A computational framework for the inference of protein complex remodeling from whole-proteome measurements.

ABSTRACT

Protein complexes are responsible for the enactment of most cellular functions. For the protein complex to form and function, its subunits often need to be present at defined quantitative ratios. Typically, global changes in protein complex composition are assessed with experimental approaches that tend to be time consuming. Here, we have developed a computational algorithm for the detection of altered protein complexes based on the systematic assessment of subunit ratios from quantitative proteomic measurements. We applied it to measurements from breast cancer cell lines and patient biopsies and were able to identify strong remodeling of HDAC2 epigenetic complexes in more aggressive forms of cancer. The presented algorithm is available as an R package and enables the inference of changes in protein complex states by extracting functionally relevant information from bottom-up proteomic datasets.