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.
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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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Inspect source passages
Can topology find real cell types across scales?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
HiDeF analyzed mRNA profiles of 100,605 mouse single cells.
mRNA expression profiles of 100,605 single cells gathered across the organs and tissues of mice
65% (89/136) of reference cell types had Jaccard >0.5 overlap with a HiDeF community.
65% (89/136) having a highly overlapping community (Jaccard index > 0.5) in the HiDeF hierarchy
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.
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