. The intensity of the color in the scale from 0 (white) to 1 (red) in each cell reflects the frequency of occurrence of each histone mark in the indicated chromatin state. (B) Heat map showing the fold enrichment of transitions of chromatin states from Kras lung tumors to Kras;Kmt2d−/− lung tumors. The color intensities represent the relative fold enrichment. (C and D) Heat maps (left panels) and average intensity curves (right panels) of ChIP-seq reads (RPKM) for H3K27ac (C) and H3K4me1 (D) at typical enhancer regions. Enhancers are shown in a 10-kb window (centered on the middle of the enhancer) in Kras and Kras;Kmt2d−/− lung tumors. (E and F) Heat maps (left panel) and average intensity curves (right panels) of ChIP-seq reads for H3K27ac (E) and H3K4me1 (F) at the super-enhancer regions plus their flanking 2-kb regions in Kras and Kras;Kmt2d−/− lung tumors. Wilcoxon rank sum test was used for statistical analysis of (C–F). T1, tumor 1; T2, tumor 2. See also Figures S3 and S4.

Article Snippet: ChromHMM profiles of two Kras;Kmt2d −/− and two Kras samples were consolidated using Epilogos ( https://github.com/Altius/epilogos ).

Techniques: Modification, ChIP-sequencing