Bioinformatic analyses in early host response to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) reveals pathway differences between pigs with alternate genotypes for a major host response QTL
Bibliographic record
Abstract
BACKGROUND: A region on Sus scrofa chromosome 4 (SSC4) surrounding single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) has been reported to be strongly associated with both weight gain and serum viremia in pigs after infection with PRRS virus (PRRSV). A proposed causal mutation in the guanylate binding protein 5 gene (GBP5) is predicted to truncate the encoded protein. To investigate transcriptional differences between WUR genotypes in early host response to PRRSV infection, an RNA-seq experiment was performed on globin depleted whole blood RNA collected on 0, 4, 7, 10 and 14 days post-infection (dpi) from eight littermate pairs with one AB (favorable) and one AA (unfavorable) WUR genotype animal per litter. RESULTS: Gene Ontology (GO) enrichment analysis of transcripts that were differentially expressed (DE) between dpi across both genotypes revealed an inflammatory response for all dpi when compared to day 0. However, at the early time points of 4 and 7dpi, several GO terms had higher enrichment scores compared to later dpi, including inflammatory response (p < 10(-7)), specifically regulation of NFkappaB (p < 0.01), cytokine, and chemokine activity (p < 0.01). At 10 and 14dpi, GO term enrichment indicated a switch to DNA damage response, cell cycle checkpoints, and DNA replication. Few transcripts were DE between WUR genotypes on individual dpi or averaged over all dpi, and little enrichment of any GO term was found. However, there were differences in expression patterns over time between AA and AB animals, which was confirmed by genotype-specific expression patterns of several modules that were identified in weighted gene co-expression network analyses (WGCNA). Minor differences between AA and AB animals were observed in immune response and DNA damage response (p = 0.64 and p = 0.11, respectively), but a significant effect between genotypes pointed to a difference in ion transport/homeostasis and the participation of G-coupled protein receptors (p = 8e-4), which was reinforced by results from regulatory and phenotypic impact factor analyses between genotypes. CONCLUSION: We propose these pathway differences between WUR genotypes are the result of the inability of the truncated GBP5 of the AA genotyped pigs to inhibit viral entry and replication as quickly as the intact GBP5 protein of the AB genotyped pigs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".