The MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sex, Age, Specimen part, Race, Compound
View SamplesThe multiple myeloma (MM) data set (endpoints F, G, H, and I) was contributed by the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences (UAMS, Little Rock, AR, USA). Gene expression profiling of highly purified bone marrow plasma cells was performed in newly diagnosed patients with MM. The training set consisted of 340 cases enrolled on total therapy 2 (TT2) and the validation set comprised 214 patients enrolled in total therapy 3 (TT3). Plasma cells were enriched by anti-CD138 immunomagnetic bead selection of mononuclear cell fractions of bone marrow aspirates in a central laboratory. All samples applied to the microarray contained more than 85% plasma cells as determined by 2-color flow cytometry (CD38+ and CD45-/dim) performed after selection. Dichotomized overall survival (OS) and eventfree survival (EFS) were determined based on a two-year milestone cutoff. A gene expression model of high-risk multiple myeloma was developed and validated by the data provider and later on validated in three additional independent data sets.
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sex, Age
View SamplesThe NIEHS data set (endpoint C) was provided by the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (Research Triangle Park, NC, USA). The study objective was to use microarray gene expression data acquired from the liver of rats exposed to hepatotoxicants to build classifiers for prediction of liver necrosis. The gene expression compendium data set was collected from 418 rats exposed to one of eight compounds (1,2-dichlorobenzene, 1,4-dichlorobenzene, bromobenzene, monocrotaline, N-nitrosomorpholine, thioacetamide, galactosamine, and diquat dibromide). All eight compounds were studied using standardized procedures, i.e. a common array platform (Affymetrix Rat 230 2.0 microarray), experimental procedures and data retrieving and analysis processes.
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sex, Specimen part, Compound
View SamplesThe human breast cancer (BR) data set (endpoints D and E) was contributed by the University of Texas M. D. Anderson Cancer Center (MDACC, Houston, TX, USA). Gene expression data from 230 stage I-III breast cancers were generated from fine needle aspiration specimens of newly diagnosed breast cancers before any therapy. The biopsy specimens were collected sequentially during a prospective pharmacogenomic marker discovery study between 2000 and 2008. These specimens represent 70-90% pure neoplastic cells with minimal stromal contamination. Patients received 6 months of preoperative (neoadjuvant) chemotherapy including paclitaxel, 5-fluorouracil, cyclophosphamide and doxorubicin followed by surgical resection of the cancer. Response to preoperative chemotherapy was categorized as a pathological complete response (pCR = no residual invasive cancer in the breast or lymph nodes) or residual invasive cancer (RD), and used as endpoint D for prediction. Endpoint E is the clinical estrogen-receptor status as established by immunohistochemistry. RNA extraction and gene expression profiling were performed in multiple batches over time using Affymetrix U133A microarrays. Genomic analysis of a subset of this sequentially accrued patient population were reported previously. For each endpoint, the first 130 cases were used as a training set and the next 100 cases were used as an independent validation set.
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Age, Specimen part, Race
View SamplesThe Hamner data set (endpoint A) was provided by The Hamner Institutes for Health Sciences (Research Triangle Park, NC, USA). The study objective was to apply microarray gene expression data from the lung of female B6C3F1 mice exposed to a 13-week treatment of chemicals to predict increased lung tumor incidence in the 2-year rodent cancer bioassays of the National Toxicology Program. If successful, the results may form the basis of a more efficient and economical approach for evaluating the carcinogenic activity of chemicals. Microarray analysis was performed using Affymetrix Mouse Genome 430 2.0 arrays on three to four mice per treatment group, and a total of 70 mice were analyzed and used as the MAQC-II's training set (GEO Series GSE6116). Additional data from another set of 88 mice were collected later and provided as the MAQC-II's external validation set (this Series). The training dataset had already been deposited in GEO by its provider and its accession number is GSE6116.
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Specimen part, Compound
View SamplesRecently a genome of Russian individual (somatic DNA from blood) was sequenced (Skryabin et al. 2009). That study was continued to find a linkage between genetic differences in parental alleles and bias in biallelic expression of genes.
Individual genome sequencing identified a novel enhancer element in exon 7 of the CSFR1 gene by shift of expressed allele ratios.
No sample metadata fields
View SamplesGene expression profiles of WT (wild type) and CCM-1, -2, and -3 KD (knockdown of krit1, ccm2 and pdcd10 genes) cells under 2D (Matrigel-coated plastic) and 3D (Matrigel) conditions. Deep sequencing of RNA was performed for cells at the initial (2hrs) and later (6hrs) stages of EC tubule formation. Overall design: Comparative analysis of gene expression of healthy and diseased cells in the tube formation assay
Biomechanics of Endothelial Tubule Formation Differentially Modulated by Cerebral Cavernous Malformation Proteins.
Cell line, Subject
View SamplesThe differentiated state of somatic cells provides barriers for the efficient derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. This revealed that inhibition of TGF together with activation of Wnt signaling in presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after one week of reprogramming factor expression. In contrast, hepatic progenitors and blood progenitors predominantly required only TGF inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner. We further demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF/MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Together, our observations define novel cell type-specific requirements for the rapid and synchronous reprogramming of somatic cells.
Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming.
Specimen part, Time
View SamplesCharacterization of the transcriptome of normal and abnormal embryos. Overall design: Gene expression profiling of every mono and trisomy.
Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profiles.
Specimen part, Subject
View SamplesThe regional specificity and timing of gene activation following chemotherapy, and how this relates to subsequent mucositis development is currently unknown. The aim of the study was therefore to determine the early time course of gene expression changes along the gastrointestinal tract (GIT) of the DA rat following irinotecan treatment, so as to provide an insight into the genetic component of mucositis.
Gene expression analysis of multiple gastrointestinal regions reveals activation of common cell regulatory pathways following cytotoxic chemotherapy.
Sex, Age
View Samples