| ชื่อเรื่อง | : | Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages |
| นักวิจัย | : | Forster, Thorsten |
| คำค้น | : | meta-analysis , microarray , interferon , macrophages , statistics , bioinformatics |
| หน่วยงาน | : | Edinburgh Research Archive, United Kingdom |
| ผู้ร่วมงาน | : | Ghazal, Peter , Glasbey, Chris , Biotechnology and Biological Sciences Research Council (BBSRC) , Wellcome Trust , Medical Research Council (MRC) |
| ปีพิมพ์ | : | 2557 |
| อ้างอิง | : | http://hdl.handle.net/1842/9558 |
| ที่มา | : | - |
| ความเชี่ยวชาญ | : | - |
| ความสัมพันธ์ | : | The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response Blanc, M., Hsieh, W. Y., Robertson, K. A., Kropp, K. A., Forster, T., Shui, G., Lacaze, P., Watterson, S., Griffiths, S. J., Spann, N. J., Meljon, A., Talbot, S., Krishnan, K., Covey, D. F., Wenk, M. R., Craigon, M., Ruzsics, Z., Haas, J., Angulo, A., Griffiths, W. J., Glass, C. K., Wang, Y. & Ghazal, P.24-Jan-2013 In : Immunity.38, (1); 106-18 , Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis Blanc, M., Hsieh, W. Y., Robertson, K. A., Watterson, S., Shui, G., Lacaze, P., Khondoker, M., Dickinson, P., Sing, G., Rodríguez-Martín, S., Phelan, P., Forster, T., Strobl, B., Müller, M., Riemersma, R., Osborne, T., Wenk, M. R., Angulo, A. & Ghazal, P.2011 In : PLoS Biology.9, 3, p. e1000598 , Reversible inhibition of murine cytomegalovirus replication by gamma interferon (IFN-γ) in primary macrophages involves a primed type I IFN-signaling subnetwork for full establishment of an immediate-early antiviral state Kropp, K. A., Robertson, K. A., Sing, G., Rodriguez-Martin, S., Blanc, M., Lacaze, P., Hassim, M. F. B. N., Khondoker, M. R., Busche, A., Dickinson, P., Forster, T., Strobl, B., Mueller, M., Jonjic, S., Angulo, A. & Ghazal, P.2011 In : Journal of Virology.85, 19, p. 10286-99, 14 p. , Combined genome-wide expression profiling and targeted RNA interference in primary mouse macrophages reveals perturbation of transcriptional networks associated with interferon signalling Lacaze, P., Raza, S., Sing, G., Page, D., Forster, T., Storm, P., Craigon, M., Awad, T., Ghazal, P. & Freeman, T. C.Aug-2009 In : BMC Genomics.10, 372 , Estimation of expression levels in spotted microarrays with saturated pixels Glasbey, C. A., Forster, T. & Ghazal, P.2007 In : Statistical applications in genetics and molecular biology.6, p. Article34 , Modelling of macrophage gene expression in the interferon pathway Yu, L., Marshall, S., Forster, T. & Ghazal, P.2006 2006 IEEE International Workshop on Genomic Signal Processing and Statistics. NEW YORK: IEEE, p. 45-462 p. , GPX-Macrophage Expression Atlas: a database for expression profiles of macrophages challenged with a variety of pro-inflammatory, anti-inflammatory, benign and pathogen insults Grimes, G. R., Moodie, S., Beattie, J. S., Craigon, M., Dickinson, P., Forster, T., Livingston, A. D., Mewissen, M., Robertson, K. A., Ross, A. J., Sing, G. & Ghazal, P.12-Dec-2005 In : BMC Genomics.6, 178, p. 1-8, 8 p. , Microarrays - Standard operating procedures. Ghazal, P. & Forster, T.2005Encyclopedia of Medical Genomics and Proteomics. Fuchs, J. (ed.). MARCEL DEKKER, p. 824-8306 p. , Exploiting Parallel R in the Cloud with SPRINT Piotrowski, M., McGilvary, G. A., Sloan, T. M., Mewissen, M., Lloyd, A. D., Forster, T., Mitchell, L., Ghazal, P. & Hill, J. Jan-2013 In : Methods of Information in Medicine.52, 1, p. 80-90, 11 p. , SPRINT v1.0.4 Software Release Troup, E., Mitchell, L., Sloan, T., Robertson, K., Forster, T. & Ghazal, P.Jan-2013 , Parallel classification and feature selection in microarray data using SPRINT Mitchell, L., Sloan, T. M., Mewissen, M., Ghazal, P., Forster, T., Piotrowski, M. & Trew, A.2012 In : Concurrency and Computation: Practice and Experience.p. n/a-n/a , Optimization of a parallel permutation testing function for the SPRINT R package Petrou, S., Sloan, T., Mewissen, M., Forster, T., Piotrowski, M., Dobrzelecki, B., Ghazal, P., Trew, A. & Hill, J. 10-Dec-2011 In : Concurrency and Computation: Practice and Experience.23, 17, p. 2258-2268, 11 p. , Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks Lowrie, A. G., Dickinson, P., Wheelhouse, N., Stewart, G. D., Ross, A. J., Forster, T. & Ross, J. A.Sep-2011 In : International journal of oncology.39, 3, p. 709-718, 10 p. , Optimisation and parallelisation of the partitioning around medoids function in R Piotrowski, M., Forster, T., Dobrezelecki, B., Sloan, T., Mitchell, L., Ghazal, P., Mewsissen, M., Petrou, S., Trew, A. & Hill, J. 1-Jul-2011p. 707-7137 p. , A parallel random forest classifier for R Mitchell, L., Sloan, T., Mewissen, M., Ghazal, P., Forster, T., Piotrowski, M. & Trew, A. S.1-Jan- 2011p. 1-67 p. , Optimization of a parallel permutation testing function for the SPRINT R package Petrou, S., Sloan, T. M., Mewissen, M., Forster, T., Piotrowski, M., Dobrzelecki, B., Ghazal, P., Trew, A. & Hill, J. 2011 In : Concurrency and Computation: Practice and Experience.23, 17, p. 2258-2268, 11 p. , Temporal profiling of the coding and noncoding murine cytomegalovirus transcriptomes Lacaze, P., Forster, T., Ross, A., Kerr, L. E., Salvo-Chirnside, E., Lisnic, V. J., López-Campos, G. H., García-Ramírez, J. J., Messerle, M., Trgovcich, J., Angulo, A. & Ghazal, P.2011 In : Journal of Virology.85, 12, p. 6065-76, 12 p. , Assessment of transcriptomal analysis of varicella-zoster-virus gene expression in patients with and without post-herpetic neuralgia Ashrafi, G. H., Grinfeld, E., Montague, P., Forster, T., Ross, A., Ghazal, P., Scott, F., Breuer, J., Goodwin, R. & Kennedy, P. G. E. Oct-2010 In : Virus Genes.41, 2, p. 192-201, 10 p. , Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs Santhakumar, D., Forster, T., Laqtom, N. N., Fragkoudis, R., Dickinson, P., Abreu-Goodger, C., Manakov, S. A., Choudhury, N. R., Griffiths, S. J., Vermeulen, A., Enright, A. J., Dutia, B., Kohl, A., Ghazal, P. & Buck, A. H.Aug-2010 In : Proceedings of the National Academy of Sciences of the United States of America - PNAS.107, 31, p. 13830-13835, 6 p. , SPRINT: a Simple Parallel INTerface to High Performance Computing and a Parallel R Function Library. Mewissen, M., Forster, T., Sloan, T., Petrou, S., Piotrowski, M., Dobrzelecki, B., Ghazal, P., Trew, A. & Hill, J. Jul-2010p. 1051 p. , Quantitative analysis of low-abundance peptides in HeLa cell cytoplasm by targeted liquid chromatography/mass spectrometry and stable isotope dilution: emphasising the distinction between peptide detection and peptide identification Le Bihan, T., Grima, R., Martin, S., Forster, T. & Le Bihan, Y. Apr-2010 In : Rapid communications in mass spectrometry.24, 7, p. 1093-1104, 12 p. , Applying statistical inference in genomics with evidence-based pathways: Towards elucidating new functional correlations of biomarkers. Ghazal, P., Forster, T. & Ivens, A.22-Feb-2010 In : European Pharmaceutical Review.1, p. 12-15 , Optimization of a parallel permutation testing function for the SPRINT R package Petrou, S., Sloan, T., Mewissen, M., Forster, T., Piotrowski, M. & Dobrzelecki, B. 1-Jan-2010p. 516-5216 p. , Statistical methods for analysis of high-throughput RNA interference screens Birmingham, A., Selfors, L. M., Forster, T., Wrobel, D., Kennedy, C. J., Shanks, E., Santoyo- Lopez, J., Dunican, D. J., Long, A., Kelleher, D., Smith, Q., Beijersbergen, R. L., Ghazal, P. & Shamu, C. E. Aug-2009 In : Nature Methods.6, 8, p. 569-575, 7 p. , Genome-wide reduction in transcriptomal profiles of varicella-zoster virus vaccine strains compared with Parental Oka strain using long oligonucleotide microarrays Grinfeld, E., Ross, A., Forster, T., Ghazal, P. & Kennedy, P. Feb-2009 In : Virus Genes.38, 1, p. 19-29, 11 p. , Transcriptomal analysis of Varicella-Zoster-Virus gene expression in patients with and without Post-Herpetic Neuralgia Ashrafi, H., Grinfeld, E., Forster, T., Ross, A., Ghazal, P., Breuer, J., Goodwin, R. & Kennedy, P. G. E. 2009 In : Journal of Neurovirology.15, p. 77, 1 p. , High-resolution gene expression profiling for simultaneous kinetic parameter analysis of RNA synthesis and decay Dolken, L., Ruzsics, Z., Radle, B., Friedel, C. C., Zimmer, R., Mages, J., Hoffmann, R., Dickinson, P., Forster, T., Ghazal, P. & Koszinowski, U. H. Sep-2008 In : RNA.14, 9, p. 1959-1972, 14 p. , Evaluation of a protein microarray method for immuno-typing erythrocytes in whole blood O'Looney, N., Burgess, S. T. G., Kwan, M. C., Ross, A. J., Robb, J., Forster, T., Beattie, J. S., Ghazal, P., Petrik, J. & Campbell, C. J. 2008 In : Journal of Immunoassay and Immunochemistry.29, 2, p. 197-209, 13 p. , Molecular profiling of the human testis reveals stringent pathway-specific regulation of RNA expression following gonadotropin suppression and progestogen treatment Bayne, R. A. L., Forster, T., Burgess, S. T. G., Craigon, M., Walton, M. J., Baird, D. T., Ghazal, P. & Anderson, R. A.2008 In : Journal of Andrology.29, 4, p. 389-403, 15 p. , SPRINT: a new parallel framework for R Hill, J., Hambley, M., Forster, T., Mewissen, M., Sloan, T., Scharinger, F., Trew, A. & Ghazal, P.2008 In : BMC Bioinformatics.9, p. 558 , Investigation of host RNA responses to infection in neonates: a new avenue for diagnosis? Smith, C. L., Dickinson, P., Forster, T., Lacaze, P., Stenson, B. J. & Ghazal, P.Oct-2007 In : Acta paediatrica.96, p. 88, 1 p. , Quantitative assessment of human whole blood RNA as a potential biomarker for infectious disease Smith, C. L., Dickinson, P., Forster, T., Khondoker, M., Craigon, M., Ross, A., Storm, P., Burgess, S., Lacaze, P., Stenson, B. J. & Ghazal, P.2007 In : Analyst.132, 12, p. 1200-9, 10 p. , Innate immune response gene expression profiles of N9 microglia are pathogen-type specific McKimmie, C. S., Roy, D., Forster, T. & Fazakerley, J. K. Jun-2006 In : Journal of neuroimmunology.175, 1-2, p. 128-141, 14 p. , Gene expression profiling of mid to late secretory phase endometrial biopsies from women with menstrual complaint Critchley, H. O. D., Robertson, K. A., Forster, T., Henderson, T. A., Williams, A. R. W. & Ghazal, P.2006 In : American journal of obstetrics and gynecology.195, 2, p. 406.e1-16 , Locus-specific gene expression pattern suggests a unique propagation strategy for a giant algal virus Allen, M. J., Forster, T., Schroeder, D. C., Hall, M., Roy, D., Ghazal, P. & Wilson, W. H. 2006 In : Journal of Virology.80, 15, p. 7699-705, 7 p. , Microarray and bioarray technology. Ghazal, P. & Forster, T.2005Bioinformatics Baiscs: Applications in biological science and medicine.: Second Edicition. Buehler, L. K. & Rashidi, H. H. (eds.). CRC press, p. 190-21626 p. , Transcriptomal analysis of varicella-zoster virus infection using long oligonucleotide-based microarrays Kennedy, P. G. E., Grinfeld, E., Craigon, M., Vierlinger, K., Roy, D., Forster, T. & Ghazal, P.2005 In : Journal of General Virology.86, Pt 10, p. 2673-84, 12 p. , Triple-target microarray experiments: a novel experimental strategy Forster, T., Costa, Y., Roy, D., Cooke, H. J. & Maratou, K. 10-Feb-2004 In : BMC Genomics.5, p. -, 16 p., 13 , Expression profiling of the developing testis in wild-type and Dazl knockout mice Maratou, K., Forster, T., Costa, Y., Taggart, M., Speed, R. M., Ireland, J., Teague, P., Roy, D. & Cooke, H. J. Jan-2004 In : Molecular Reproduction and Development.67, 1, p. 26-54, 29 p. , Steroid signalling in human ovarian surface epithelial cells: the response to interleukin- 1alpha determined by microarray analysis Rae, M. T., Niven, D., Ross, A., Forster, T., Lathe, R., Critchley, H. O. D., Ghazal, P. & Hillier, S. G. 2004 In : Journal of Endocrinology.183, 1, p. 19-28, 10 p. , Gene expression responses induced in kidney by aldosterone excess and salt Marshall, E., Dickinson, P., Forster, T., Roy, D., Kenyon, C. J. & Brown, R. W. Nov-2003 In : Journal of the American Society of Nephrology.14, p. 140A-140A, 1 p. , Experiments using microarray technology: limitations and standard operating procedures Forster, T., Roy, D. & Ghazal, P.2003 In : Journal of Endocrinology.178, 2, p. 195-204, 10 p. , Meeting review: Bioinformatics of biochips: Accelerating discovery in functional genomics Roy, D., Forster, T., McGeever, S., Robertson, K. N. & Ghazal, P.Aug-2002 In : Comparative and functional genomics.3, 4, p. 380-386, 7 p. , Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index Hawkins, R. A., Tesdale, A. L., Prescott, R. J., Forster, T., McIntyre, M. A., Baker, P., Jack, W. J. L., Chetty, U., Dixon, J. M., Killen, M. E., Hulme, M. J. & Miller, W. R. 1-Jul-2002 In : British Journal of Cancer.87, 1, p. 814, 7 p. , Effect of a national community intervention programme on healing rates of chronic leg ulcer: Randomised controlled trial Brown, A., Burns, E., Chalmers, L., Corcoran, F., Dale, J., Douglas, S., Finnie, A., Forster, T., Fowkes, G., Gibson, B., Gillies, T., Hill, E., Lee, R., MacGuire, C., Morley, S., O'Hare, J., Prescott, R., Ruckley, V., Young, C. & Scottish Leg Ulser Trial Participa 2002 In : Phlebology.17, 2, p. 47-53, 7 p. |
| ขอบเขตของเนื้อหา | : | - |
| บทคัดย่อ/คำอธิบาย | : | Interferon gamma (IFN-γ) regulation of macrophages plays an essential role in innate immunity and pathogenicity of viral infections by directing large and small genome-wide changes in the transcriptional program of macrophages. Smaller changes at the transcriptional level are difficult to detect but can have profound biological effects, motivating the hypothesis of this thesis that responses of macrophages to immune activation by IFN-γ include small quantitative changes that are masked by noise but represent meaningful transcriptional systems in pathways against infection. To test this hypothesis, statistical meta-analysis of microarray studies is investigated as a tool to obtain the necessary increase in analysis sensitivity. Three meta-analysis models (Effect size model, Rank Product model, Fisher’s sum of logs) and three further modified versions were applied to a heterogeneous set of four microarray studies on the effect of IFN-γ on murine macrophages. Performance assessments include recovery of known biology and are followed by development of novel biological hypotheses through secondary analysis of meta-analysis outcomes in context of independent biological data sources. A separate network analysis of a microarray time course study investigate s if gene sets with coordinated time-dependent relationships overlap can also identify subtle IFN-γ related transcriptional changes in macrophages that match those identified through meta-analysis. It was found that all meta-analysis models can identify biologically meaningful transcription at enhanced sensitivity levels, with slightly improved performance advantages for a non-parametric model (Rank Product meta-analysis). Meta-analysis yielded consistently regulated genes, hidden in individual microarray studies, related to sterol biosynthesis (Stard3, Pgrmc1, Galnt6, Rab11a, Golga4, Lrp10), implicated in cross-talk between type II and type I interferon or IL-10 signalling (Tbk1, Ikbke, Clic4, Ptpre, Batf), and circadian rhythm (Csnk1e). Further network analysis confirms that meta-analysis findings are highly concentrated in a distinct immune response cluster of co-expressed genes, and also identifies global expression modularisation in IFN-γ treated macrophages, pointing to Trafd1 as a central anti-correlated node topologically linked to interactions with down-regulated sterol biosynthesis pathway members. Outcomes from this thesis suggest that small transcriptional changes in IFN-γ activated macrophages can be detected by enhancing sensitivity through combination of multiple microarray studies. Together with use of bioinformatical resources, independent data sets and network analysis, further validation assigns a potential role for low or variable transcription genes in linking type II interferon signalling to type I and TLR signalling, as well as the sterol metabolic network. |
| บรรณานุกรม | : |
Forster, Thorsten . (2557). Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages.
กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom . Forster, Thorsten . 2557. "Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages".
กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom . Forster, Thorsten . "Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages."
กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom , 2557. Print. Forster, Thorsten . Statistical modelling of masked gene regulatory pathway changes across microarray studies of interferon gamma activated macrophages. กรุงเทพมหานคร : Edinburgh Research Archive, United Kingdom ; 2557.
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