6 results on '"Workman, Christopher T."'
Search Results
2. Bidirectional histone-gene promoters in Aspergillus: characterization and application for multi-gene expression
- Author
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Rendsvig, Jakob K. H., Workman, Christopher T., and Hoof, Jakob B.
- Published
- 2019
- Full Text
- View/download PDF
3. Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.
- Author
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Ewald, David A., Malajian, Dana, Krueger, James G., Workman, Christopher T., Tianjiao Wang, Suyan Tian, Litman, Thomas, Guttman-Yassky, Emma, and Suárez-Fariñas, Mayte
- Subjects
META-analysis ,ATOPIC dermatitis ,GENETIC transcription ,ATHEROSCLEROSIS ,LIPID metabolism - Abstract
Background: Atopic dermatitis (AD) is a common inflammatory skin disease with limited treatment options. Several microarray experiments have been conducted on lesional/LS and non-lesional/NL AD skin to develop a genomic disease phenotype. Although these experiments have shed light on disease pathology, inter-study comparisons reveal large differences in resulting sets of differentially expressed genes (DEGs), limiting the utility of direct comparisons across studies. Methods: We carried out a meta-analysis combining 4 published AD datasets to define a robust disease profile, termed meta-analysis derived AD (MADAD) transcriptome. Results: This transcriptome enriches key AD pathways more than the individual studies, and associates AD with novel pathways, such as atherosclerosis signaling (IL-37, selectin E/SELE). We identified wide lipid abnormalities and, for the first time in vivo, correlated Th2 immune activation with downregulation of key epidermal lipids (FA2H, FAR2, ELOVL3), emphasizing the role of cytokines on the barrier disruption in AD. Key AD "classifier genes" discriminate lesional from nonlesional skin, and may evaluate therapeutic responses. Conclusions: Our meta-analysis provides novel and powerful insights into AD disease pathology, and reinforces the concept of AD as a systemic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
4. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.
- Author
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Li Jiang, Edwards, Stefan M., Thomsen, Bo, Workman, Christopher T., Guldbrandtsen, Bernt, and Sørensen, Peter
- Abstract
Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. Results: We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. Conclusion: We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
5. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design.
- Author
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Fazio, Alessandro, Jewett, Michael C., Daran-Lapujade, Pascale, Mustacchi, Roberta, Usaite, Renata, Pronk, Jack T., Workman, Christopher T., and Nielsen, Jens
- Subjects
TRANSCRIPTION factors ,GROWTH factors ,GENETIC regulation ,SACCHAROMYCES cerevisiae ,FUNGAL gene expression ,MESSENGER RNA ,FUNGAL genetics - Abstract
Background: Characterization of cellular growth is central to understanding living systems. Here, we applied a three-factor design to study the relationship between specific growth rate and genome-wide gene expression in 36 steady-state chemostat cultures of Saccharomyces cerevisiae. The three factors we considered were specific growth rate, nutrient limitation, and oxygen availability. Results: We identified 268 growth rate dependent genes, independent of nutrient limitation and oxygen availability. The transcriptional response was used to identify key areas in metabolism around which mRNA expression changes are significantly associated. Among key metabolic pathways, this analysis revealed de novo synthesis of pyrimidine ribonucleotides and ATP producing and consuming reactions at fast cellular growth. By scoring the significance of overlap between growth rate dependent genes and known transcription factor target sets, transcription factors that coordinate balanced growth were also identified. Our analysis shows that Fhl1, Rap1, and Sfp1, regulating protein biosynthesis, have significantly enriched target sets for genes up-regulated with increasing growth rate. Cell cycle regulators, such as Ace2 and Swi6, and stress response regulators, such as Yap1, were also shown to have significantly enriched target sets. Conclusion: Our work, which is the first genome-wide gene expression study to investigate specific growth rate and consider the impact of oxygen availability, provides a more conservative estimate of growth rate dependent genes than previously reported. We also provide a global view of how a small set of transcription factors, 13 in total, contribute to control of cellular growth rate. We anticipate that multi-factorial designs will play an increasing role in elucidating cellular regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
6. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.
- Author
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Jiang L, Edwards SM, Thomsen B, Workman CT, Guldbrandtsen B, and Sørensen P
- Subjects
- Algorithms, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Likelihood Functions, Models, Statistical, Phenotype, Protein Interaction Maps, Reproducibility of Results, Data Mining methods, Databases, Genetic, Disease genetics, Genomics methods, Proteins genetics, Proteins metabolism, PubMed
- Abstract
Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization., Results: We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance., Conclusion: We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data from genome-wide association studies, and will help in the understanding of how the associated genetic variants influence disease or quantitative phenotypes.
- Published
- 2014
- Full Text
- View/download PDF
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