Improving Cancer Gene Expression Data Quality through a TCGA Data-Driven Evaluation of Identifier Filtering.

Data quality is a recognized problem for high-throughput genomics platforms, as evinced by the proliferation of methods attempting to filter out lower quality data points. Different filtering methods lead to discordant results, raising the question, which methods are best? Astonishingly, little computational support is offered to analysts to decide which filtering methods are optimal for the research question at hand. To evaluate them, we begin with a pair of expression data sets, transcriptomic and proteomic, on the same samples.

A decision theory paradigm for evaluating identifier mapping and filtering methods using data integration.

Background: In bioinformatics, we pre-process raw data into a format ready for answering medical and biological questions. A key step in processing is labeling the measured features with the identities of the molecules purportedly assayed: "molecular identification" (MI). Biological meaning comes from identifying these molecular measurements correctly with actual molecular species.

Identifier mapping performance for integrating transcriptomics and proteomics experimental results.

Background: Studies integrating transcriptomic data with proteomic data can illuminate the proteome more clearly than either separately. Integromic studies can deepen understanding of the dynamic complex regulatory relationship between the transcriptome and the proteome. Integrating these data dictates a reliable mapping between the identifier nomenclature resultant from the two high-throughput platforms.

Gender differences in stimulated cytokine production following acute psychological stress.

Emerging evidence suggests that acute psychological stress modulates inflammatory competence; however, not all findings are consistent. Gender is one factor that may impact magnitude of response. To explore this possibility, we examined the effects of acute mental stress on lipopolysaccharide-induced production of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha among a relatively healthy sample of midlife men (n=28) and women (n=34).

Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients.

Background: Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes.

Methods: In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82).

Impact of TGFbeta1 gene polymorphisms on acute and chronic rejection in pediatric heart transplant allografts.

Background: The aim of this study was to assess the influence of IL-10 and TGFbeta1 gene polymorphisms on the development of acute rejection and coronary disease in pediatric heart transplant recipients.

Methods: Patients were classified as either Rejectors or Nonrejectors. Coronary artery disease (CAD) was diagnosed by angiography or on macroscopic examination.

Impact of ABCB1 (MDR1) haplotypes on tacrolimus dosing in adult lung transplant patients who are CYP3A5 *3/*3 non-expressors.

Background: The influence of ABCB1 (MDR1) polymorphisms on tacrolimus dosing has been questioned in previous studies with contradictory findings, possibly due to the association between CYP3A5 polymorphisms and tacrolimus dosing. The objective of this study was to assess the effect of ABCB1 haplotypes from 3 distinct polymorphic sites on the tacrolimus level/dose [L/D] in lung transplant patients limited to CYP3A5 *3/*3 non-expressors.

Method: A total of 91 lung transplant patients treated primarily with tacrolimus and prednisone were enrolled, and clinical information on drug dosing and blood levels was collected.

Impact of TGFbeta1 gene polymorphisms on late renal function in pediatric heart transplantation.

Late renal dysfunction may affect long-term outcome of nonrenal transplant recipients. We hypothesized that transforming growth factor beta1 (TGFbeta1) might play a role in the fibrogenic mechanisms leading to renal dysfunction. The aim was to determine whether TGFbeta1 gene polymorphisms are associated with renal outcome in pediatric heart recipients.

Interleukin-10 production genotype protects against acute persistent rejection after lung transplantation.

Background: Our previous studies demonstrated that cytokine gene polymorphisms are related to acute rejection in pediatric heart transplantation; a decreased tumor necrosis factor (TNF)-alpha production genotype combined with an increased or intermediate interleukin (IL)-10 production genotype was associated with the smallest incidence of acute rejection. The objective of this study was to determine whether cytokine genotypes TNF-alpha, IL-10, IL-6, interferon-gamma, and transforming growth factor beta were associated with acute persistent rejection after lung transplantation.

Methods: Cytokine genotyping was performed in 119 adult lung transplantation recipients who underwent surveillance transbronchial biopsies during their first year after transplantation.

Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism.

Tacrolimus is a potent immunosuppressive agent used in lung transplantation and is a substrate for both P-glycoprotein (P-gp, encoded by the gene MDR1) and cytochrome (CYP) P4503A. A previous study by the authors identified a correlation between the tacrolimus blood level per dose with CYP3A5 and MDR1 gene polymorphisms in pediatric heart transplant patients. The objective of this study was to confirm the influence of these polymorphisms on tacrolimus dosing in adult lung transplant patients.