Table 4.

Summary of approaches that address sources of uncertainty in network gap-filling. While all gap-filling approaches address uncertainty arising from missing annotations, here we point out approaches that address uncertainty in the gap-filling solutions. Highlighted in bold are key approaches related to probabilistic or ensemble-based methods

Approach	Sources of uncertainty	References
Evaluating gap-filling accuracy	Degenerate solutions	[109, 110]
Probabilistic gap-filling	Degenerate solutions	[44, 45, 112, 113]
Ensemble gap-filling	Degenerate solutions	[43, 114–116]
De novo reaction prediction	Reaction database incompleteness	[121–124]