Figure 1.

The scope of different mass spectrometry (MS)-based interactome screens. State of art MS-based approaches for investigating the interactome are summarized. Affinity purification and proximity labelling coupled to MS are targeted strategies for which a high coverage of protein complexes can only be achieved by performing hundreds to ten-thousands of single-bait experiments. The theoretically achievable coverage of cross-linking, co-fractionation and thermal proteome profiling strategies in turn depend on the purification level of the sample, e.g., purified sub-proteome (single complex or organelle) vs. whole cell extract. Finally, full proteome co-variation studies across large MS cohorts are usually not acquired specifically with the purpose of investigating protein interactions, but they can be leveraged to find global patterns of co-variation e.g., to investigate evolutionary conservation of complexes. Exemplary studies for the different approaches are indicated at their respective proteome coverage.