Inferring chromatin-bound protein complexes from genome-wide binding assays – Genome Research

February 26, 2017

Inferring [w. NMF] chromatin-bound protein complexes [of TFs] from [ENCODE ChIP-seq] binding assays, by @ElementoLab

Giannopoulou E, Elemento O. 2013. Inferring chromatin-bound
protein complexes from genome-wide binding assays. Genome Research, Published in Advance April 3, 2013, doi: 10.1101/gr.149419.112.

This study uses nonnegative matrix factorization (NMF) of ENCODE CHIP-seq data (transcription
factors and histone modifications) to predict complexes of
transcription factors that bind DNA
together; it then assesses how these predicted complexes regulate gene expression. It goes beyond
previous studies in that it attempts to treat the TFs as complexes rather than individuals. A handful of
the predicted complexes correspond to known regulatory complexes, e.g. PRC2, and overall, the
complexes were enriched for known protein-protein interactions. Linear regression and random forest
models were then used to predict the effects of the complexes on the expression of adjacent genes. In
both models, the complexes performed better than those predicted from a scrambled TF read count
matrix. Overall, this study provides a large set of hypotheses for combinations of TFs that may
function together, as well as potential new components of known complexes.