NBDC Research ID: hum0488.v1
SUMMARY
Aims: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes systemic muscle weakness, dysphagia, and respiratory failure. Currently, there are no definitive cures available, and the development of new treatments is urgently needed. The causes of ALS remain largely unknown, but in most ALS patients, there is a mislocalization of the RNA-binding protein TDP-43 from the nucleus to the cytoplasm in motor neurons, along with its abnormal aggregation. This suggests that some abnormalities in RNA metabolism mediated by TDP-43 are related to the onset of ALS. This study aims to elucidate the significance of RNA metabolic abnormalities in ALS.
Methods: WGS, bulk RNA-seq, single-nucleus RNA-seq, single-nucleus ATAC-seq
Participants/Materials: 13 ALS patients whose autopsy pathology confirmed intracellular mislocalization and abnormal deposition of TDP-43 and 13 patients with other diseases who had no TDP-43 pathology (non-ALS) at Osaka University Hospital and Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology.
| Dataset ID | Type of Data | Criteria | Release Date |
|---|---|---|---|
| JGAS000851 | NGS (bulk RNA-seq) | Controlled-access (Type I) | 2026/01/05 |
| JGAS000852 | NGS (WGS, snRNA-seq, snATAC-seq) | Controlled-access (Type I) | 2026/01/05 |
*Data users need to apply an application for Using NBDC Human Data to reach the Controlled-access Data. Learn more
MOLECULAR DATA
| Participants/Materials: |
ALS (ICD10: G12.2): 7 cases non-ALS: 7 cases frozen medulla oblongata (pyramidal region) tissues |
| Targets | bulk RNA-seq |
| Target Loci for Capture Methods | - |
| Platform | MGI [DNBSEQ-G400] |
| Library Source | RNAs extracted from frozen samples |
| Cell Lines | - |
| Library Construction (kit name) | NEBNext rRNA Depletion Kit (Human/Mouse/Rat), SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian |
| Fragmentation Methods | - |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 100 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000993 |
| Total Data Volume | 147.9 GB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials: |
ALS (ICD10: G12.2): 6 cases non-ALS: 6 cases frozen brain (motor cortex) and spinal cord (lumber spinal cord L4 and L5) tissues |
| Targets | WGS |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | DNAs extracted from frozen samples |
| Cell Lines | - |
| Library Construction (kit name) | TruSeq DNA PCR-Free Kit |
| Fragmentation Methods | included in the above library construction kit |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 150 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000994 |
| Total Data Volume | 1.8 TB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials: |
ALS (ICD10: G12.2): 6 cases non-ALS: 6 cases frozen brain (motor cortex) and spinal cord (lumber spinal cord L4 and L5) tissues |
| Targets | snRNA-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | RNAs extracted from nuclei obtained from frozen samples |
| Cell Lines | - |
| Library Construction (kit name) | Chromium Next GEM Single Cell 3ʹ v3.1 |
| Fragmentation Methods | manufacturer's protocol |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 150 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000994 |
| Total Data Volume | 1.8 TB (fastq) |
| Comments (Policies) | NBDC policy |
| Participants/Materials: |
ALS (ICD10: G12.2): 4 cases non-ALS: 4 cases frozen brain (motor cortex) and spinal cord (lumber spinal cord L4 and L5) tissues |
| Targets | snATAC-seq |
| Target Loci for Capture Methods | - |
| Platform | Illumina [NovaSeq 6000] |
| Library Source | DNAs extracted from nuclei obtained from frozen samples |
| Cell Lines | - |
| Library Construction (kit name) | Chromium Next GEM Single Cell Multiome ATAC + Gene Expression |
| Fragmentation Methods | manufacturer's protocol |
| Spot Type | Paired-end |
| Read Length (without Barcodes, Adaptors, Primers, and Linkers) | 150 bp |
| Japanese Genotype-phenotype Archive Dataset ID | JGAD000994 |
| Total Data Volume | 1.8 TB (fastq) |
| Comments (Policies) | NBDC policy |
DATA PROVIDER
Principal Investigator: Seiichi Nagano
Affiliation: Department of Neurotherapeutics, Osaka University Graduate School of Medicine
Project / Group Name: -
Funds / Grants (Research Project Number):
| Name | Title | Project Number |
|---|---|---|
| KAKENHI Grant-in-Aid for Scientific Research (B) | Elucidation of the pathogenesis and development of the treatment strategy of ALS/FTLD focusing on the local translation in neuronal axons | 21H02841 |
| KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area) | Elucidation of the pathogenesis of amyotrophic lateral sclerosis based on neuronal iron metabolism disorders | 22H04811 |
| KAKENHI Grant-in-Aid for Challenging Research (Exploratory) | Elucidation of the mechanism of ALS onset via cell type-specific splicing alterations | 23K18265 |
| KAKENHI Grant-in-Aid for Scientific Research (B) | Identification of ALS pathology-related factors through integrated analysis of patient tissue-derived RNA-seq data | 24K02370 |
| Translational Research Program, Japan Agency for Medical Research and Development (AMED) | Development of a treatment for amyotrophic lateral sclerosis through improvement of ribosomal function within neurons | JP20lm0203007 |
| Practical Research Project for Rare / Intractable Diseases, Japan Agency for Medical Research and Development (AMED) | Development of a novel treatment for amyotrophic lateral sclerosis (ALS) aimed at improving ribosomal function | JP21ek0109520 |
| Brain and Mind Research Promotion Program, Japan Agency for Medical Research and Development (AMED) | Elucidation of pathogenesis mechanisms and development of therapeutic approaches for amyotrophic lateral sclerosis mediated by regulatory T cells | JP23wm0525029 |
| Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University | Elucidation of Pathogenesis and Development of Therapeutic Approaches for Amyotrophic Lateral Sclerosis (ALS) Centered on Endogenous Retroviruses (ERVs) | - |
PUBLICATIONS
| Title | DOI | Dataset ID | |
|---|---|---|---|
| 1 | piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis | doi: 10.1007/s12035-021-02686-2 | JGAD000993 |
| 2 | Alternative Splicing Alterations in Patients With Amyotrophic Lateral Sclerosis: Link to the Disruption of TAR DNA-Binding Protein 43 kDa Functions | doi: 10.1111/ncn3.12880 | JGAD000993 |
| 3 | Single-nucleus multiome shows motor neuron glutamate overactivation in amyotrophic lateral sclerosis | doi: 10.1093/brain/awaf426 | JGAD000994 |
USRES (Controlled-access Data)
| Principal Investigator | Affiliation | Country/Region | Research Title | Data in Use (Dataset ID) | Period of Data Use |
|---|---|---|---|---|---|
