Distal regulatory elements define myeloma subtype gene expression.
A, t-SNE analysis of gene expression data (left), transcription
at promoter proximal (middle) and distal (right) regulatory elements. Samples
are colored by myeloma gene expression subtype (key bottom). B,
t-SNE distance between samples within a given subtype (denoted by color) for
mRNA as well as promoter proximal and distal regulatory elements.
***P<0.001, **P<0.01, *P<0.05, NS: not significant;
determined by a paired Mann-Whitney U test. C, Genome plot of
regions distinctly regulated between myeloma subtypes near the
CCND2 locus. Regulatory elements (REs) are denoted on top
with cumulative ATAC (RPPM) and H3K27ac (RPM) signal shown and mean
transcription is shown (log2(RPM+1)) for each myeloma subtype. Transcription for
the shaded region is shown (right). D, Scatterplot of
CCND2 expression and regulatory element transcription.