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Open Access Methodology article

Applying negative rule mining to improve genome annotation

Irena I Artamonova12, Goar Frishman1 and Dmitrij Frishman13*

Author Affiliations

1 Institute for Bioinformatics, GSF – National Research Center for Environment and Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany

2 Group of Bioinformatics, Vavilov Institute of General Genetics RAS, Gubkina 3, 119991 Moscow, Russia

3 Department of Genome Oriented Bioinformatics, Technische Universität Munchen, Wissenschaftzentrum Weihenstephan, 85350 Freising, Germany

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BMC Bioinformatics 2007, 8:261  doi:10.1186/1471-2105-8-261

Published: 21 July 2007



Unsupervised annotation of proteins by software pipelines suffers from very high error rates. Spurious functional assignments are usually caused by unwarranted homology-based transfer of information from existing database entries to the new target sequences. We have previously demonstrated that data mining in large sequence annotation databanks can help identify annotation items that are strongly associated with each other, and that exceptions from strong positive association rules often point to potential annotation errors. Here we investigate the applicability of negative association rule mining to revealing erroneously assigned annotation items.


Almost all exceptions from strong negative association rules are connected to at least one wrong attribute in the feature combination making up the rule. The fraction of annotation features flagged by this approach as suspicious is strongly enriched in errors and constitutes about 0.6% of the whole body of the similarity-transferred annotation in the PEDANT genome database. Positive rule mining does not identify two thirds of these errors. The approach based on exceptions from negative rules is much more specific than positive rule mining, but its coverage is significantly lower.


Mining of both negative and positive association rules is a potent tool for finding significant trends in protein annotation and flagging doubtful features for further inspection.