AstraROLE & AstraSUIT: Multi-Task Annotation Models for Functional Profiling of Proteins

Bozkurt, C.; Vasilyeva, A.; Goteti, A.

doi:10.1101/2025.06.21.660734

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bioRxiv · 10.1101/2025.06.21.660734

AstraROLE & AstraSUIT: Multi-Task Annotation Models for Functional Profiling of Proteins

Bozkurt, C.·Vasilyeva, A.·Goteti, A.

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Abstract

AbstractMost in-silico protein characterisation tools focus on only one aspect of protein function, forcing researchers to use multiple models or to bypass computational checks. Here we introduce AO_SCPLOWSTRAC_SCPLOWROLE2 and AO_SCPLOWSTRAC_SCPLOWSUIT2, two transformer-based, multi-task annotators that deliver an integrated functional profile in a single pass. A 1,351-dimensional input (ESM-2 CLS embeddings plus physicochemical Orbion enrichments) is mapped by a 512-unit encoder and task-specific linear heads: four in AO_SCPLOWSTRAC_SCPLOWROLE2 (EC class, GO term, molecular pathway, protein category) and nine in AO_SCPLOWSTRAC_SCPLOWSUIT2 (cofactor group, specific cofactor, domain, host, membrane association type, transmembrane helix number, subcellular localization, quaternary category, quaternary stoichiometry). Models were trained on 730k UniProt proteins with stratified 70/15/15 splits; class-weighted BCE and Optuna hyper-parameter search countered imbalance. On hold-out sets the heads reached macro F1=0.84-0.98 and MCC=0.85-0.98. Highest scores were seen for cofactor binding (0.98), membrane association type (F1=0.97) and top-level EC number (0.96); GO term classification was hardest (0.85). Against recent comparators (incl. DeepGOPlus and TargetP 2.0), the Astra models matched or exceeded performance, especially on metal-ion binding and cofactor binding. Additional tests on three novel proteins not included in initial dataset showed good predictions for most labels, underscoring the potential for hypothesis generation. Overall, AO_SCPLOWSTRAC_SCPLOWROLE2 and AO_SCPLOWSTRAC_SCPLOWSUIT2 supplied fast, state-of-the-art multi-label protein annotation within one unified model network.

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Bozkurt, C., Vasilyeva, A., Goteti, A.. 2025-06-26. AstraROLE & AstraSUIT: Multi-Task Annotation Models for Functional Profiling of Proteins. https://doi.org/10.1101/2025.06.21.660734

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