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  • Computational Methods, Massively Parallel (Deep) Sequencing, Genomics  (1)
  • Interferon Regulatory Factor-7/deficiency/genetics/*metabolism  (1)
  • Lung/immunology/pathology/virology  (1)
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  • 1
    Publication Date: 2012-03-29
    Description: Next-generation sequencing (NGS) technologies-based transcriptomic profiling method often called RNA-seq has been widely used to study global gene expression, alternative exon usage, new exon discovery, novel transcriptional isoforms and genomic sequence variations. However, this technique also poses many biological and informatics challenges to extracting meaningful biological information. The RNA-seq data analysis is built on the foundation of high quality initial genome localization and alignment information for RNA-seq sequences. Toward this goal, we have developed RNASEQR to accurately and effectively map millions of RNA-seq sequences. We have systematically compared RNASEQR with four of the most widely used tools using a simulated data set created from the Consensus CDS project and two experimental RNA-seq data sets generated from a human glioblastoma patient. Our results showed that RNASEQR yields more accurate estimates for gene expression, complete gene structures and new transcript isoforms, as well as more accurate detection of single nucleotide variants (SNVs). RNASEQR analyzes raw data from RNA-seq experiments effectively and outputs results in a manner that is compatible with a wide variety of specialized downstream analyses on desktop computers.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2012-09-18
    Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation/*immunology ; Inflammation/genetics/*immunology/*pathology ; Interferon Regulatory Factor-7/deficiency/genetics/*metabolism ; Interferon Type I/immunology ; Lung/immunology/pathology/virology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Reproducibility of Results ; Vesiculovirus/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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