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  • Toleno, Donna M  (2)
  • Biodiversity Research  (2)
  • 1
    Online Resource
    Online Resource
    Development and evaluation of new mask protocols for gene expression profiling in humans and chimpanzees
    Springer Science and Business Media LLC ; 2009
    In:  BMC Bioinformatics Vol. 10, No. 1 ( 2009-12)
    Details
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2009-12)
    Abstract: Cross-species gene expression analyses using oligonucleotide microarrays designed to evaluate a single species can provide spurious results due to mismatches between the interrogated transcriptome and arrayed probes. Based on the most recent human and chimpanzee genome assemblies, we developed updated and accessible probe masking methods that allow human Affymetrix oligonucleotide microarrays to be used for robust genome-wide expression analyses in both species. In this process, only data from oligonucleotide probes predicted to have robust hybridization sensitivity and specificity for both transcriptomes are retained for analysis. Results To characterize the utility of this resource, we applied our mask protocols to existing expression data from brains, livers, hearts, testes, and kidneys derived from both species and determined the effects probe numbers have on expression scores of specific transcripts. In all five tissues, probe sets with decreasing numbers of probes showed non-linear trends towards increased variation in expression scores. The relationships between expression variation and probe number in brain data closely matched those observed in simulated expression data sets subjected to random probe masking. However, there is evidence that additional factors affect the observed relationships between gene expression scores and probe number in tissues such as liver and kidney. In parallel, we observed that decreasing the number of probes within probe sets lead to linear increases in both gained and lost inferences of differential cross-species expression in all five tissues, which will affect the interpretation of expression data subject to masking. Conclusion We introduce a readily implemented and updated resource for human and chimpanzee transcriptome analysis through a commonly used microarray platform. Based on empirical observations derived from the analysis of five distinct data sets, we provide novel guidelines for the interpretation of masked data that take the number of probes present in a given probe set into consideration. These guidelines are applicable to other customized applications that involve masking data from specific subsets of probes.
    Type of Medium: Online Resource
    ISSN: 1471-2105
    URL: Article
    DOI: 10.1186/1471-2105-10-77
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 2041484-5
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft
    Springer Science and Business Media LLC ; 2008
    In:  BMC Genomics Vol. 9, No. 1 ( 2008-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2008-12)
    Abstract: Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA) levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted ρ 0 counterparts grown in culture and as tumor xenografts in immune-deficient mice. Results Cultured A549 ρ 0 cells were respiration-deficient and showed enhanced levels of transcripts relevant to metal homeostasis, initiation of the epithelial-mesenchymal transition, and glucuronidation pathways. Several well-established HIF-regulated transcripts showed increased or decreased abundance relative to the parental cell line. Furthermore, growth in culture versus xenograft has a significantly greater influence on expression profiles, including transcripts involved in mitochondrial structure and both aerobic and anaerobic energy metabolism. However, both in vitro and in vivo , mtDNA levels explained the majority of the variance observed in the expression of transcripts in glucuronidation, tRNA synthetase, and immune surveillance related pathways. mtDNA levels in A549 xenografts also affected the expression of genes, such as AMACR and PHYH , involved in peroxisomal lipid metabolic pathways. Conclusion We have identified mtDNA-dependent gene expression profiles that are shared in cultured cells and in xenografts. These profiles indicate that mtDNA-depleted cells could provide informative model systems for the testing the efficacy of select classes of therapeutics, such as anti-angiogenesis agents. Furthermore, mtDNA-depleted cells grown culture and in xenografts provide a powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/1471-2164-9-521
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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