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Lymphocyte gene expression data from moderate stage HD patients and controls

ABSTRACT: Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared to controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV et al. (2005) Proc Natl Acad Sci U S A 102: 11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies. Keywords: RNA biomarker screen

ORGANISM(S): Homo sapiens

PROVIDER: GSE8762 | GEO | 2007/08/15

SECONDARY ACCESSION(S): PRJNA102041

REPOSITORIES: GEO

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Lymphocyte gene expression data from moderate stage HD patients and controls

Project description:Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared to controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV et al. (2005) Proc Natl Acad Sci U S A 102: 11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies. Keywords: RNA biomarker screen Lymphocyte samples from 12 moderate stage HD patients (8 female and 4 male) and 10 age-matched controls (5 female and 5 male).

2007-08-15 | E-GEOD-8762 | biostudies-arrayexpress

Differential expression analysis of miRNAs expressed in blood and CSF of Huntington's disease [miRNA-seq]

Project description:Huntington’s disease (HD) is an autosomal-dominant neurodegenerative disorder caused by the CAG expansion in the Huntingtin (HTT) gene. Several studies have shown the potential of microRNAs as biomarkers in neurodegenerative diseases. However, no bona fide microRNAs have been identified as promising diagnostic biomarkers for HD. As part of the PREDICT-HD project, here we performed NanoString on blood samples of 115 pre-manifest HD cases and 111 controls in an effort to provide promising biomarkers for the diagnostic of HD or the disease processes tracking. The results showed that five miRNAs (miR-1252, miR-433, miR-553, miR-138-5p and miR-2053) are significantly differentially expressed in pre-manifest gene-positive HD cases vs. gene-negative controls. We also explored the miRNAs associated with HD severity by correlating the miRNA expression with CAP scores of 115 pre-manifest HD samples and found that 41 and 24 miRNAs are negatively and positively correlated with CAP scores significantly. Furthermore, target gene set of miR-138 and miR-433 , its co-expressed mRNAs in ROSMAP, and differentially expressed mRNAs of HD reveal four overlap genes (CASP7, CNOT6L, TMED and FERMT2). In summary, our study provides new insights into biomarker of Huntington’s disease by analyzing the cross-sectional miRNA expression data in blood.

2018-06-19 | GSE108396 | GEO

Differential expression analysis of miRNAs expressed in blood and CSF of Huntington's disease [miRNA array]

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Transcriptomics data of blood and brain from the YAC128 Huntington's disease mouse model [blood]

Project description:Therapeutic development for Huntington's disease (HD) would benefit from a method to monitor disease progression and treatment efficacy, ideally using blood biomarkers. Previously, HD-specific signatures were identified in human blood which adequately represented signatures in human brain, showing biomarker potential. Since drug candidates are normally first screened in rodent models, we aimed to identify HD-signatures in blood and brain of YAC128 HD mice and validate these with our previously identified human signatures. In both brain and blood, we identified HD-associated modules using Weighted Gene Co-expression Network Analysis (WGCNA) representing various biological processes previously associated with HD. Disease-related processes in blood and brain showed substantial overlap, including processes related to protein modification, cell cycle, RNA splicing, nuclear transport and vesicle-mediated transport. Moreover, the disease-associated processes shared between mouse blood and brain were highly comparable to those previously identified in human blood and brain. In addition to shared pathology, we identified HD-associated blood modules showing blood-specific pathology.

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Transcriptomics data of blood and brain from the YAC128 Huntington's disease mouse model [brain]

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The transcriptional modulator H2AFY marks Huntington's disease activity in men and mice

2011-09-01 | GSE24250 | GEO

Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood

Project description:In this study we investigated the suitability of blood to identify HD transcriptomic biomarkers, validated the outcome in an independent cohort and derived a first empiric panel of biomarkers capable of predicting HD motor scores. Finally we examined whether patient gene expression profiles could provide information about HD affected biological pathways. Examination of differentially expressed genes in peripheral whole blood using linear modelling of gene expression data (3 DGE) against UHDRS total motor scores of Huntington's Disease mutation carriers and controls.

2015-02-02 | E-GEOD-51799 | biostudies-arrayexpress

The transcriptional modulator H2AFY marks Huntington's disease activity in men and mice

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2011-09-01 | E-GEOD-24250 | biostudies-arrayexpress

IER3-AS1 interacting proteins by AP-MS

Project description:Characterisation IER3-AS1 interacting proteins using chromatin oligo-affinity precipitation (ChOP) followed by mass spectrometry. The HeLa cell lysates was incubated with biotinylated antisense oligonucleotides (ASO), targeting an experimental target antisense long noncoding RNA IER3-AS1 or a control RNA LacZ. LacZ and IER3-AS1 interacting proteomes were pulldown using Streptavidin beads. The eluted protein samples from both LacZ control ASOs and IER3-AS1 ASOs subjected to mass-spectrometry analyses to identify IER3-AS1 interacting proteins.

2022-10-15 | PXD035704 | Pride

Acute and chronic liver injury change the small RNA cargoes carried by serum small extracellular vesicles in mice

Project description:Compared to whole serum miRNAs, miRNAs in serum small extracellular vesicles (sEVs) are well protected form RNA enzymes, thus provide a consistent source of miRNA for disease biomarker detection. Serum sEVs and their miRNA cargos released by injured liver cells could be promising biomarkers for diagnosis of liver diseases. We were very interested to find out the effects of liver injury on serum extracellular vesicles as well as the small RNA components they transported, if there is any difference between acute and chronic injury. Study in this regard will help us to identify new serum biomarkers for liver injury, and to find out if there are specific markers for acute or chronic liver injury. To identify potential biomarker for liver injury based on serum sEVs miRNAs, we established the carbon tetrachloride (CCL4) induced acute and chronic liver injury mice model, and examined the dynamic changes of small RNA components, especially miRNAs, in serum sEVs.

2021-08-07 | E-MTAB-9462 | biostudies-arrayexpress

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