Fig. 1.

Analytical procedure. Starting from the IgG glycan abundances measured using LC-ESI-MS (1), we calculated a correlation-based network (2) and mapped it to the known IgG glycosylation pathway (3). We found that most edges in the network corresponded to single enzymatic steps in the pathway (4). Based on this finding, we inferred unknown enzymatic reactions that were putatively involved in the synthesis of IgG glycans using a rule-based approach (5). We then replicated the findings using four cohorts (6) and performed different in vitro validation experiments to confirm the predicted reactions (7)