4 results on '"Andrews, Justen"'
Search Results
2. DNA copy number evolution in Drosophila cell lines.
- Author
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Lee H, McManus CJ, Cho DY, Eaton M, Renda F, Somma MP, Cherbas L, May G, Powell S, Zhang D, Zhan L, Resch A, Andrews J, Celniker SE, Cherbas P, Przytycka TM, Gatti M, Oliver B, Graveley B, and MacAlpine D
- Subjects
- Animals, Cell Survival, DNA analysis, Drosophila Proteins genetics, Female, Genetic Fitness, Genetic Variation, Male, MicroRNAs genetics, Receptor Protein-Tyrosine Kinases genetics, Selection, Genetic, Sequence Analysis, DNA, Sex Chromosomes genetics, Tissue Culture Techniques, Cell Line, Drosophila melanogaster cytology, Drosophila melanogaster genetics, Evolution, Molecular, Gene Dosage
- Abstract
Background: Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles., Results: Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167)., Conclusion: Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis.
- Published
- 2014
- Full Text
- View/download PDF
3. Mediation of Drosophila autosomal dosage effects and compensation by network interactions.
- Author
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Malone JH, Cho DY, Mattiuzzo NR, Artieri CG, Jiang L, Dale RK, Smith HE, McDaniel J, Munro S, Salit M, Andrews J, Przytycka TM, and Oliver B
- Subjects
- Animals, Animals, Genetically Modified genetics, Chromosomes, Insect genetics, Female, Gene Dosage, Genetic Heterogeneity, Male, Oligonucleotide Array Sequence Analysis methods, Transcriptome, X Chromosome genetics, Dosage Compensation, Genetic, Drosophila genetics, Gene Regulatory Networks, Genes, Insect
- Abstract
Background: Gene dosage change is a mild perturbation that is a valuable tool for pathway reconstruction in Drosophila. While it is often assumed that reducing gene dose by half leads to two-fold less expression, there is partial autosomal dosage compensation in Drosophila, which may be mediated by feedback or buffering in expression networks., Results: We profiled expression in engineered flies where gene dose was reduced from two to one. While expression of most one-dose genes was reduced, the gene-specific dose responses were heterogeneous. Expression of two-dose genes that are first-degree neighbors of one-dose genes in novel network models also changed, and the directionality of change depended on the response of one-dose genes., Conclusions: Our data indicate that expression perturbation propagates in network space. Autosomal compensation, or the lack thereof, is a gene-specific response, largely mediated by interactions with the rest of the transcriptome.
- Published
- 2012
- Full Text
- View/download PDF
4. Gene networks in Drosophila melanogaster: integrating experimental data to predict gene function.
- Author
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Costello JC, Dalkilic MM, Beason SM, Gehlhausen JR, Patwardhan R, Middha S, Eads BD, and Andrews JR
- Subjects
- Algorithms, Animals, Cluster Analysis, Computational Biology, Databases, Genetic, Databases, Protein, Genomics methods, Oligonucleotide Array Sequence Analysis, Systems Integration, Drosophila melanogaster genetics, Gene Expression Profiling statistics & numerical data, Gene Regulatory Networks, Protein Interaction Mapping statistics & numerical data
- Abstract
Background: Discovering the functions of all genes is a central goal of contemporary biomedical research. Despite considerable effort, we are still far from achieving this goal in any metazoan organism. Collectively, the growing body of high-throughput functional genomics data provides evidence of gene function, but remains difficult to interpret., Results: We constructed the first network of functional relationships for Drosophila melanogaster by integrating most of the available, comprehensive sets of genetic interaction, protein-protein interaction, and microarray expression data. The complete integrated network covers 85% of the currently known genes, which we refined to a high confidence network that includes 20,000 functional relationships among 5,021 genes. An analysis of the network revealed a remarkable concordance with prior knowledge. Using the network, we were able to infer a set of high-confidence Gene Ontology biological process annotations on 483 of the roughly 5,000 previously unannotated genes. We also show that this approach is a means of inferring annotations on a class of genes that cannot be annotated based solely on sequence similarity. Lastly, we demonstrate the utility of the network through reanalyzing gene expression data to both discover clusters of coregulated genes and compile a list of candidate genes related to specific biological processes., Conclusions: Here we present the the first genome-wide functional gene network in D. melanogaster. The network enables the exploration, mining, and reanalysis of experimental data, as well as the interpretation of new data. The inferred annotations provide testable hypotheses of previously uncharacterized genes.
- Published
- 2009
- Full Text
- View/download PDF
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