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dc.contributor.advisorKellis, Manolis
dc.contributor.advisorZitnik, Marinka
dc.contributor.authorCalef, Robert
dc.date.accessioned2025-11-17T19:08:47Z
dc.date.available2025-11-17T19:08:47Z
dc.date.issued2025-05
dc.date.submitted2025-08-14T19:31:20.340Z
dc.identifier.urihttps://hdl.handle.net/1721.1/163712
dc.description.abstractUnderstanding the roles of human proteins remains a major challenge, with approximately 20% of human proteins lacking known functions and more than 40% missing context-specific functional insights. Even well-annotated proteins are often poorly characterized in diverse biological contexts, disease states, and perturbations. We present ProCyon, a foundation model for modeling, generating, and predicting protein phenotypes across five interrelated knowledge domains: molecular functions, therapeutic mechanisms, disease associations, functional protein domains, and molecular interactions. To support this, we created ProCyon-Instruct, a dataset of 33 million protein phenotype instructions, representing a comprehensive resource for multiscale protein phenotypes. By co-training a large language model with multimodal molecular encoders, ProCyon integrates phenotypic and protein data. A novel architecture and instruction tuning strategy allow ProCyon to process arbitrarily interleaved proteinand-phenotype inputs, achieve zero-shot task transfer, and generate free-form text phenotypes interleaved with retrieved protein sequence, structure, and drug modalities in a single unified model.
dc.publisherMassachusetts Institute of Technology
dc.rightsIn Copyright - Educational Use Permitted
dc.rightsCopyright retained by author(s)
dc.rights.urihttps://rightsstatements.org/page/InC-EDU/1.0/
dc.titleFoundation Models for Protein Phenotype Prediction
dc.typeThesis
dc.description.degreeS.M.
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
mit.thesis.degreeMaster
thesis.degree.nameMaster of Science in Electrical Engineering and Computer Science


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