Intersection of population variation and autoimmunity genetics in human T cell activation
Open accessAbstract
Response to pathogens is in the genes: T cells are important in mounting immune responses to a host of pathogens, and they have also been implicated in autoimmune disease. By examining the variability in gene expression in stimulated T cells over time from a multi-ethnic cohort of healthy humans, Ye et al. identified specific genetic polymorphisms that explain differences among individuals in response to pathogens. Furthermore, a candidate gene approach led to the identification of a single-nucleotide polymorphism that controls the response of the autoimmune-associated IL2RA gene. This study helps us understand the degree to which immune responses are driven by the environment or by an individual's physiological or genetic factors. Science , this issue 10.1126/science.1254665
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Simultaneously demultiplexing and detecting doublets from more than two individuals has not been possible.
“While strategies to demultiplex cells from different species1, 10, 17 or host and graft samples17 have been reported, simultaneously demultiplexing and detecting doublets from more than two individuals has not been possible.”
From Multiplexed droplet single-cell RNA-sequencing using natural genetic variation (2018) · cites this paper as [17]
The section ‘An experimental and analytic strategy to dissect inter-individual variation’ describes measuring T-cell transcripts from multiple donors, but does not address demultiplexing cells or detecting doublets. Searches for those methods and for the claimed limit of two individuals found no relevant passage in our copy. (LLM, conf=0.76)
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“Inspired by models and algorithms developed for detecting contamination in DNA sequencing18, demuxlet is fast, accurate, scalable, and compatible with standard input formats17, 19, 20.”
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The section “An experimental and analytic strategy to dissect inter-individual variation” describes Nanostring measurements and eQTL analysis, not demuxlet. Searches for demuxlet’s speed, accuracy, scalability, input-format compatibility, and single-cell demultiplexing found no passage addressing those properties in our copy. (LLM, conf=0.77)
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- Authors
- Ye, C. J., Feng, T., Kwon, H.-K., Raj, T., Wilson, M. T., Asinovski, N., McCabe, C., Lee, M. H., Frohlich, I., Paik, H.-I., Zaitlen, N., Hacohen, N., Stranger, B., De Jager, P., Mathis, D., Regev, A., & Benoist, C.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA.
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- University of Chicago (US)
- Corresponding author
- Regev, Aviv
- Benoist, Christophe
- ORCID
- Venue
- Science
- Published
- 2014-09-12
- Volume
- 345
- Issue
- 6202
- Pages
- 1254665-1254665
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4751028
- OpenAlex
- W2057406395
- Cited by
- 236
- References
- 55
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 16 · 2023: 16 · 2022: 20 · 2021: 17 · 2020: 24 · 2019: 29 · 2018: 26 · 2017: 17 · 2016: 25 · 2015: 30 · 2014: 2 · 2013: 1
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (F32AG043267)
- National Institute of General Medical Sciences (RC2GM093080)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- T cell activation, CD4+ T cells, Th17 cells, autoimmune disease genetics, gene expression, ancestry differences, cis-eQTL, fine mapping, enhancer regulation, IL2RA, regulatory T cells, autoimmune disease
- MeSH terms
- Gene Expression Regulation, Multigene Family, Humans, Lymphocyte Activation, Genetic Variation, CD4-Positive T-Lymphocytes, Autoimmunity, Cytokines, Quantitative Trait Loci, Black People, White People, Asian People, Genome-Wide Association Study, Th17 Cells
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