Contributions
Abstract: EP1422
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Cellular mechanisms controlling cell death and proliferation play a crucial role in the pathogenesis of multiple sclerosis (MS). DJ-1/PARK7 is a multifunctional cytoprotective protein that has been reported to be upregulated in multiple sclerosis, both in brain samples and CSF versus controls. Furthermore, in a previous study, we derived a gene signature from the PARK7 interactome, implicated in histone deacetylation and chromatin remodeling processes in maliganant pleural mesothelioma (1) ; Epigenetic mechanisms have been shown to contribute to propagating autoreactivity in MS (2).
Goals: The objective of our study is to determine whether PARK7 and its network are differentially expressed in MS.
Methods: The GEOprofiles repository (3) was interrogated using the keywords “peripheral, blood, mononuclear, cells, park7”. Profile data (GSE21942 ) for a previously constructed PARK7 network (1) were downloaded. Differentially expressed genes (DEGs) were identified using independent samples t-test, as per the original GEOprofiles platform built-in analyses. Probes referring to the same gene were tested via the BLAST tool for sequence coverage (Human Genomic plus Transcript Database). Both mean (between-probe) and individual probe (post-BLAST verification) data were tested in a multivariate model employing stepwise linear discriminant function analysis (DFA). Gene ontology annotations were performed through the GENEmania tool.
Results: Gene expression profile GSE21942 data were downloaded form GEOprofiles in 17/4/16. Out of 13 genes, PARK7, SOD1, SUMO1, PIAS2, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7 and HSPA4 were differentially expressed in MS patients vs controls (p-value < 0.05). Stepwise linear discriminant function analysis (DFA) constructed a predictive model (Wilk"s λ=0.117, χ2=53.683, p=6.1314e-11) with 4 coefficients (BBS1, SUMO1, RBBP4, HSAP4) that achieved 100% accuracy in leave-one-out classification between patients and controls.
Conclusions: In this study, we have determined 11 differentially expressed genes, among which 4 where incorporated in a DFA model with high accuracy. Among these, BBS1, SUMO1 and RBBP4 are reported for the first time in MS.
References:
1. http://www.ncbi.nlm.nih.gov/pubmed/26254420
2. http://www.ncbi.nlm.nih.gov/pubmed/25215310
3. http://www.ncbi.nlm.nih.gov/geoprofiles/
Disclosure:
George Vavougios has nothing to disclose.
Eugenia Papachristopoulou has nothing to disclose.
Manolis Synadinakis has nothing to disclose.
Konstantinos Kormas has nothing to disclose.
Triantafyllos Doskas has nothing to disclose.
Abstract: EP1422
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - Genetics /Epigenetics and Pharmacogenetics
Background: Cellular mechanisms controlling cell death and proliferation play a crucial role in the pathogenesis of multiple sclerosis (MS). DJ-1/PARK7 is a multifunctional cytoprotective protein that has been reported to be upregulated in multiple sclerosis, both in brain samples and CSF versus controls. Furthermore, in a previous study, we derived a gene signature from the PARK7 interactome, implicated in histone deacetylation and chromatin remodeling processes in maliganant pleural mesothelioma (1) ; Epigenetic mechanisms have been shown to contribute to propagating autoreactivity in MS (2).
Goals: The objective of our study is to determine whether PARK7 and its network are differentially expressed in MS.
Methods: The GEOprofiles repository (3) was interrogated using the keywords “peripheral, blood, mononuclear, cells, park7”. Profile data (GSE21942 ) for a previously constructed PARK7 network (1) were downloaded. Differentially expressed genes (DEGs) were identified using independent samples t-test, as per the original GEOprofiles platform built-in analyses. Probes referring to the same gene were tested via the BLAST tool for sequence coverage (Human Genomic plus Transcript Database). Both mean (between-probe) and individual probe (post-BLAST verification) data were tested in a multivariate model employing stepwise linear discriminant function analysis (DFA). Gene ontology annotations were performed through the GENEmania tool.
Results: Gene expression profile GSE21942 data were downloaded form GEOprofiles in 17/4/16. Out of 13 genes, PARK7, SOD1, SUMO1, PIAS2, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7 and HSPA4 were differentially expressed in MS patients vs controls (p-value < 0.05). Stepwise linear discriminant function analysis (DFA) constructed a predictive model (Wilk"s λ=0.117, χ2=53.683, p=6.1314e-11) with 4 coefficients (BBS1, SUMO1, RBBP4, HSAP4) that achieved 100% accuracy in leave-one-out classification between patients and controls.
Conclusions: In this study, we have determined 11 differentially expressed genes, among which 4 where incorporated in a DFA model with high accuracy. Among these, BBS1, SUMO1 and RBBP4 are reported for the first time in MS.
References:
1. http://www.ncbi.nlm.nih.gov/pubmed/26254420
2. http://www.ncbi.nlm.nih.gov/pubmed/25215310
3. http://www.ncbi.nlm.nih.gov/geoprofiles/
Disclosure:
George Vavougios has nothing to disclose.
Eugenia Papachristopoulou has nothing to disclose.
Manolis Synadinakis has nothing to disclose.
Konstantinos Kormas has nothing to disclose.
Triantafyllos Doskas has nothing to disclose.