Mapping interindividual dynamics of innate immune response at single-cell resolution
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Abstract
Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution.
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SciScore for 10.1101/2021.09.01.457774: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Cell culture and stimulation: Primary dermal fibroblast cells from the Human Induced Pluripotent Stem Cell Initiative (HipSci; http://www.hipsci.org/) were used. http://www.hipsci.org/suggested: (HipSci, RRID:SCR_003909)We converted the genome coordinate from hg19 to GRCh38 using CrossMap (version 0.5.2; http://crossmap.sourceforge.net/). CrossMapsuggested: (CrossMap, RRID:SCR_001173)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to …SciScore for 10.1101/2021.09.01.457774: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Cell culture and stimulation: Primary dermal fibroblast cells from the Human Induced Pluripotent Stem Cell Initiative (HipSci; http://www.hipsci.org/) were used. http://www.hipsci.org/suggested: (HipSci, RRID:SCR_003909)We converted the genome coordinate from hg19 to GRCh38 using CrossMap (version 0.5.2; http://crossmap.sourceforge.net/). CrossMapsuggested: (CrossMap, RRID:SCR_001173)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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