Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression from embryoid bodies derived from HBG3 HB9 ES cells exposed to serum from mice carrying an ALS causing mutation, or non-carrier littermates.

ABSTRACT: We have established proof of principle for the Indicator Cell Assay PlatformÈ (iCAPÈ), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patientsê blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, cost-effective disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value=3.81E-6) and correctly identified samples from a murine Huntingtonês disease model as non-carriers of ALS. In a preliminary human disease assay, the iCAP detected early stage Alzheimerês disease with 72% cross-validated accuracy (p-Value=3.10E-3). For both assays, iCAP features were enriched for disease-related genes, supporting the assayês relevance for disease research.

ORGANISM(S): Mus musculus

PROVIDER: GSE95659 | GEO | 2017/03/17

SECONDARY ACCESSION(S): PRJNA377854

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression from embryoid bodies derived from HBG3 HB9 ES cells exposed to serum from a murine Huntington's disease model

Project description:We have established proof of principle for the Indicator Cell Assay Platformé (iCAPé), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients' blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, cost-effective disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value=3.81E-6) and correctly identified samples from a murine Huntington's disease model as non-carriers of ALS. In a preliminary human disease assay, the iCAP detected early stage Alzheimer's disease with 72% cross-validated accuracy (p-Value=3.10E-3). For both assays, iCAP features were enriched for disease-related genes, supporting the assay's relevance for disease research.

2017-03-17 | GSE95842 | GEO

Gene expression from iPS derived neurons exposed to plasma from Alzheimer's (AD), pre-symptomatic AD, or control patients.

Project description:We have established proof of principle for the Indicator Cell Assay Platformé (iCAPé), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patientsÕ blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, cost-effective disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value=3.81E-6) and correctly identified samples from a murine HuntingtonÕs disease model as non-carriers of ALS. In a preliminary human disease assay, the iCAP detected early stage AlzheimerÕs disease with 72% cross-validated accuracy (p-Value=3.10E-3). For both assays, iCAP features were enriched for disease-related genes, supporting the assayÕs relevance for disease research.

2017-03-17 | GSE95810 | GEO

RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: considerations for biomarker discovery

Project description:Aim: Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether biomarkers for diagnosis, prognosis or cohort stratification could be identified by RNA sequencing (RNA-seq) of ALS patient peripheral blood. Methods: Whole blood RNA-seq data were generated for 96 Australian sporadic ALS (sALS) cases and 48 healthy controls (NCBI GEO accession GSE234297). Differences in sALS-control gene expression, transcript usage and predicted leukocyte proportions were assessed, with pathway analysis used to predict the activity state of biological processes. Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms were applied to search for diagnostic and prognostic gene expression patterns. Unsupervised clustering analysis was employed to determine whether sALS patient subgroups could be detected. Results: 245 differentially expressed genes were identified in sALS patients relative to controls, with enrichment of immune, metabolic and stress related pathways. sALS patients also demonstrated switches in transcript usage across a small set of genes. We established a classification model that distinguished sALS from controls with an accuracy of 78% (sensitivity: 79%, specificity: 75%) using the expression of 20 genes. Clustering analysis identified four patient subgroups with gene expression signatures and immune cell proportions reflective of distinct peripheral effects. Conclusions: Our findings suggest that peripheral blood RNA-seq can identify diagnostic biomarkers and distinguish molecular subtypes of sALS patients however, its prognostic value requires further investigation.

2023-10-12 | GSE234297 | GEO

Modifying macrophages at the periphery has the capacity to change microglial reactivity and increase ALS survival

Project description:Microglia and peripheral macrophages, combined, have been implicated in the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but without discriminating their respective roles. We now show that macrophages along peripheral motor neuron axons of ALS mice and patients react to neurodegeneration. In ALS mice, peripheral myeloid cell infiltration into the spinal cord was limited and disease duration dependent. Targeted gene modulation of the reactive oxygen species pathway in peripheral myeloid cells of ALS mice, using cell replacement, reduced both peripheral macrophage and microglial activation, delayed symptoms and increased ALS mouse survival. Transcriptomics revealed that sciatic nerve macrophages and microglia reacted very different to neurodegeneration, with abrupt temporal changes in macrophages and progressive, unidirectional activation in microglia. Modifying peripheral macrophages suppressed proinflammatory microglial responses, with a strong shift towards neuronal support. Thus, modifying macrophages at the periphery has the capacity to influence disease progression and is of therapeutic value for ALS.

2020-10-19 | GSE156202 | GEO

NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects

Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic ALS (n=8), MS (n=8) and HC (n=8) subjects. RNA was profiled using the NanoString nCounter miRNA expression assay

2012-07-25 | E-GEOD-39643 | biostudies-arrayexpress

Rio de la Plata Estuary: 16S rRNA amplicon sequence data

Project description:Bacterioplankton composition as indicator of environmental status: proof of principle using indicator value analysis of estuarine communities

| PRJEB29989 | ENA

RNAseq of fluidically isolated human and mouse motor neuron somas and axons in vitro

Project description:Spinal motor axons traverse large distances to innervate target muscle, and thus require local control of cellular events for proper functioning of the distal axon. To interrogate axon-specific processes we developed Axon-seq, a refined method incorporating microfluidic devices and stringent bioinformatic quality controls. Axon-seq demonstrates improved sensitivity and accuracy in whole-transcriptome sequencing of axons compared to previously published studies. Importantly, we show that axon transcriptomes are distinct from those of somas, displaying fewer detected genes and no contaminating astrocytic markers. We identified >5,000 transcripts in stem cell-derived spinal motor axons required for local oxidative energy production and ribosome generation. Axons contained unique transcription factor mRNAs, e.g. Ybx1, with implications for local axonal functions. Cross-comparison with existing mouse motor axon datasets, as well as our own human motor axon data identified a common axon transcriptome. As motor axons degenerate in amyotrophic lateral sclerosis (ALS), we investigated their response to the disease-causing SOD1G93A mutation, identifying 121 ALS-dysregulated transcripts. Several of these are implicated in axonal and dendritic outgrowth, including Nrp1, Dbn1, and Nek1, a known ALS-causing gene. In conclusion, Axon-seq proves a robust and improved method for RNA-seq of axons, furthers our understanding of peripheral axon biology, and identifies novel therapeutic targets to maintain neural connectivity in disease.

2018-12-11 | GSE121069 | GEO

Transcription profiling of human blood from patients with ALS vs healthy

Project description:ALS whole blood samples or non diseased control whole blood samples hybridized to HgU133vII Affymetrix genechips. As a factor value for experiment clinical history has been used including: 1) the ALS FRS score that provides a physician-generated estimate of the patientâs degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALS FRS score includes ten questions that ask the physician to rate his/her impression of the patients level of functional impairment in performing one of ten common tasks, e.g. climbing stairs. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 40=best. And 2) Forced Vital capacity that is the maximum amount of air a person can expel from the lungs after a maximum inspiration. It is equal to the inspiratory reserve volume plus the tidal volume plus the expiratory reserve volume. The measurement is performed during forceful exhalation. It reports the largest value of three technically satisfactory maneuvers. The three FVC measures should not differ by more than 150 mL from the next largest FVC, or 100 mL if the FVC is 1.0 L. If the difference is larger up to 8 measures should be performed.The percentage value is that compared to normal individuals of the same age and gender. 3) Date onset

2010-12-31 | E-TABM-940 | biostudies-arrayexpress

Long non-coding and coding RNAs characterization in Peripheral Blood Mononuclear Cells and Spinal Cord from Amyotrophic Lateral Sclerosis patients

Project description:Alteration in RNA metabolism, concerning both coding and long non-coding RNAs (lncRNAs), may play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed RNA-seq analysis to investigate, in Peripheral Blood Mononuclear Cells (PBMC) and spinal cord tissues, the regulation of non-coding and coding RNAs in Sporadic ALS patients (SALS), ALS mutated (FUS, TARDBP and SOD1) patients and matched controls. A total of 293 differentially expressed (DE) lncRNAs were found in SALS patients, as instead a limited amount of lncRNAs was found deregulated in mutated patients. Out of 87 mRNAs detected as differentially expressed in SALS patients, the 10 most differentially expressed were down-regulated and associated to transcription regulation, immunity and apoptosis pathways. 2 Taken together our data highlighted the importance, for the understanding of ALS disease, of extending the knowledge on transcriptome molecular alterations and on the significance in the disease of the classes of regulatory lncRNAs. Our data brought the light on the importance of lncRNAs and mRNAs regulation in central and peripheral systems, offering starting points for new investigations about pathogenic mechanism involved in ALS disease.

2018-04-22 | GSE106443 | GEO

miRNA profile in SOD-155 microglia

Project description:Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155. Total RNA was isolated from FACS sorted adult FCRLS+ microglia from spinal cords and Ly6CHi splenic monocytes from Non-Tg/miR155+/-, SOD1G93A-miR155+/- and SOD1G93A-miR155–/- mice at the age of 120d. Total RNA was extracted using mirVanaTM miRNA isolation kit (Ambion) according to the manufacturer’s protocol. nCounter Nansotring Mouse miRNA Assay Kit was used for miRNA expression profile

2014-11-24 | E-GEOD-52668 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data