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Whole-transcriptome analysis in peripheral blood mononuclear cells from patients with lipid-specific oligoclonal IgM band characterization reveals two circular RNAs and two linear RNAs as biomarkers of highly active disease

ABSTRACT: Whole-transcriptome analysis in peripheral blood mononuclear cells from patients with lipid-specific oligoclonal IgM band characterization reveals two circular RNAs and two linear RNAs as biomarkers of highly active disease

PROVIDER: PRJNA667461 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12774644_1.fastq.gz	Fastqsanger.gz
	SRR12774644_2.fastq.gz	Fastqsanger.gz
	SRR12774645_1.fastq.gz	Fastqsanger.gz
	SRR12774645_2.fastq.gz	Fastqsanger.gz
	SRR12774646_1.fastq.gz	Fastqsanger.gz

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Whole-transcriptome analysis in peripheral blood mononuclear cells from patients with lipid-specific oligoclonal IgM band characterization reveals two circular RNAs and two linear RNAs as biomarkers of highly active disease

Project description:Background: The presence of anti-myelin lipid specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in PBMCs from patients with lipid-specific oligoclonal IgM band characterization. Methods: We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. Results: RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (IRF5 and MTRNR2L8) are downregulated in PBMCs from patients with positive LS-OCMBs. Finally, those RNAs show a performance of a 70% accuracy in some of the combinations. Conclusion: The expression of hsa_circ_0000478, hsa_circ_0116639, IRF5 and MTRNR2L8 might serve as minimally invasive biomarkers of highly active disease.

2020-12-21 | GSE159035 | GEO

Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease.

Project description:The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in peripheral blood mononuclear cells (PBMCs) from patients with lipid-specific oligoclonal IgM band characterization. We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (IRF5 and MTRNR2L8) are downregulated in PBMCs from patients with positive LS-OCMBs. Finally, those RNAs show a performance of a 70% accuracy in some of the combinations. The expression of hsa_circ_0000478, hsa_circ_0116639, IRF5 and MTRNR2L8 might serve as minimally invasive biomarkers of highly active disease.

| S-EPMC7759842 | biostudies-literature

Whole-transcriptome in PBMCs from patients with LS-OCMB characterization reveals 4 RNAs as biomarkers of highly active disease

2020-12-21 | GSE159033 | GEO

Identification of target antigens of CSF OCB-derived monoclonal antibodies

Project description:The identification of target antigens recognized by monoclonal antibodies that have been derived from oligoclonal band IgG of CSF samples from multiple sclerosis patients.

2016-06-06 | GSE72789 | GEO

Comparative analysis of miRNA expression during the development of insects of different metamorphosis modes and germ-band types

Project description:Do miRNAs contribute to specify the germ-band type and the body structure in the insect embryo? Our goal was to address that issue by studying the changes in miRNA expression along the ontogeny of the German cockroach Blattella germanica, which is a short germ-band and hemimetabolan species. We sequenced small RNA libraries representing 11 developmental stages of B. germanica ontogeny (with especial emphasis on embryogenesis) and the changes in miRNA expression were examined. Data were compared with equivalent data for two long germ-band holometabolan species Drosophila melanogaster and Drosophila virilis, and the short germ-band holometabolan species Tribolium castaneum. The identification of B. germanica embryo small RNA sequences unveiled miRNAs not detected in previous studies, such as those of the MIR-309 family and 54 novel miRNAs. Four main waves of miRNA expression were recognized (with most miRNA changes occurring during the embryonic stages): the first from day 0 to day 1 of embryogenesis, the second during mid-embryogenesis (days 0-6), the third (with an acute expression peak) on day 2 of embryonic development, and the fourth during post-embryonic development. The second wave defined the boundaries of maternal-to-zygotic transition, with maternal mRNAs being cleared - presumably by Mir-309 and associated scavenger miRNAs. miRNAs follow well-defined patterns of expression over hemimetabolan ontogeny - patterns that are more diverse during embryonic development than during the nymphal stages. The results suggest that miRNAs play important roles in the developmental transitions between the embryonic stages of development (starting with maternal loading), during which they might influence the germ-band type and metamorphosis mode.

2017-10-23 | GSE87031 | GEO

25 kDa band from HSPA1A immunoprecipitation

Project description:HSPA1A was immunoprecipitated from WT and TorsinKO HeLa cells. A band around 27 kDa was identified uniquely in TorsinKO samples and for identification, this band was extracted.

2022-08-25 | PXD036266 | Pride

white band disease-infected Acropora cervicornis bacteria

Project description:Microbial communities of white band disease-infected Acropora cervicornis

| PRJNA391985 | ENA

Structure of examined circular RNAs and some of their linear cognate RNAs

Project description:Structure of examined circular RNAs and some of their linear cognate RNAs

| PRJNA521266 | ENA

Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle

Project description:Muscle contraction is driven by the molecular machinery of the sarcomere. While the constituent components of the sarcomere are well characterized, it is less clear how the activity and turnover of sarcomeric proteins is regulated. In particular, phosphorylation is critical regulator of muscle function. Thus, identification of regulatory kinases is key to understanding the sarcomere function. Pathogenic variants in alpha kinase 3 (ALPK3) cause cardiomyopathy and musculoskeletal disease, but little is known about this atypical kinase. Here we show that ALPK3 localizes to the M-Band of the sarcomere and define the ALPK3-dependent phosphoproteome. ALPK3 deficiency disrupted sarcomeric organization and calcium kinetics in hPSC-derived cardiomyocytes and reduced force generation in cardiac organoids. Phosphoproteomic profiling identified ALPK3-dependant phospho-peptides that were enriched for sarcomeric components of the M-band and the ubiquitin-binding protein SQSTM1. Analysis of the ALPK3 interactome confirmed binding to M-band proteins including SQSTM1. Importantly, in hPSC-derived cardiomyocytes modeling ALPK3 deficiency and cardiomyopathic ALPK3 mutations, sarcomeric organization and M-band localization of SQSTM1 were abnormal. These data suggest ALPK3 has an integral role in maintaining sarcomere integrity and proteostasis in striated muscle. We propose this mechanism may underly disease pathogenesis in patients with ALPK3 variants.

2023-01-10 | GSE215304 | GEO

Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins.

Project description:Oligoclonal Ig bands (OCBs) of the cerebrospinal fluid are a hallmark of multiple sclerosis (MS), a disabling inflammatory disease of the central nervous system (CNS). OCBs are locally produced by clonally expanded antigen-experienced B cells and therefore are believed to hold an important clue to the pathogenesis. However, their target antigens have remained unknown, mainly because it was thus far not possible to isolate distinct OCBs against a background of polyclonal antibodies. To overcome this obstacle, we copurified disulfide-linked Ig heavy and light chains from distinct OCBs for concurrent analysis by mass spectrometry and aligned patient-specific peptides to corresponding transcriptome databases. This method revealed the full-length sequences of matching chains from distinct OCBs, allowing for antigen searches using recombinant OCB antibodies. As validation, we demonstrate that an OCB antibody from a patient with an infectious CNS disorder, neuroborreliosis, recognized a Borrelia protein. Next, we produced six recombinant antibodies from four MS patients and identified three different autoantigens. All of them are conformational epitopes of ubiquitous intracellular proteins not specific to brain tissue. Our findings indicate that the B-cell response in MS is heterogeneous and partly directed against intracellular autoantigens released during tissue destruction. In addition to helping elucidate the role of B cells in MS, our approach allows the identification of target antigens of OCB antibodies in other neuroinflammatory diseases and the production of therapeutic antibodies in infectious CNS diseases.

| S-EPMC4948369 | biostudies-literature

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