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GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets
BACKGROUND: Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type (‘outlier genes’), a hallmark of p...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041823/ https://www.ncbi.nlm.nih.gov/pubmed/21365010 http://dx.doi.org/10.1371/journal.pone.0017259 |
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author | Mpindi, John Patrick Sara, Henri Haapa-Paananen, Saija Kilpinen, Sami Pisto, Tommi Bucher, Elmar Ojala, Kalle Iljin, Kristiina Vainio, Paula Björkman, Mari Gupta, Santosh Kohonen, Pekka Nees, Matthias Kallioniemi, Olli |
author_facet | Mpindi, John Patrick Sara, Henri Haapa-Paananen, Saija Kilpinen, Sami Pisto, Tommi Bucher, Elmar Ojala, Kalle Iljin, Kristiina Vainio, Paula Björkman, Mari Gupta, Santosh Kohonen, Pekka Nees, Matthias Kallioniemi, Olli |
author_sort | Mpindi, John Patrick |
collection | PubMed |
description | BACKGROUND: Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type (‘outlier genes’), a hallmark of potential oncogenes. METHODOLOGY: A new statistical method (the gene tissue index, GTI) was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29) of these genes, and 17 of these 19 genes (90%) showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target. CONCLUSIONS/SIGNIFICANCE: Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is implemented in an R package (Text S1). |
format | Text |
id | pubmed-3041823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30418232011-03-01 GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets Mpindi, John Patrick Sara, Henri Haapa-Paananen, Saija Kilpinen, Sami Pisto, Tommi Bucher, Elmar Ojala, Kalle Iljin, Kristiina Vainio, Paula Björkman, Mari Gupta, Santosh Kohonen, Pekka Nees, Matthias Kallioniemi, Olli PLoS One Research Article BACKGROUND: Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type (‘outlier genes’), a hallmark of potential oncogenes. METHODOLOGY: A new statistical method (the gene tissue index, GTI) was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29) of these genes, and 17 of these 19 genes (90%) showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target. CONCLUSIONS/SIGNIFICANCE: Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is implemented in an R package (Text S1). Public Library of Science 2011-02-18 /pmc/articles/PMC3041823/ /pubmed/21365010 http://dx.doi.org/10.1371/journal.pone.0017259 Text en Mpindi et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mpindi, John Patrick Sara, Henri Haapa-Paananen, Saija Kilpinen, Sami Pisto, Tommi Bucher, Elmar Ojala, Kalle Iljin, Kristiina Vainio, Paula Björkman, Mari Gupta, Santosh Kohonen, Pekka Nees, Matthias Kallioniemi, Olli GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title | GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title_full | GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title_fullStr | GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title_full_unstemmed | GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title_short | GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets |
title_sort | gti: a novel algorithm for identifying outlier gene expression profiles from integrated microarray datasets |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041823/ https://www.ncbi.nlm.nih.gov/pubmed/21365010 http://dx.doi.org/10.1371/journal.pone.0017259 |
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