Background: Previous studies comparing quantitative proteomics and microarray data have generally found poor correspondence between the two. We hypothesised that this might in part be because the different assays were targeting different parts of the expressed genome and might therefore be subjected to confounding effects from processes such as alternative splicing. Results: Using a genome database as a platform for integration, we combined quantitative protein mass spectrometry with Affymetrix Exon array data at the level of individual exons. We found significantly higher degrees of correlation than have been previously observed (r=0.808). The study was performed using cell lines in equilibrium in order to reduce a major potential source of biological variation, thus allowing the analysis to focus on the data integration methods in order to establish their performance. Conclusion: We conclude that much of the variation observed when integrating microarray and proteomics data may occur as a consequence both of the data analysis and of the high granularity to which studies have until recently been limited. The approach opens up the possibility for the first time of considering combined microarray and proteomics datasets at the level of individual exons and isoforms, important given the high proportion of alternative splicing observed in the human genome.
Exon level integration of proteomics and microarray data.
Cell line
View SamplesWe identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness (CSNB), congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions.
Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome.
Cell line
View SamplesStudies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply deep sequencing of RNA 3'' ends ("3-seq") to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed "skin aging") and the impact of broadband light (BBL) treatment. We find that skin aging was associated with the significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became "rejuvenated" after BBL treatment, i.e. more similar in expression level of youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long non-coding RNAs. Skin aging is not associated with systematic changes in 3'' end mRNA processing. Hence, BBL treatment can restore the gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveals a novel set of targets that may lead to new insights into the human skin aging process. Overall design: Examination of broadband light treated and untreated human skin transcriptomes of 5 women aged 50 years or more. They were compared to the skin transcriptomes of 5 young women aged 30 years or less.
Rejuvenation of gene expression pattern of aged human skin by broadband light treatment: a pilot study.
Sex, Specimen part, Treatment, Subject
View SamplesAs a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast the primary effector of the fibroproliferative response. A central unanswered question is whether these myofibroblasts have acquired a distinct pathological phenotype - or whether they are normal myofibroblasts with a pathological phenotype that depends upon residing in a sea of pro-fibrotic cytokines and an abnormal extracellular matrix.
Fibrotic myofibroblasts manifest genome-wide derangements of translational control.
No sample metadata fields
View SamplesDeregulation of translational control is an obligatory step in oncogenesis; however, this step has not been addressed by prior genomic and transcriptional profiling studies of cancer biology. Here we simulate the translational deregulation found in cancer by ectopically over expressing translation initiation factor eIF4E in primary human mammary epithelial cells; and examine its impact on cell biology and the pattern of ribosomal recruitment to mRNA genome wide. Over expression of eIF4E allows cells to bypass M0 premature growth arrest, but does not confer other malignant properties. However, in concert with hTERT, eIF4E imparts cells with growth and survival autonomy - and profoundly alters the pattern of polyribosome-associated mRNA encoding cell cycle and apoptosis regulators. The translational response to increased eIF4E is not only a unidirectional activation of oncogenic drivers, but also consists of complex intrinsic translational mechanisms that mitigate the acquisition of neoplastic properties.
Eukaryotic translation initiation factor 4E induced progression of primary human mammary epithelial cells along the cancer pathway is associated with targeted translational deregulation of oncogenic drivers and inhibitors.
No sample metadata fields
View SamplesThis is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies.
Noncoding RNA expression in myocardium from infants with tetralogy of Fallot.
Specimen part
View SamplesNext to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS senses signals from outside the cell and transmits them into the cytoplasm. It consists of a TonB-dependent outer membrane receptor, a cytoplasmic membrane-localized sigma factor regulator (or anti-sigma factor), and an extracytoplasmic function (ECF) sigma factor. Upon perception of the extracellular signal by the receptor the ECF sigma factor is activated and promotes the transcription of a specific set of gene(s). Although most P. aeruginosa ECF sigma factors are involved in the regulation of iron uptake, we have identified a novel ECF sigma factor (PA0675) involved in the regulation of virulence. By microarray analysis of cells overexpressing PA0675 from the pMUM3 plasmid we have identified the genes regulated by this sigma factor.
A Novel extracytoplasmic function (ECF) sigma factor regulates virulence in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThe data contained in this record are used to differentiate between the effects of IFN-a and IFN-b on 48h cultures of the ex vivo pbmcs of ATL patients, using Affymetrix microarrays (HuGene 1.0).
IFN-β induces greater antiproliferative and proapoptotic effects and increased p53 signaling compared with IFN-α in PBMCs of Adult T-cell Leukemia/Lymphoma patients.
Specimen part, Subject
View SamplesMyeloid progenitors derived from antibiotic-treated mice have cell-intrinsic functional defects. In this microarray dataset, the transcriptomes of bone marrow myeloid progenitors from antibiotic-treated and control mice are compared.
Microbiota-dependent signals are required to sustain TLR-mediated immune responses.
No sample metadata fields
View SamplesIdiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with a prevalence of one million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli, creating a reticular network that leads to death by asphyxiation. Lung fibroblasts from patients with IPF have phenotypic hallmarks, distinguishing them from their normal counterparts: pathologically activated Akt signaling axis, increased collagen and a-smooth muscle actin expression, distinct gene expression profile, and ability to form fibrotic lesions in model organisms. Despite the centrality of these fibroblasts in disease pathogenesis, their origin remains uncertain. Here, we report the identification of cells in the lungs of patients with IPF with the properties of mesenchymal progenitors. In contrast to progenitors isolated from nonfibrotic lungs, IPF mesenchymal progenitor cells produce daughter cells manifesting the full spectrum of IPF hallmarks, including the ability to form fibrotic lesions in zebrafish embryos and mouse lungs, and a transcriptional profile reflecting these properties. Morphological analysis of IPF lung tissue revealed that mesenchymal progenitor cells and cells with the characteristics of their progeny comprised the fibrotic reticulum. These data establish that the lungs of patients with IPF contain pathological mesenchymal progenitor cells that are cells of origin for fibrosis-mediating fibroblasts. These fibrogenic mesenchymal progenitors and their progeny represent an unexplored target for novel therapies to interdict fibrosis. Overall design: RNA-seq of lung fibroblasts from IPF or healthy control patients at day 0 or day 21 of culture.
Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis.
Specimen part, Disease, Disease stage, Subject
View Samples