This SuperSeries is composed of the SubSeries listed below.
Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.
Disease, Disease stage
View SamplesMotivation: Sample source, procurement process, and other technical variations introduce batch effects into genomics data. Algorithms to remove these artifacts enhance differences between known biological covariates, but also carry potential concern of removing intra-group biological heterogeneity and thus any personalized genomic signatures. As a result, accurate identification of novel subtypes from batch corrected genomics data is challenging using standard algorithms designed to remove batch effects for class comparison analyses. Nor can batch effects be corrected reliably in future applications of genomics-based clinical tests, in which the biological groups are by definition unknown a priori.
Preserving biological heterogeneity with a permuted surrogate variable analysis for genomics batch correction.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAberrant activation of signaling pathways controlled in normal epithelial cells by the epidermal growth factor receptor (EGFR) has been linked to cetuximab (a monoclonal antibody against EGFR) resistance in head and neck squamous cell carcinoma (HNSCC). To infer relevant and specific pathway activation downstream of EGFR from gene expression in HNSCC, we generated gene expression signatures using immortalized keratinocytes (HaCaT) subjected to either ligand stimulation or pharmacological inhibition of the signaling intermediaries PI-3-Kinase and MEK or transfected with EGFR, RELA/p65, or HRASVal12. The gene expression patterns that distinguished the various HaCaT variants and conditions were inferred using the Markov chain Monte Carlo (MCMC) matrix factorization algorithm Coordinated Gene Activity in Pattern Sets (CoGAPS). This approach inferred gene expression signatures with greater relevance to cell signaling pathway activation than the expression signatures inferred with standard linear models. Furthermore, the pathway signature generated using HaCaT-HRASVal12 further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines. Our data suggest that the CoGAPS algorithm can generate gene expression signatures that are pertinent to downstream effects of receptor signaling pathway activation and potentially be useful in modeling resistance mechanisms to targeted therapies.
Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe aim of this study is to identify, for the first time, the genome-wide DNA methylation profiles of human articular chondrocytes from OA and healtly cartilage samples.
Genome-wide DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesSingle cell RNA sequencing using either an adapted Smart-seq2 protocol on Chx10-GFP (+) retinal progenitor cells; 10x Genomics Chromium Single Cell system across 10 timepoints of mouse retinal development to examine retinal progenitor cell heterogeneity across retinal development and global changes in gene expression from early retinal neuroepithelial cells through specification and differentiation of retinal cell types; 10X Genomics Chromium Single Cell on P14 Nfia/b/x het control or Nfia/b/x tCKO (Chx10-Cre-GFP) retinas Overall design: Examination of transcript expression within 120,840 cells across 10 developmental time-points (14 experiments) via 10x Genomics and 864 cells via an adapted Smart-Seq2 protocol; Characterization of Nfia/b/x mutant phenotypes using single-cell RNA-seq
Single-Cell RNA-Seq Analysis of Retinal Development Identifies NFI Factors as Regulating Mitotic Exit and Late-Born Cell Specification.
Specimen part, Cell line, Subject
View SamplesPrevious results from a genome scan in a F2 Iberian by Meishan intercross showed several chromosome regions associated with litter size traits. In order to identify candidate genes underlying these QTL we have performed an ovary gene expression analysis during pregnancy. F2 sows were ranked by their estimated breeding values for prolificacy, the six sows with higher EBV (HIGH prolificacy) and the six with lower EBV (LOW prolificacy) were selected. Samples were hybridized to Affymetrix porcine expression microarrays. The statistical analysis with a mixed-model approach identified 221 differentially expressed probes, representing 189 genes. These genes were functionally annotated in order to identify the genetic pathways overrepresented. Among the most represented functional groups the first one was immune system response activation against external stimulus. The second group was made up of genes which regulate the maternal homeostasis by complement and coagulation cascades. The last group was involved on lipid and fatty acid enzymes of metabolic processes, which participate in steroidogenesis pathway. In order to identify powerful candidate genes for prolificacy, the second approach of this study was merging microarray data with position information of QTL affecting litter size, previously detected in the same experimental cross. According to this, we have identified 27 differentially expressed genes co-localized with QTL for litter size traits, which fulfill the biological, positional and functional criteria.
Differential gene expression in ovaries of pregnant pigs with high and low prolificacy levels and identification of candidate genes for litter size.
Specimen part
View SamplesPatients with oncogene driven tumors are currently treated with targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors. The inhibited oncogenic pathway often interacts with other signaling pathways and alters predicted therapeutic response. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates pervasive molecular alterations to EGFR, MAPK, and PI3K signaling in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to infer the complex pathway interactions that result from EGFR inhibitor use in cancer cells that contain these these common EGFR network genetic alterations. To do this, we modified the HaCaT keratinocyte cell line model of premalignancy to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background. We then measured gene expression after treating modified HaCaT cells with three EGFR targeted agents (gefitinib, afatinib, and cetuximab) for 24 hours.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Cell line, Treatment
View SamplesTo determine the expression AP2-alpha target genes, global gene expression of 7 HNSCC cell lines with and without cetuximab treatment (100 nM, 24 hrs) and the HaCaT keratinocyte cell line was performed.
CoGAPS matrix factorization algorithm identifies transcriptional changes in AP-2alpha target genes in feedback from therapeutic inhibition of the EGFR network.
Specimen part, Cell line
View SamplesTo determine the differential expression of KRAS-variant HNSCC (head and neck squamous cell carcinoma) cell lines.
A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
Specimen part, Cell line
View Samples