Melanoma-patient-derived xenograft multi-omics resource melPDomiX maps gain- and loss-of-function alterations.

Melanoma is a common and aggressive cancer, with rising incidence in most developed countries. Major discoveries in melanoma biology have been rapidly translated, allowing cures for patients in late-stage disease. Despite these advances, many tumors remain refractory, in part due to an incomplete understanding of the genes and pathways gained or lost during melanoma tumorigenesis. To address this gap and provide a broadly useful resource for the scientific community, we established melPDomiX, a multi-omics cohort of melanoma-patient-derived xenografts. By linking mutations with transcriptomic and proteomic features, melPDomiX enables systematic characterization of gain- and loss-of-function alterations in treatment-refractory melanoma. Using multi-omics integration and structural-context representation, we demonstrate how this resource distinguishes gain- from loss-of-function variants and uncovers new candidate melanoma drivers and therapeutic targets. Together, melPDomiX provides a comprehensive, deeply profiled set of tumor models that supports mechanistic discovery and facilitates the development of improved treatments for this devastating heterogeneous malignancy.