A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis.
<h4>Background</h4>Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription f...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2010
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/57cf07fc99e548b88dcd763073a08da1 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:57cf07fc99e548b88dcd763073a08da1 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:57cf07fc99e548b88dcd763073a08da12021-11-18T07:02:12ZA transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis.1932-620310.1371/journal.pone.0014176https://doaj.org/article/57cf07fc99e548b88dcd763073a08da12010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21152067/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls.<h4>Methodology/principal findings</h4>We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value <3.31E-6; V$CREBP1_Q2, p-value <9.93E-6, V$YY1_02, p-value <1.65E-5).<h4>Conclusions/significance</h4>Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation.Carlos RiverosDrew MellorKaushal S GandhiFiona C McKayMathew B CoxRegina BerrettaS Yahya VaezpourMario Inostroza-PontaSimon A BroadleyRobert N HeardStephen VucicGraeme J StewartDavid W WilliamsRodney J ScottJeanette Lechner-ScottDavid R BoothPablo MoscatoANZgene Multiple Sclerosis Genetics ConsortiumPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14176 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Carlos Riveros Drew Mellor Kaushal S Gandhi Fiona C McKay Mathew B Cox Regina Berretta S Yahya Vaezpour Mario Inostroza-Ponta Simon A Broadley Robert N Heard Stephen Vucic Graeme J Stewart David W Williams Rodney J Scott Jeanette Lechner-Scott David R Booth Pablo Moscato ANZgene Multiple Sclerosis Genetics Consortium A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| description |
<h4>Background</h4>Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls.<h4>Methodology/principal findings</h4>We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value <3.31E-6; V$CREBP1_Q2, p-value <9.93E-6, V$YY1_02, p-value <1.65E-5).<h4>Conclusions/significance</h4>Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation. |
| format |
article |
| author |
Carlos Riveros Drew Mellor Kaushal S Gandhi Fiona C McKay Mathew B Cox Regina Berretta S Yahya Vaezpour Mario Inostroza-Ponta Simon A Broadley Robert N Heard Stephen Vucic Graeme J Stewart David W Williams Rodney J Scott Jeanette Lechner-Scott David R Booth Pablo Moscato ANZgene Multiple Sclerosis Genetics Consortium |
| author_facet |
Carlos Riveros Drew Mellor Kaushal S Gandhi Fiona C McKay Mathew B Cox Regina Berretta S Yahya Vaezpour Mario Inostroza-Ponta Simon A Broadley Robert N Heard Stephen Vucic Graeme J Stewart David W Williams Rodney J Scott Jeanette Lechner-Scott David R Booth Pablo Moscato ANZgene Multiple Sclerosis Genetics Consortium |
| author_sort |
Carlos Riveros |
| title |
A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| title_short |
A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| title_full |
A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| title_fullStr |
A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| title_full_unstemmed |
A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis. |
| title_sort |
transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mrna transcriptome in multiple sclerosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/57cf07fc99e548b88dcd763073a08da1 |
| work_keys_str_mv |
AT carlosriveros atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT drewmellor atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT kaushalsgandhi atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT fionacmckay atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT mathewbcox atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT reginaberretta atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT syahyavaezpour atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT marioinostrozaponta atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT simonabroadley atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT robertnheard atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT stephenvucic atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT graemejstewart atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT davidwwilliams atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT rodneyjscott atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT jeanettelechnerscott atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT davidrbooth atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT pablomoscato atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT anzgenemultiplesclerosisgeneticsconsortium atranscriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT carlosriveros transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT drewmellor transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT kaushalsgandhi transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT fionacmckay transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT mathewbcox transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT reginaberretta transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT syahyavaezpour transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT marioinostrozaponta transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT simonabroadley transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT robertnheard transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT stephenvucic transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT graemejstewart transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT davidwwilliams transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT rodneyjscott transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT jeanettelechnerscott transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT davidrbooth transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT pablomoscato transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis AT anzgenemultiplesclerosisgeneticsconsortium transcriptionfactormapasrevealedbyagenomewidegeneexpressionanalysisofwholebloodmrnatranscriptomeinmultiplesclerosis |
| _version_ |
1718424040564064256 |