The round-trip coverage is calculated in a similar fashion to the round-trip accuracy as shown in Equation S1. The difference lies in the indicator function -the index set is PC. The set PC is the superset of all predicted reaction outcomes p for all target molecules in the test database. Therefore, P C ≡ {p1,1, p1,2, p2,1, p2,2, . . . , p k,1 , p k,2 } and P C ∈ R k×n (note that n = 2). Formally, the round-trip coverage is given through: