Multimodal cell maps as a foundation for structural and functional genomics.

ABSTRACT: Human cells consist of a complex hierarchy of components, many of which remain unexplored^1,2. Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. Self-supervised multimodal data integration resolves 275 molecular assemblies spanning the range of 10^-8 to 10^-5 m, which we validate systematically using whole-cell size-exclusion chromatography and annotate using large language models³. We explore key applications in structural biology, yielding structures for 111 heterodimeric complexes and an expanded Rag-Ragulator assembly. The map assigns unexpected functions to 975 proteins, including roles for C18or

SUBMITTER: Schaffer LV 

PROVIDER: S-EPMC12137143 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature