: Accurate topology prediction of transmembrane xcexb2-barrels is still an open question. Here, we present BOCTOPUS2, an improved topology prediction method for transmembrane xcexb2-barrels that can also identify the barrel domain, predict the topology and identify the orientation of residues in transmembrane xcexb2-strands. The major novelty of BOCTOPUS2 is the use of the dyad-repeat pattern of lipid and pore facing residues observed in transmembrane xcexb2-barrels. In a cross-validation test on a benchmark set of 42 proteins, BOCTOPUS2 predicts the correct topology in 69% of the proteins, an improvement of more than 10% over the best earlier method (BOCTOPUS) and in addition, it produces significantly fewer erroneous predictions on non-transmembrane xcexb2-barrel proteins.