Tandem mass tag proteomic and untargeted metabolomic profiling reveals altered serum and CSF biochemical datasets in iron deficient monkeys
Brian J Sandri,
Jonathan Kim,
Gabriele R. Lubach,
Eric F Lock,
Candace Guerrero,
LeeAnn Higgins,
Todd W Markowski,
Pamela J Kling,
Michael K Georgieff,
Christopher L. Coe,
Raghavendra B Rao
Affiliations
Brian J Sandri
Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA
Jonathan Kim
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Gabriele R. Lubach
Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, USA
Eric F Lock
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Candace Guerrero
Department of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
LeeAnn Higgins
Department of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
Todd W Markowski
Department of Biochemistry, Molecular Biology, & Biophysics, University of Minnesota, Minneapolis, Minnesota, USA
Pamela J Kling
Division of Neonatology, Department of Pediatrics, University of Wisconsin, Madison, WI, USA
Michael K Georgieff
Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA
Christopher L. Coe
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA
Raghavendra B Rao
Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Corresponding author's email address and Twitter handle
The effects of early-life iron deficiency anemia (IDA) extend past the blood and include both short- and long-term adverse effects on many tissues including the brain. Prior to IDA, iron deficiency (ID) can cause similar tissue effects, but a sensitive biomarker of iron-dependent brain health is lacking. To determine serum and CSF biomarkers of ID-induced metabolic dysfunction we performed proteomic and metabolomic analysis of serum and CSF at 4- and 6- months from a nonhuman primate model of infantile IDA. LC/MS/MS analyses identified a total of 227 metabolites and 205 proteins in serum. In CSF, we measured 210 metabolites and 1,560 proteins. Data were either processed from a Q-Exactive (Thermo Scientific, Waltham, MA) through Progenesis QI with accurate mass and retention time comparisons to a proprietary small molecule database and Metlin or with raw files imported directly from a Fusion Orbitrap (Thermo Scientific, Waltham, MA) through Sequest in Proteome Discoverer 2.4.0.305 (Thermo Scientific, Waltham, MA) with peptide matches through the latest Rhesus Macaque HMDB database. Metabolite and protein identifiers, p-values, and q-values were utilized for molecular pathway analysis with Ingenuity Pathways Analysis (IPA). We applied multiway distance weighted discrimination (DWD) to identify a weighted sum of the features (proteins or metabolites) that distinguish ID from IS at 4-months (pre-anemic period) and 6-months of age (anemic).
