Supplementary Figure 6: Comparison of co-regulation data with AP-MS interactome maps to identify protein complexes. | Nature Biotechnology

Supplementary Figure 6: Comparison of co-regulation data with AP-MS interactome maps to identify protein complexes.

From: Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities

Supplementary Figure 6

Even the conservative cut-off of an FDR of 0.05 % used in our manuscript produces a set of protein-protein associations with 71 % not listed in the CORUM database, a conservatively curated database of known protein complexes. It should be noted that this compares favorably to the two prominent AP-MS studies on mapping the human interactome1,2. Only 6 % of the 23,744 interactions reported by Huttlin et al.1 are listed in the CORUM database and 7 % of the 31,944 interactions presented by Hein et al.2. We have compared our dataset with these AP-MS datasets. For this comparison we only considered associations, where both protein partners were identified in both datasets. This was done to remove experimental bias regarding the identified proteins. The number of associations from our dataset fulfilling this requirement was 8,128, out of which 678 (8 %) were also reported by Huttlin et al.. Out of the 678 associations 501 (74 %) are CORUM listed and 177 (26 %) are novel interactions. The percentage of known interactions in our sub-dataset was 35 % (2,825 associations) and 501 of those (18 %) were confirmed by Huttlin et al., while the 177 unknown interactions confirmed by Huttlin et al. constituted 3 % of the 5,303 unknown associations in our dataset. In summary, the comparison shows that associations found in both dataset are enriched for known associations but that unknown associations was also confirmed by the AP-MS interactome mapping. To put this comparison into perspective, we also compared another AP-MS mapping performed by Hein et al. with that of Huttlin et al. in the exactly same manner. 16,357 associations reported by Hein et al. fulfilled the requirement of both protein-partners being identified in interactions in both datasets. 6 % (998) of them were confirmed by Huttlin et al., of which 390 (39 %) were known and 61 % (608) were novel. Of all the known interactions in the Hein et al. sub-dataset (1,758), 22 % (390) were also found by Huttlin et al.. The overlap was 4 % (608 out of 16357) for the unknown interactions. In summary, we show that novel associations in our dataset are confirmed by AP-MS data and that our dataset compares with AP-MS data in a similar way that AP-MS datasets compare with each other.

1. Huttlin, E. L. et al. The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 162, 425-440, doi:10.1016/j.cell.2015.06.043 (2015).

2. Hein, M. Y. et al. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 163, 712-723, doi:10.1016/j.cell.2015.09.053 (2015).

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