PT  - JOURNAL ARTICLE
AU  - Rao, Jingyou
AU  - Wang, Mingsen
AU  - Howard, Matthew K
AU  - Macdonald, Christian
AU  - Fraser, James S.
AU  - Coyote-Maestas, Willow
AU  - Pimentel, Harold
TI  - Rosace-AA: Enhancing Interpretation of Deep Mutational Scanning Data with Amino Acid Substitution and Position-Specific Insights
AID  - 10.1101/2025.01.09.632281
DP  - 2025 Jan 01
TA  - bioRxiv
PG  - 2025.01.09.632281
4099  - http://biorxiv.org/content/early/2025/01/14/2025.01.09.632281.short
4100  - http://biorxiv.org/content/early/2025/01/14/2025.01.09.632281.full
AB  - Proteins are dynamic systems whose function and behavior are sensitive to environmental conditions and often involve multiple cellular roles. Deep mutational scanning (DMS) experiments generate extensive datasets to capture the functional consequences of mutations. However, the sheer volume of data presents challenges in visualization and interpretation. Current approaches often rely on heatmaps, but these methods fail to capture the nuanced effects of amino acid (AA) substitutions, which are essential for understanding mutational impact. To address this, we extend the Rosace framework with Rosace-AA, a model that incorporates both position-specific information and AA substitution trends. Using substitution matrices like BLOSUM90, Rosace-AA offers a flexible and interpretable approach to summarize DMS data oil both protein-level and position-level. We demonstrate its utility across datasets, including OCTI and MET kinase, showing that Rosace-AA highlights key positions where mutations deviate from expected substitution patterns and captures functionally relevant variation in protein behavior across multiple DMS screens. These results suggest that Rosace-AA enables more robust and interpretable analysis of complex DMS datasets.Competing Interest StatementThe authors have declared no competing interest.