The innate immune response is primarily mediated by the Toll-like receptors functioning through the Myd88-dependent and TRIF-dependent pathways. Despite being widely studied, it is not yet completely understood and systems-level analyses have been lacking. In this study, we identified a high-probability network of genes activated during the innate immune response using a novel approach to analyze time course gene expression profiles of activated immune cells in combination with a large gene regulatory and protein-protein interaction network. We classified the immune response into three consecutive time-dependent stages and identified the most probable paths between genes showing a significant change in expression at each stage. The resultant network contained several novel and known regulators of the innate immune response, many of which did not show any observable change in expression at the sampled time points. The response network shows the dominance of genes from specific functional classes during different stages of the immune response. It also suggests a role for the protein phosphatase 2a catalytic subunit a in the regulation of the immunoproteasome during the late phase of the response. In order to clarify the differences between the Myd88-dependent and TRIF-dependent pathways in the innate immune response, time course gene expression profiles from Myd88-knockout and TRIF-knockout dendritic cells were analyzed. Their response networks suggest the dominance of the MyD88 dependent pathway in the innate immune response, and an association of the circadian regulators and immunoproteasomal degradation with the TRIF-dependent pathway. The response network presented here provides the most probable associations between genes expressed in the early and the late phases of the immune response, while taking into account the intermediate regulators. We propose that the method described here can also be used in the identification of time-dependent gene subnetworks in other biological systems.
Discovery of Intermediary Genes between Pathways Using Sparse Regression.
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View SamplesCell lines derived from tumor tissues have been used as a valuable system tostudy gene regulation and cancer development. Comprehensive characterization ofthe genetic background of cell lines could provide clues on novel genes responsiblefor carcinogenesis and help in choosing cell lines for particular studies. Here, we havecarried out whole exome and RNA sequencing of commonly used glioblastoma (GBM)cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotidevariations (SNVs), indels, differential gene expression, gene fusions and RNA editingevents. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) werepotentially cancer-specific. The cell lines showed frequent SNVs and indels in someof the genes that are known to be altered in GBM- EGFR, TP53, PTEN, SPTA1 andNF1. Chromatin modifying genes- ATRX, MLL3, MLL4, SETD2 and SRCAP also showedalterations. While no cell line carried IDH1 mutations, five cell lines showed hTERTpromoter activating mutations with a concomitant increase in hTERT transcript levels.Five significant gene fusions were found of which NUP93-CYB5B was validated. Anaverage of 18,949 RNA editing events was also obtained. Thus we have generated acomprehensive catalogue of genetic alterations for six GBM cell lines.
Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing.
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View SamplesBackground
Global transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3.
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View SamplesAcute lung rejection is a risk factor for chronic rejection, jeopardizing the long-term survival of lung transplant recipients. At present, acute rejection is diagnosed by transbronchial lung biopsies, which are invasive, expensive, and subject to significant sampling error. In this study, we sought to identify groups of genes whose collective expression in BAL cells best classifies acute rejection versus no-rejection. BAL samples were analyzed from 32 unique subjects whose concurrent histology showed acute rejection (n=14) or no rejection (n=18). Global BAL cell gene expression was measured using Affymetrix U133A microarrays. The nearest shrunken centroid method with 10-fold cross validation was used to define the classification model. 250 runs of the algorithm were performed to determine the range of misclassification error and the most influential genes in determining classifiers. The estimated overall misclassification rate was below 20%. Seven transcripts were present in every classifier and 52 transcripts were present in at least 70% of classifiers; these transcripts were notable for involvement with T-cell function, cytotoxic CD8 activity, and granulocyte degranulation. The proportions of both lymphocytes and neutrophils in BAL samples increased with increasing probability of acute rejection; this trend was more pronounced with neutrophils. We conclude that there is a prominent acute rejection-associated signature in BAL cells characterized by increased T-cell, CD8+ cytotoxic cell, and neutrophil gene expression; this is consistent with established mechanistic concepts of the acute rejection response.
Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier.
No sample metadata fields
View SamplesComparative genomic analysis of nutrient response to NO3-, NH4+ or NH4+: NO3- in barley
Global transcriptional and physiological responses of Saccharomyces cerevisiae to ammonium, L-alanine, or L-glutamine limitation.
Age, Specimen part, Subject, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes beween AA cancer and patient matched normal tissues.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in AA and EA patients.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesProstate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling analysis using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes in EA PCa vs. EA normal.
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Specimen part
View SamplesThe analysis of capped RNAs by massively parallel sequencing has identified a large number of previously unknown transcripts, some of which are small RNAs and others are 5 truncated forms of RefSeq genes. The latter may be generated by endonuclease cleavage or by stalling of Xrn1 at defined sites. With the exception of promoter-proximal transcripts the caps on all of these are added post-transcriptionally by a cytoplasmic capping enzyme complex that includes capping enzyme and a kinase that converts 5-monophosphate ends to a diphosphate capping substrate. We previously described a modified form of capping enzyme with dominant negative activity against cytoplasmic capping (DN-cCE). A tet-inducible form of this was used to identify substrates for cytoplasmic capping by treating cytoplasmic RNA from control and induced cells with and without Xrn1. Surviving RNA was analyzed on Affymetrix Human Exon 1.0 arrays and scored for changes in probe intensity as a function of its position on each RefSeq gene to derive a factor (alpha) that could be compared between sets. Notably, transcriptome-wide changes were not evident unless RNA was treated with Xrn1. This analysis identified 2,666 uncapped mRNAs in uninduced cells, 672 mRNAs that appeared in the uncapped pool in cells expressing DN-cCE, and 835 mRNAs that were in both populations. Changes in cap status of 10 re-capping targets and 5 controls were assessed by 3 independent measures; susceptibility to Xrn1, recovery with a biotin-tagged DNA primer after ligating a complementary RNA oligonucleotide to uncapped 5 ends, and binding or exclusion from a high affinity cap-binding matrix comprised of immobilized eIF4E and the corresponding binding domain of eIF4G.
Identification of cytoplasmic capping targets reveals a role for cap homeostasis in translation and mRNA stability.
Cell line
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