Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics

This
study uses advanced proteogenomic approaches in a nonmodel
organism to elucidate cardioprotective mechanisms used during mammalian
hibernation. Mammalian hibernation is characterized by drastic reductions
in body temperature, heart rate, metabolism, and oxygen consumption.
These changes pose significant challenges to the physiology of hibernators,
especially for the heart, which maintains function throughout the
extreme conditions, resembling ischemia and reperfusion. To identify
novel cardioadaptive strategies, we merged large-scale RNA-seq data
with large-scale iTRAQ-based proteomic data in heart tissue from 13-lined
ground squirrels (Ictidomys tridecemlineatus) throughout
the circannual cycle. Protein identification and data analysis were
run through Galaxy-P, a new multiomic data analysis platform enabling
effective integration of RNA-seq and MS/MS proteomic data. Galaxy-P
uses flexible, modular workflows that combine customized sequence
database searching and iTRAQ quantification to identify novel ground
squirrel-specific protein sequences and provide insight into molecular
mechanisms of hibernation. This study allowed for the quantification
of 2007 identified cardiac proteins, including over 350 peptide sequences
derived from previously uncharacterized protein products. Identification
of these peptides allows for improved genomic annotation of this nonmodel
organism, as well as identification of potential splice variants,
mutations, and genome reorganizations that provides insights into
novel cardioprotective mechanisms used during hibernation.