Similar Datasets
Project description:The availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need to identify reliable biomarkers to monitor disease progression, therapeutic response and classify patients according to disease severity. Objectives of this study were to identify potential biomarkers for disease severity, and to describe changes in the proteomic profile after 302 days of nusinersen administration (T302). In this multicenter retrospective longitudinal study, we employed an untargeted non-targeted mass spectrometry-based proteomic approach (LC-MS) on cerebrospinal fluid (CSF) samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at baseline and T302. A machine learning classifier approach (Random Forest, RF) was applied to exploit proteins able to stratify disease severity at baseline. Bioinformatics analysis was performed to investigate Gene Ontology (GO) functional annotation of differentially expressed proteins (DEPs) at T302. The RF algorithm identified CNTN1 and NRXN3 as new potential biomarkers of disease severity based on their expression at baseline. Analysis of changes in proteomic profiles identified 147 DEPs after nusinersen treatment in SMA1, 135 in SMA2, and 289 in SMA3. Overall, Nusinersen-induced changes on proteomic profile were consistent with i) common effects observed in all SMA types (i.e. regulation of axonogenesis), and ii) disease severity-specific changes, namely regulation of glucose metabolism in SMA1, of coagulation processes in SMA2, and of complement cascade in SMA3. By analyzing a large cohort of CSF samples from SMA patients, and applying cutting-edge bioinformatic analysis and artifical intelligence alghorithms, this study has identified new potential biomarkers of disease severity, and provided new insights on biological processes modulation after 302 days of nusinersen treatment.
2024-10-02 | PXD047529 | Pride
Project description:Sequencing of Newborn Blood spot DNA to Improve and Expand Newborn Screening (NBSeq)
| PRJNA826607 | ENA
Project description:Sequencing of Newborn Blood spot DNA to Improve and Expand Newborn Screening (NBSeq)
| PRJNA671386 | ENA
Project description:Newborn screening blood spots were obtained for neonates born to women enrolled in the Emory University African American Microbiome in Pregnacy Cohort
2021-07-01 | GSE154446 | GEO
Project description:modENCODE_submission_3228 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP130(official name : OP130 genotype : unc119(ed3);wgIs130(sma-9::TY1 EGFP FLAG C;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The SMA-9::EGFP fusion protein is expressed in the correct sma-9 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the SMA-9 transcription factor. made_by : S Kim ); Developmental Stage: L2; Genotype: unc119(ed3);wgIs130(sma-9::TY1 EGFP FLAG C;unc119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L2; Target gene sma-9; Strain OP130(official name : OP130 genotype : unc119(ed3);wgIs130(sma-9::TY1 EGFP FLAG C;unc119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The SMA-9::EGFP fusion protein is expressed in the correct sma-9 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the SMA-9 transcription factor. made_by : S Kim ); temp (temperature) 20 degree celsius
2013-07-11 | E-GEOD-48700 | biostudies-arrayexpress
Project description:North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS)
| PRJNA827226 | ENA
Project description:North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS)
| PRJNA671191 | ENA
Project description:DNA samples were derived from dried blood spots taken for newborn screening when infants were several days of age, after obtaining permission from the participants when they were aged 18 years, or from their parents if they were younger than 18 years.
2016-04-18 | GSE80283 | GEO
Project description:Background: Severe combined immunodeficiency (SCID) is characterized by arrested T lymphocyte production and B lymphocyte dysfunction, resulting in life-threatening infections. Early diagnosis of SCID through population-based newborn screening (NBS) optimizes clinical management and outcomes, and also permits identification of previously unknown factors essential for human lymphocyte development. Methods: SCID was detected, prior to onset of infections, by NBS of T cell receptor excision circles, a biomarker for thymic output. Upon confirmation, the affected baby was treated by allogeneic hematopoietic cell transplantation (HCT). The genetic cause was sought by exome sequencing of the patient and parents, followed by functional analysis of a prioritized candidate gene using human hematopoietic stem cells (HSC) and zebrafish embryos. Results: An infant with leaky SCID, craniofacial and dermal abnormalities, and absent corpus callosum had his immune deficit fully corrected by HCT. Exome sequencing revealed a heterozygous, de novo, missense mutation pN441K in BCL11B. The mutant Bcl11b protein had dominant negative activity, abrogating the ability of wild type Bcl11b to bind DNA, arresting T cell lineage development and disrupting HSC migration, revealing a novel function of Bcl11b. The patientâs defects, recapitulated in Bcl11b-deficient zebrafish, were reversed by ectopic expression of intact, but not mutant, human BCL11B. Conclusions: Newborn screening facilitated treatment and identification of a novel etiology for human SCID. Coupling exome sequencing with candidate gene evaluation in human HSC and in zebrafish revealed that a constitutional BCL11B mutation causes human multisystem anomalies with SCID, while also revealing a novel, pre-thymic role for Bcl11b in hematopoietic progenitors. 3 samples were analyzed in duplicate, Sample 1 was human HSC transduced with GFP only lentivirus which served as controls, Sample 2 was human HSC transduced with lentivirus expressing FLAG-tagged WT BCL11B and GFP, Sample 3 was human HSC transduced with lentivirus expressing FLAG-tagged mutant BCL11B and GFP
2016-07-29 | E-GEOD-84941 | biostudies-arrayexpress