Popular computational methods to assess multiprotein complexes derived from label-free affinity purification and mass spectrometry (AP-MS) experiments.

ABSTRACT

Advances in sensitivity, resolution, mass accuracy, and throughput have considerably increased the number of protein identifications made via mass spectrometry. Despite these advances, state-of-the-art experimental methods for the study of protein-protein interactions yield more candidate interactions than may be expected biologically owing to biases and limitations in the experimental methodology. In silico methods, which distinguish between true and false interactions, have been developed and applied successfully to reduce the number of false positive results yielded by physical interaction assays. Such methods may be grouped according to (1) the type of data used methods based on experiment-specific measurements (e.g., spectral counts or identification scores) versus methods that extract knowledge encoded in external annotations (e.g., public interaction and functional categorisation databases); (2) the type of algorithm applied the statistical description and estimation of physical protein properties versus predictive supervised machine learning or text-mining algorithms; (3) the type of protein relation evaluated direct (binary) interaction of two proteins in a cocomplex versus probability of any functional relationship between two proteins (e.g., co-occurrence in a pathway, sub cellular compartment); and (4) initial motivation elucidation of experimental data by evaluation versus prediction of novel protein-protein interaction, to be experimentally validated a posteriori. This work reviews several popular computational scoring methods and software platforms for protein-protein interactions evaluation according to their methodology, comparative strengths and weaknesses, data representation, accessibility, and availability. The scoring methods and platforms described include CompPASS, SAINT, Decontaminator, MINT, IntAct, STRING, and FunCoup. References to related work are provided throughout in order to provide a concise but thorough introduction to a rapidly growing interdisciplinary field of investigation.