This week, please read the paper titled as “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. 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 models. 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 C18orf21 in RNA processing and DPP9 in interferon signalling, and identifies assemblies with multiple localizations or cell type specificity. It decodes paediatric cancer genomes, identifying 21 recurrently mutated assemblies and implicating 102 validated new cancer proteins. The associated Cell Visualization Portal and Mapping Toolkit provide a reference platform for structural and functional cell biology.
Assignment
- Read the paper and use the Question Sheet which contains a set of questions designed to guide your reading and understanding.
- Fill out your question sheet and submit before the journal club.
- Be ready to discuss in the journal club.
Deadline: Submit your PDF before the journal club session.
Join the Journal Club
During the journal club, we will walk through the question sheet together. Everyone will be selected at random to answer one or more questions from the question sheet, and/or describe selected figures.
Note that it is mandatory to attend the journal club session, and participate in the discussion.