Project description:This study is to compare the mRNA expression differences between atherosclerosis and non-atherosclerosis samples from female peripheral blood. The possible effects of races are also considered.
Project description:Expression profiling holds great promise for genetics because of its ability to measure thousands of genes quantitatively. Although transcriptomes have recently been used to perform epistasis analyses for pathway reconstruction, there has not been a systematic effort to understand how expression profiles will vary among distinct mutants of the same gene. Here, we study an allelic series in C. elegans consisting of one wild type and two mutant alleles of mdt-12, a highly pleiotropic gene whose gene product is a subunit of Mediator complex, which is essential for transcriptional regulation in eukaryotes. We developed a false hit analysis to identify which populations of genes commonly differentially expressed with respect to the wild type are likely the result of statistical artifact. We concluded that expression perturbations caused by these alleles split into four distinct modules called phenotypic classes. To understand the dominance relationship between the two mutant alleles, we developed a dominance analysis for transcriptional data. Dominance analysis of these phenotypic classes support a model where mdt-12 has multiple functional units that function independently to target the Mediator complex to specific genetic loci.
Project description:A major challenge to the study of tumor DNA copy number (CN) in clinical specimens is the lack of appropriate fresh frozen samples and thus a dependence on Formalin-Fixed Paraffin Embedded (FFPE) banked samples, which typically have more extensive clinical follow up information. However, on most high density CN platforms, DNA from FFPE tissues generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from DNA isolated from cell lines and frozen tumor samples. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess FFPE samples. In this study, we successfully applied MIP technology with a panel of 50,000 markers to CN determination in FFPE samples. Using an input of 37 ng genomic DNA, we demonstrated high quality CN data with MIP technology from 93 FFPE samples from seven diverse collections. We found that the performance of FFPE DNA for CN determination was comparable to that of DNA obtained from matched frozen tumor, with only a modest loss in performance of DNA.
Project description:: A major challenge to the study of tumor DNA copy number (CN) in clinical specimens is the lack of appropriate fresh frozen samples and thus a dependence on Formalin-Fixed Paraffin Embedded (FFPE) banked samples, which typically have more extensive clinical follow up information. However, on most high density CN platforms, DNA from FFPE tissues generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from DNA isolated from cell lines and frozen tumor samples. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess FFPE samples. In this study, we successfully applied MIP technology with a panel of 50,000 markers to CN determination in FFPE samples. Using an input of 37 ng genomic DNA, we demonstrated high quali ty CN data with MIP technology from 93 FFPE samples from seven diverse collections. We found that the performance of FFPE DNA for CN determination was comparable to that of DNA obtained from matched frozen tumor, with only a modest loss in performance of DNA.
Project description:A major challenge to the study of tumor DNA copy number (CN) in clinical specimens is the lack of appropriate fresh frozen samples and thus a dependence on Formalin-Fixed Paraffin Embedded (FFPE) banked samples, which typically have more extensive clinical follow up information. However, on most high density CN platforms, DNA from FFPE tissues generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from DNA isolated from cell lines and frozen tumor samples. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess FFPE samples. In this study, we successfully applied MIP technology with a panel of 50,000 markers to CN determination in FFPE samples. Using an input of 37 ng genomic DNA, we demonstrated high quali ty CN data with MIP technology from 93 FFPE samples from seven diverse collections. We found that the performance of FFPE DNA for CN determination was comparable to that of DNA obtained from matched frozen tumor, with only a modest loss in performance of DNA.
Project description:This SuperSeries is composed of the following subset Series: GSE14740: FFPE study using MIP copy number platform - kidney GSE14741: FFPE study using MIP copy number platform - bladder/colorectal/kidney/liver GSE14742: FFPE study using MIP copy number platform - colorectal GSE14743: FFPE study using MIP copy number platform - breast cancer I GSE14744: FFPE study using MIP copy number platform - breast cancer II GSE14745: FFPE study using MIP copy number platform - liver Refer to individual Series, GSE14856_quartets.txt contains list of matched samples
Project description:The robust transcriptional plasticity of liver mediated through xenobiotic receptors underlies its ability to respond rapidly and effectively to diverse chemical stressors. Thus, drug-induced gene expression changes in liver serve not only as biomarkers of liver injury, but also as mechanistic sentinels of adaptation in metabolism, detoxification and tissue protection from chemicals. Modern RNA sequencing methods offer an unmatched opportunity to quantitatively monitor these processes in parallel and to contextualize the spectrum of dose-dependent stress, adaptation, protection and injury responses induced in liver by drug treatments. Using this approach, we profiled the transcriptional changes in rat liver following daily oral administration of 95 different compounds, many of which are known to be associated with clinical risk for drug induced liver injury (DILI) by diverse mechanisms.