Multimodal cell maps as a foundation for structural and functional genomics
Ontology highlight
ABSTRACT: Human cells contain a complex hierarchy of components, many of which remain uncharted. Here we broadly identify subcellular components across the 10–9–10–5 meter range, via self-supervised fusion of immunofluorescence images and biophysical interactions measured for >5100 proteins in U2-OS human cells. This global multi-scale map resolves 275 molecular assemblies, which we systematically validate by whole-cell size-exclusion chromatography and annotate using large language models. We explore key applications in driving 3D structural biology, yielding novel structures for 79 heterodimeric complexes and an expanded 10-protein Rag-Ragulator assembly. The map assigns functions to 46 understudied proteins, including a role for C18orf21 in RNA processing. It functionally decodes cancer genomes, identifying 21 recurrently mutated assemblies including cell junctions, SWI/SNF complexes, and an NCOR complex, encompassing 102 cancer driver proteins that validate by transposon mutagenesis. The Multiscale Integrated Cell portal provides a queryable reference platform for structural and functional cell biology.
INSTRUMENT(S): Bruker Daltonics timsTOF series
ORGANISM(S): Homo Sapiens (human)
SUBMITTER: Jenny Moon
LAB HEAD: Leonard J. Foster
PROVIDER: PXD052362 | Pride | 2025-01-08
REPOSITORIES: pride
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