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Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing

View ORCID ProfileCaleb M. Radens, Davia Blake, Paul Jewell, View ORCID ProfileYoseph Barash, Kristen W. Lynch
doi: https://doi.org/10.1101/727362
Caleb M. Radens
1Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104
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  • ORCID record for Caleb M. Radens
Davia Blake
2Immunology Graduate Groups, University of Pennsylvania, Philadelphia, PA 19104
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Paul Jewell
4Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
5Department of Computer Science, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104
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Yoseph Barash
1Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104
4Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
5Department of Computer Science, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104
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  • For correspondence: klync@pennmedicine.upenn.edu yosephb@seas.upenn.edu
Kristen W. Lynch
1Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104
2Immunology Graduate Groups, University of Pennsylvania, Philadelphia, PA 19104
3Departments of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104
4Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
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  • For correspondence: klync@pennmedicine.upenn.edu yosephb@seas.upenn.edu
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Summary

Distinct T cell subtypes are typically defined by the expression of distinct gene repertoires. However, there is variability between studies regarding the markers used to define each T cell subtype. Moreover, previous analysis of gene expression in T cell subsets has largely focused on gene expression rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-Seq studies of human Th1, Th2, Th17 and/or Treg cells to identify transcriptomic features that correlate consistently with subtype. We find that known master-regulators are consistently enriched in the appropriate subtype, however, cytokines and other genes often used as markers are more variable. Importantly, we also identify previously unknown transcriptomic markers that consistently differentiate between subsets, including a few Treg-specific splicing patterns. Together this work highlights the heterogeneity in gene expression between isolates of the same subtype, but also suggests additional markers that can be used to define functional groupings.

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  • ↵# Lead Contact (K.W.L.: klync{at}pennmedicine.upenn.edu)

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 09, 2019.
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Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing
Caleb M. Radens, Davia Blake, Paul Jewell, Yoseph Barash, Kristen W. Lynch
bioRxiv 727362; doi: https://doi.org/10.1101/727362
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Meta-Analysis of Transcriptomic Variation in T cell Populations Reveals Novel Signatures of Gene Expression and Splicing
Caleb M. Radens, Davia Blake, Paul Jewell, Yoseph Barash, Kristen W. Lynch
bioRxiv 727362; doi: https://doi.org/10.1101/727362

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