Gene expression
Can topology find real cell types across scales?
Open access · cc by · source: Europe PMC
HiDeF finds structures that persist across resolutions: it recovered 89/136 mouse cell types (Jaccard >0.5), proposed 273 cell-type communities from 100,605 cells, and linked SARS-CoV-2 Nsp13 to TLE/WNT proteins.
Study at a glance
- Design
- Computational / modelling — HiDeF persistent-homology community detection on Tabula Muris scRNA-seq and protein-interaction networks, including SARS-CoV-2–human BioPlex
- N
- N=100605 · 100,605 mouse single cells; 136 reference cell types; 273 HiDeF communities; 332 SARS-CoV-2-interacting human proteins expanded to 1,948 proteins
- Population
- Tabula Muris mouse single-cell transcriptomes and human/yeast protein-protein interaction networks (BioPlex/STRING), including SARS-CoV-2 host proteins
- Outcome
- Recovery of reference cell types (Jaccard/F1) and persistent multiscale protein communities, including a TLE/WNT community targeted by viral Nsp13
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Key findings
HiDeF matched reference types better than comparators (65% with Jaccard >0.5), yielded 273 putative mouse cell types, and among 251 persistent SARS-CoV-2-proximal communities highlighted TLE proteins that inhibit WNT—suggesting viral hijacking of that pathway.
Methodology
Applied persistent-homology community detection (HiDeF) to Tabula Muris cell-similarity networks and to protein interactomes, comparing recovery of 136 reference cell types against TooManyCells and Conos, then clustered a BioPlex neighborhood of 332 SARS-CoV-2 host proteins.
Limitations
Better overlap with existing annotations is not proof of new biology; SARS-CoV-2 WNT hijacking is a network inference, not a virology experiment, and mouse atlas labels still constrain what ‘new cell types’ mean.
How this study connects
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