P6034 Associations between cis-expression quantitative trait loci markers and host response to Porcine reproductive and respiratory syndrome virus infection
Bibliographic record
Abstract
Porcine reproductive and respiratory syndrome (PRRS) is economically the most important disease of pigs with annual U.S. losses of $664 M. Understanding transcriptional responses to viral infection should reveal mechanisms to help control PRRS. The PRRS Host Genetics Consortium (PHGC) was established to combine efforts of scientists from university, government, commercial pig genetics and animal health companies to assess the role of genetics in determining pig resistance or susceptibility to PRRS virus (PRRSV) infection, pathology, and growth effects. The PHGC used a nursery pig PRRSV infection model with deep sampling for phenotypic analyses, extensive genotyping (60K SNPchip) and a shared database (www.animalgenome.org/lunney/, verified 26 May 2016). We probed the blood transcriptome of PHGC pigs using RNaseq to address disease resistance mechanisms and the underlying genetic architecture of gene expression in response to PRRSV infection. We integrated genome-wide genotype, gene expression, viremia, and weight gain data to identify differential expression and genetic variation controlling expression levels and association to phenotypes in response to Type 2 PRRSV infection. RNA was prepared from Tempus tube preserved peripheral blood samples collected just before experimental challenge (Day 0) and at 4, 7, 10, and 14 d postinfection from 44 pigs, and globin RNA depleted before library production. RNA-seq analysis revealed 6430 differentially expressed genes after infection. We mapped genetic variation that is associated with interindividual differences in expression at each day and found evidence of cis-acting expression quantitative trait loci (cis-eQTL) for 1201 genes. Associations between cis-eQTL markers and phenotypes using 383 pigs indicated host genotype-dependent reduced expression of four genes, including GBP5 as expected from our earlier mapping results. These cis-eQTLs contribute to differences in viremia levels or weight gain in response to PRRSV infection. We also showed evidence of allele-specific expression for those four genes. This study expands our understanding of disease control mechanisms and provides potential new diagnostic tools for pig breeders. Further studies are needed to define the causal mutations that regulate expression of these candidate susceptibility genes and test how changes in expression of these genes can directly affect the traits. This work was funded by Genome Canada, Genome Alberta, Alberta Livestock and Meat Agency, PigGen Canada, and USDA ARS.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".