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immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse
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immgenT: A Comprehensive Reference of Convergent T-cell States in the Mouse

Ian Magill, Odhran Casey, Dania Mallah +60 more
February 2026
 ·
bioRxiv
 ·
DOI 
10.64898/2026.01.30.702892
94
%
Reproducible
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This paper passed independent validation.
QED's automated review checked the evidence supporting each claim, the statistical methods, and whether the results are reproducible from the data provided.

It ranks in the top 1% of preprints assessed in Immunology this quarter.
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Why this is interesting

This landmark atlas of ~800,000 mouse T cells spanning all organs overturns open-ended T-cell taxonomy, revealing 110 conserved states—a finite, structured landscape that gives immunology a universal, permanently reusable reference framework.

QED claims analysis

Summary

The immgenT consortium establishes a comprehensive molecular reference framework for mouse T cells by profiling ~800,000 cells across virtually all organs and disease states, revealing through AI-powered integration that T cell diversity occupies a finite landscape of 110 reproducible molecular states organized into eight lineages that are reused and redistributed across tissues and immune perturbations rather than generating context-specific identities, with this framework demonstrating near-saturation when validated against external datasets and providing superior cell identification compared to traditional marker- or signature-based approaches.

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Main Claim 1 –

immgenT profiles ~800,000 T cells across organs and diseases

Main Claim 2 –

totalVI integration harmonizes experiments and resolves eight T-cell lineages

Main Claim 3 –

110 consensus clusters capture T-cell heterogeneity and improve interpretability

Supporting evidence

  • 110 clusters preserve experiment structure and RNA/protein distinctness
  • Effector gene expression varies by cluster identity and context
  • Transcription factor specificity is limited across lineages and states
  • T-cell states arise from combinatorial reuse of shared gene programs
Main Claim 4 –

T-RBI maps external datasets, supporting near-saturation of T-cell states

Supporting evidence

  • Shared T-cell states are reused and redistributed across contexts
  • Reference mapping outperforms markers and gene signatures for identification

Abstract

The immgenT collaborative project generated a comprehensive molecular atlas of T cells spanning virtually all mouse organs and disease states, profiling ∼800,000 cells from 750 samples with RNA, 128-plex surface protein, and αβTCR sequence. Applying a deep generative model to joint RNA and protein data defined a finite landscape of T-cell states organized into eight lineages and 110 robust clusters, integrating identical cells from different contexts, and resolving prior nomenclatures. Analysis of effector molecules, transcription factors and modules showed that both immunological functions and regulatory programs are shared across cell states. This framework provides a stable, reusable reference, demonstrated by computationally integrating 16 external datasets from diverse biological contexts. A set of public web tools supports browsing of these data, allows mapping of any dataset onto the immgenT framework. These results propose a molecular classification of T cells organized around a set of shared states reused across immunological contexts.

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