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Age, Sex, and Genetics Influence the Abundance of Infiltrating Immune Cells in Human Tissues

Andrew R. Marderstein, Manik Uppal, Akanksha Verma, Bhavneet Bhinder, Jason Mezey, Andrew G. Clark, Olivier Elemento
doi: https://doi.org/10.1101/614305
Andrew R. Marderstein
1Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
3Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
4Department of Computational Biology, Cornell University, Ithaca, NY, USA
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Manik Uppal
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
3Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
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Akanksha Verma
1Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
3Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
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Bhavneet Bhinder
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
3Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
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Jason Mezey
1Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
4Department of Computational Biology, Cornell University, Ithaca, NY, USA
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Andrew G. Clark
1Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA
4Department of Computational Biology, Cornell University, Ithaca, NY, USA
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  • For correspondence: ac347@cornell.edu ole2001@med.cornell.edu
Olivier Elemento
1Tri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA
2Institute of Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
3Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA
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  • For correspondence: ac347@cornell.edu ole2001@med.cornell.edu
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Abstract

Despite infiltrating immune cells playing an essential role in human disease and the patient response to treatment, the central mechanisms influencing variability in infiltration patterns are unclear. Using bulk RNA-seq data from 53 GTEx tissues, we applied cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We first performed a differential expression analysis of inflamed versus non-inflamed samples to identify essential pathways and regulators of infiltration. Next, we found 21 of 73 infiltration-related phenotypes to be associated with either age or sex (FDR < 0.1). Through our genetic analysis, we discovered 13 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10−8), with a significant enrichment of tissue-specific expression quantitative trait loci in suggested iQTLs (P < 10−5). We highlight an association between neutrophil content in lung tissue and a variant near the CUX1 transcription factor gene (P = 9.7 × 10−11), which has been previously linked to neutrophil infiltration, inflammatory mechanisms, and the regulation of several immune response genes. Together, our results identify key factors influencing inter-individual variability of specific tissue infiltration patterns, which could provide insights on therapeutic targets for shifting infiltration profiles to a more favorable one.

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Posted April 19, 2019.
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Age, Sex, and Genetics Influence the Abundance of Infiltrating Immune Cells in Human Tissues
Andrew R. Marderstein, Manik Uppal, Akanksha Verma, Bhavneet Bhinder, Jason Mezey, Andrew G. Clark, Olivier Elemento
bioRxiv 614305; doi: https://doi.org/10.1101/614305
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Age, Sex, and Genetics Influence the Abundance of Infiltrating Immune Cells in Human Tissues
Andrew R. Marderstein, Manik Uppal, Akanksha Verma, Bhavneet Bhinder, Jason Mezey, Andrew G. Clark, Olivier Elemento
bioRxiv 614305; doi: https://doi.org/10.1101/614305

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