Intrinsic Disorder in Putative Protein Sequences

Intrinsically disordered proteins perform a variety of crucial biological functions despite lacking stable tertiary structure under physiological conditions in vitro. State-of-the-art sequence-based predictors of intrinsic disorder are achieving per-residue accuracies over 80%. In a genome-wide study we observed big difference in predicted disorder content between confirmed and putative human proteins, and suspected that this is due to large errors introduced by gene-finding algorithms for putative sequence annotation. To test this hypothesis we trained a predictor to discriminate sequences of real proteins from synthetic sequences that mimic errors of gene finding algorithms. Its application to putative human protein sequences shows that they contain a substantial fraction of incorrectly assigned regions. These regions are predicted to have higher levels of disorder content than correctly assigned regions. Our finding provides first evidence that current practice of predicting disorder content in putative sequences should be reconsidered, as such estimates are biased.