Additional file 1 of Detecting antibody reactivities in Phage ImmunoPrecipitation Sequencing data

Additional file 1: Supplementary Materials

Demonstration of PCR products of <i>TIMP3</i> in gelelectrophoresis: MN 123 and MN 60 = patients with positive methylation status of <i>TIMP3</i>.

<p>MN 2 =  patient without methylation.</p

Univariate and multivariate Cox-regression analysis.

<p>Results for univariate and multivariate Cox regression models. For every variable, the estimated hazard ratio HR and its corresponding 95% confidence interval are given, as well as the p-value when testing HR = 1. P-values below 0.05 are marked with a star (*). The categorical variable WHO grade is treated as factor variable, thus HR refers to the comparison of WHO grade II and WHO grade III, respectively, to WHO grade I.</p

Figure 1

<p><b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094987#pone-0094987-g001" target="_blank">Figure 1a:</a></b> Two color FISH for chromosome 1p36/22q11 (Metasystems). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094987#pone-0094987-g001" target="_blank"><b>Figure 1b:</b></a> Probe map for dualcolor probe 1p36/9p21 and 22q11 (Metasystems).</p

Multivariate Cox-regression analysis with variable selection by AIC criterion.

<p>Results for multivariate Cox regression models with variable selection. For every variable, the estimated hazard ratio HR and its corresponding 95% confidence interval are given, as well as the p-value when testing HR = 1. The categorical variable WHO grade is treated as factor variable, thus HR refers to the comparison of WHO grade II and WHO grade III, respectively, to WHO grade I. The full model before variable selection included the additional variables age, p16, and 9p which were eliminated by stepwise backward selection with standard AIC (Akaike Information Criterion) as model selection criterion. All estimates and p-values in the table are close to the corresponding values before variable selection (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094987#pone-0094987-t003" target="_blank">Table 3</a>).</p

Kaplan-Meier survival curves for times to recurrence of meningioma patients; patients are split into 3 subgroups according to WHO grades.

<p>Kaplan-Meier survival curves for times to recurrence of meningioma patients; patients are split into 3 subgroups according to WHO grades.</p

Correlation between clinical variables and deletion of 1p36.

<p>Correlation between clinical variables and deletion of 1p36.</p

Kaplan-Meier survival curves for time of recurrences of meningioma patients; patients are split into 2 subgroups according to Deletion of 1p36.

<p>Kaplan-Meier survival curves for time of recurrences of meningioma patients; patients are split into 2 subgroups according to Deletion of 1p36.</p

Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death

Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances from sham-operated HYP and HF hearts were assessed by iTRAQ LC–MS/MS. Metabolites were quantified by LC–MS/MS or GC–MS. Transcriptome profiles were obtained using mRNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation, and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial procsses, were downregulated in HF but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, acylcarnitines were downregulated in HYP and fatty acids accumulated in HF. The correlation of transcript and protein changes in HF was weak (<i>R</i>² = 0.23), suggesting post-transcriptional gene regulation in HF. Proteome/metabolome integration indicated metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (<i>CPT1B</i>) as well as TCA cycle inhibition. On the basis of these findings, we present a model of cardiac decompensation involving impaired nuclear integration of Ca²⁺ and cyclic nucleotide signals that are coupled to mitochondrial metabolic and antioxidant defects through the CREB/PGC1α transcriptional axis

Quantitative Proteomic Analysis Reveals Similarities between Huntington’s Disease (HD) and Huntington’s Disease-Like 2 (HDL2) Human Brains

The pathogenesis of HD and HDL2, similar progressive neurodegenerative disorders caused by expansion mutations, remains incompletely understood. No systematic quantitative proteomics studies, assessing global changes in HD or HDL2 human brain, were reported. To address this deficit, we used a stable isotope labeling-based approach to quantify the changes in protein abundances in the cortex of 12 HD and 12 control cases and, separately, of 6 HDL2 and 6 control cases. The quality of the tissues was assessed to minimize variability due to post mortem autolysis. We applied a robust median sweep algorithm to quantify protein abundance and performed statistical inference using moderated test statistics. 1211 proteins showed statistically significant fold changes between HD and control tissues; the differences in selected proteins were verified by Western blotting. Differentially abundant proteins were enriched in cellular pathways previously implicated in HD, including Rho-mediated, actin cytoskeleton and integrin signaling, mitochondrial dysfunction, endocytosis, axonal guidance, DNA/RNA processing, and protein transport. The abundance of 717 proteins significantly differed between control and HDL2 brain. Comparative analysis of the disease-associated changes in the HD and HDL2 proteomes revealed that similar pathways were altered, suggesting the commonality of pathogenesis between the two disorders