Project description:This West Coast Metabolomics Center pilot and feasibility project was granted to Roel Ophoff (UC Los Angeles ) and Steve Horwath (UC Los Angeles ) . Major depressive disorder (MDD) is one of the most debilitating disorders in the United States with a 12-month prevalence of 6.7% in the adult population. The disorder affects millions of Americans daily and is a major health concern with enormous economic cost the society at large. Criteria for MDD diagnosis and treatment are based on various signs and symptoms not always fitting into strict diagnostic categories such as DSM-IV. Despite various known risk factors (such as family history, age, and gender), biological markers supporting diagnosis or prediction of MDD are unavailable. We have collected cerebrospinal fluid (CSF) and peripheral blood of more than 600 subjects from the general population. For each of the participants we also obtained biometric information as well as behavioral trait measures. One of the measures is the Beck Depression Inventory (BDI), a well-established questionnaire for measuring severity of depression. Based on the BDI, roughly 5% of participants suffer from severe depressive symptoms while most of these subjects are not under treatment or receiving any medication for depression
In the current investigation, untargeted analysis of primary metabolites was conducted on age and gender matched human cerebrospinal fluid (CSF) and plasma from subjects suffering with MDD ( n=50) and control subjects (n=50). Subjects were diagnosed as having MDD based on the Beck Depression Inventory.
The primary objectives of this study were to 1) identify metabolites which discriminate between subjects with and without depression symptoms in the CSF and plasma and 2) how changes correlate between CSF and plasma.
Project description:The human plasma proteome is clinically highly significant and has been studied extensively because it is thought that its molecular makeup provides a window into the health state of an individual. However, neither the quantitative variability of the plasma proteome nor the origins of the variation are known. To determine the relative contributions of heritability, environmental and longitudinal factors to plasma proteome variability we systematically decomposed the biological variance of 1904 peptides defining 342 unique plasma protein profiles from 232 plasma samples that were collected with 2-7 year intervals from monozygotic (MZ) and dizygotic (DZ) twins. The data were collected via SWATH mass spectrometry (SWATH-MS), an emerging technology characterized by high degree of reproducibility and quantitative accuracy. The data indicate abundance variability is an important feature for different proteins among population, that the abundances of about 20% of plasma protein are considerably heritable, and that the degrees of genetic control and aging effects vary across specific biological processes. Moreover, we identified 13 cis- SNPs significantly influencing the abundance level of specific plasma proteins. These results substantially extend the understanding of the impact of heritability on the human proteomic dynamics and therefore have implications for the effective design of plasma-based biomarker studies.
Project description:In order to determine whether dis-regulation of a genetic pathway could explain the increased apoptosis of parp-2-/- double positive thymocytes, the gene expression profiles in double positive thymocytes derived from wild-type and parp-2-/- mice were analysed using Affymetrix oligonucleotide chips (mouse genome 430 2.0).