Towards Biomarkers for Improving Disease Resistance in Pigs
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Introduction
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Area under Log Curve of shed Salmonella: A measure of disease spread potential
Finding markers and classifiers for improving pork safety
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Microarrays: measuring thousands of RNAs at once
A “Gene Expression Signature” that predicts a biological outcome- like cancer survival
“MammaPrint” classifier - a diagnostic test for breast cancer prognosis
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Shedding phenotype: AULC in 40 challenged pigs
Studying immune response to pathogen
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Finding important response pathways: InnateDB analysis
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Innate DB: pathways over-represented in genes DE post-infection in PS animals
Sub-Network Enrichment Analysis- looking for regulators of major portions of the response
SNEA Identifies Major Regulators of Genes in DE List
Some regulators are themselves DE
Some regulators are themselves DE
Some regulators are themselves DE
Some regulators are themselves DE
Response to Sal using Q-PCR: miR-155 ? miR-155 targets ?
Network of integrated pathways affected by Salmonella measured in whole blood RNA
SNEA Identifies Major Regulators of Genes in DE List
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Interferon gamma (IFNG)
Using immune response to find tools to manage disease
Can you use blood RNA response to predict shedding?
Measurement of circulating IFN gamma levels in a second challenge confirms previous correlation
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Are IFN gamma levels a major cause of gene expression patterns?
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Are IFN gamma levels a major cause of gene expression patterns?
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In vivo and in vitro treatments
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Studying immune response to pathogen versus expression patterns prior to infection
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Conclusions
Future work- other relevant projects
NF-?B Inhibitor: SC-514
Transcriptional Mechanisms in Porcine Endotoxin response- Genes dependent on NF?B signaling
Hierarchical clustering and annotation
Future work- new SCID pig discovery
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Questions?
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CC
We were able to verify this observation in pig
blood in a second Salmonella challenge
that I will describe in detail later. Both the
correlation of individual
IFNgamma and sig diff between shedding
extremes was confirmed. So we are
interested in taking this further, and…
Ok, just say the latter half
Ok, just say the latter half