Friday, 25 January 2013 at 11:30am
Room 1400 Biomedical and Physical Sciences Bldg.
Refreshments at 11:15
Speaker: Mingyao Li, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine
Title: Translational Genomics Study in Evoked Human Inflammation
Abstract:
Inappropriate or sustained activation of innate immunity is a pathologic feature
of several common cardiometabolic disorders. Little is known, however, about
transcriptomic modulation during inflammatory stress in disease relevant human
tissues. We applied RNA sequencing (RNA-Seq) during low-dose experimental
endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner,
inflammatory tissue level transcriptome responses of relevance to complex
cardiometabolic diseases. We utilized adipose and blood samples from three
healthy individuals who underwent a standardized inpatient endotoxemia protocol.
Our comprehensive analysis revealed substantial, highly tissue-specific LPS
modulated changes in the expression of protein-coding genes and lincRNAs as well
as alternative splicing (AS). We also confirmed adipocytes and macrophages as
potential cell sources of selective LPS modulated lincRNAs and AS events. We
further defined disease relevance of a subset of findings in obese adipose
tissue and through interrogation of overlap with genome-wide association study
loci for cardiometabolic traits. Finally, we evaluated the relationship between
RNA-Seq depth and the ability to detect differentially expressed (DE) genes and
differential AS (DAS) events. Our results suggest that a much higher sequencing
depth is needed to reliably identify DAS events than for DE genes. Our findings
provide novel insights into tissue-level transcriptomic variations that are
relevant to common cardiometabolic diseases.