Zwiebel, M.; Wahle, M.; Stadler, R.; Levesque, M. P.; Dummer, R.; Nordmann, T. M.; Mann, M.

The genome and proteome of the same cells are rarely measured together, which is especially consequential in cancer, where somatic mutations vary across clones and drive disease. We show that a single standard proteomics extraction tip can retain peptides on-tip after digestion while genomic DNA passes into the normally discarded flowthrough. Combined with Deep Visual Proteomics, flowthrough co-isolation enables cell-type-resolved spatial proteogenomics from archival FFPE tissue, demonstrated in melanoma.