Probabilistic Annotations of Protein Sequences for Intrinsically Disordered Features

This paper introduces a novel platform for IDR Probabilistic Annotation (IPA). The IPA platform now encompasses tools for predicting ‘Linker’ regions and ‘nucleic’, ‘protein’, and ‘all’ (protein or nucleic) IDR binding sites within protein amino acid sequences. Despite its simplicity and computational efficiency, results demonstrate that IPA performs competitively with leading tools in predicting ‘protein’ and ‘all’ IDR binding sites while considerably outperforming all tools in identifying Linker regions and nucleic binding sites. An important contribution of this work is the introduction of a new output paradigm for computational feature predictions. Traditional tools typically express predictions as scores, with higher values indicating greater probabilities. However, these scores lack true probabilistic meaning and interpretability, even derived from logistic regression models. This limitation arises primarily because training data priors differ from broader populations’ unknown priors. This paper proposes applying a reverse Bayes Rule to logistic regression outputs, effectively normalizing for the priors in the training data. This adjustment produces scores representing actual probabilities, assuming 50% priors in the general population. Such scores are interpretable in isolation and enable comparability and integration across different tools, marking a significant step toward standardization in feature prediction methodologies.