Background: The Gene Ontology (GO) provides a controlled vocabulary for describing genes and gene products. In spite of the undoubted importance of GO, several drawbacks associated with GO and GO-based annotations have been introduced. We identified three types of semantic inconsistencies in GO-based annotations; semantically redundant, biological-domain inconsistent and taxonomy inconsistent annotations. Methods: To determine the semantic inconsistencies in GO annotation, we used the hierarchical structure of GO graph and tree structure of NCBI taxonomy. Twenty seven biological databases were collected for finding semantic inconsistent annotation. Results: The distributions and possible causes of the semantic inconsistencies were investigated usingtwenty seven biological databases with GO-based annotations. We found that some evidence codes of annotation were associated with the inconsistencies. The numbers of gene products and species in a database that are related to the complexity of databasemanagement are also in correlation with the inconsistencies. Consequently, numerous annotation errors arise and are propagated throughout biological databases and GO-based high-level analyses. GOChase-ll is developed to detect and correct both syntacticand semantic errors in GO-based annotations. Conclusions: We identified some inconsistencies in GO-based annotation and provided software, GOChase-ll, for correcting these semantic inconsistencies in addition to the previous corrections for the syntacticerrors by GOChase-l.
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