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Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

Fig 2

PLC NCVs occur more often than expected in heterologous cell type-specific regulatory elements.

(a) Filtering strategy for SNVs from whole genome resequenced samples in COSMIC. (b) Annotation of filtered SNVs by UCSC known genes. (c) SNVs in cell type restricted or shared DNaseI promoters or enhancers. Y-axis is fold observed over expected, based on background distribution of cell type restricted or shared DHSs. (d) Observed versus expected SNVs in each ChromHMM-18 state in each of the 78 Roadmap cells and tissues with available data. Orange dot is primary liver sample (Roadmap E066); gray dots are the other 77 Roadmap samples; black line is 1. (e) Browser view of C1orf61 locus and three regulatory elements mutated in three unique samples. The top track is the Epilogos track (http://compbio.mit.edu/epilogos/), which provides a visualization of the chromatin state models for several cell types at once. The presented track depicts the ChromHMM-18 state model 127 Roadmap cell types (primary and cell lines) at a 200bp resolution. Red and orange colors represent active promoter annotations; light green and yellow colors represent genic enhancers and enhancers, respectively; pink and beige are bivalent states; grays are repressed Polycomb states. Middle track: Positions of PLC WGS SNVs (red lines) on a yellow background. Bottom track: RefSeq genes track. (f) Expression from TCGA PLC tumor and matched normal samples for C1orf61. Red line = median expression for normal samples. (g) Browser view for ESRP1 and three regulatory elements mutated in three unique samples. Tracks are as in (e). (h) Expression as in (f) for ESRP1.

Fig 2

doi: https://doi.org/10.1371/journal.pone.0174032.g002