PSXIV-17 Gene co-expression network analysis identifies important modules and genes for cow’s response to Mycobacterium avium ssp. paratuberculosis infection in the small intestine.
Bibliographic record
Abstract
Johne’s disease (JD), caused by Mycobacterium avium ssp. paratuberculosis (MAP), is an important economic disease of dairy cows. However, little is known about the mechanisms underlying JD development. Here, we combined weighted gene coexpression network (WGCNA) and enrichment analyses to identify important genes, pathways and transcription factors (TF)s regulating MAP infection in cow’s small intestine. Total RNA from ileum, ileum lymph node, mid-jejunum and mid-jejunum lymph node tissues from five MAP-infected and five healthy cows was subjected to RNA-sequencing (Illumina HiSeq2500) followed by bioinformatics processing (standard softwares). Raw read count was normalized with Deseq2 and the co-expression patterns of 5000 most highly variable genes were identified using WGCNA. Enrichment analyses were accomplished with EnrichR. Nine co-expressed gene modules were identified. Two of them, CYAN and DARKRED, were correlated to JD status (p<0.05). CTSH and MERTK were the hub genes (have the highest level of inter-connectivity with other genes in the module) of CYAN (401 genes) and DARKRED (110 genes) modules, respectively. CTSH is important for degradation of lysosomal proteins and MERTK is involved in phagocytosis of apoptotic cells (efferocytosis), which are important processes during MAP infection. Neutrophil degranulation and lysosome pathways were the most enriched (p.FDR≤3.04e-26) biological process and KEGG pathway for CYAN genes suggesting involvement in the maintenance of host integrity by MAP infection. Phagocytosis and Staphylococcus aureus infection were the most enriched (p.FDR≤0.003) GO and KEGG pathway for DARKRED genes suggesting participation in phagocytosis process and disease related pathways. The most significantly enriched TFs for CYAN and DARKRED modules were SPI1 (involved in activation of gene expression during myeloid/B-lymphoid cell development) and EP300 (involved in transcriptional regulation of genes via chromatin remodeling), respectively. This study highlighted important genes and networks involved in the host response to MAP infection in the small intestine which furthers understanding of the biology of JD.
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".