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GSE103225

GSE GEO
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Transcriptome-pathology correlations predict CSNK1E-mediated TDP-43 phosphorylation in sporadic amyotrophic lateral sclerosis

Organism: Homo sapiens
Platform: GPL20301
Samples: 10
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Aug 29 2017
Last Updated: Jul 25 2021
Status: Public on Jun 06 2018
Contact: Gene,,Yeo (UCSD)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA400580 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP116386

Summary

Sporadic amyotrophic lateral sclerosis (sALS) is the most common (~90%) form of ALS. There are no animal models of sALS and exact molecular mechanisms remain elusive. Here, we elucidate gene-expression profiles in laser capture microdissected enriched surviving motor neurons (MNs) from sALS lumbar spinal cords in patients who had rostral onset and caudal progression. A strong signature was detected and immunological signals were computationally filtered. The filtered dataset showed clustering groups that were significantly explained by levels of phosphorylated TDP-43 (pTDP-43). Transcriptome-pathology correlations and enhanced crosslinking and immunoprecipitation combined with sequencing (eCLIP-seq) identified that Casein kinase 1ε (CSNK1E) had the highest correlation with pTDP-43 status and TDP-43 binding in its 3’UTR. Furthermore, CSNK1E interacted with TDP-43 on protein level and its overexpression lead to increased cytoplasmic pTDP-43 accumulations in iPSC-MNs, suggesting CSNK1E directly mediates TDP-43 phosphorylation. Therefore, we report an essential framework for molecular disease classification and transcriptome – pathology correlation in sALS to identify candidate genes for elucidating disease mechanisms and potential therapeutic interventions.

Overall Design

eCLIP-seq was performed in for TDP-43 in two controls and three sALS patients. Each sample has a size-matched input control for analysis

Analysis (32 steps)

View Data Processing
Processing steps for GSE103225
  1. Takes output from raw files.
  2. Run to trim off both 5’ and 3’ adapters on both reads.
  3. Command: quality-cutoff 6 -m 18 -a NNNNNAGATCGGAAGAGCACACGTCTGAACTCCAGTCAC -g CTTCCGATCTACAAGTT -g CTTCCGATCTTGGTCCT -A AACTTGTAGATCGGA -A AGGACCAAGATCGGA -A ACTTGTAGATCGGAA -A GGACCAAGATCGGAA -A CTTGT AGATCGGAAG -A GACCAAGATCGGAAG -A TTGTAGATCGGAAGA -A ACCAAGATCGGAAGA -A TGTAGATCGGAAGAG -A CCAAGATCGGAAGAG -A GTAGATCGGAAGAGC -A CAAGATCGGAAGAGC -A TAGATCGGAAGAGCG -A AAGATCGGAAGAGCG -A AGATCGGAAGAGCGT -A GATCGGAAGAGCGTC -A ATCGGAAGAGCGTCG -A TCGGAAGAGCGTCGT -A CGGAAGAGCGTCGTG -A GGAAGAGCGTCGTGT -o /full/path/to/files/file_R1.C01.fastq.gz.adapterTrim.fastq.gz -p /full/path/to/files/file_R2.C01.fastq.gz.adapterTrim.fastq.gz /full/path/to/files/file_R1.C01.fastq.gz /full/path/to/files/file_R2.C01.fastq.gz > /full/path/to/files/file_R1.C01.fastq.gz.adapterTrim.metrics
  4. Takes output from cutadapt round 1.
  5. Run to trim off the 3’ adapters on read 2, to control for double ligation events.
  6. Command: cutadapt -f fastq --match-read-wildcards --times 1 -e 0.1 -O 5 --quality-cutoff 6 -m 18 -A AACTTGTAGATCGGA -A AGGACCAAGATCGGA -A ACTTGTAGATCGGAA -A GGACCAAGATCGGAA -A CTTGTAGATCGGAAG -A GACCAAGATCGGAAG -A TTGTAGATCGGAAGA -A ACCAAGATCGGAAGA -A TGTAGATCGGAAGAG -A CCAAGATCGGAAGAG -A GTAGATCGGAAGAGC -A CAAGATCGGAAGAGC -A TAGATCGGAAGAGCG -A AAGATCGGAAGAGCG -A AGATCGGAAGAGCGT -A GATCGGAAGAGCGTC -A ATCGGAAGAGCGTCG -A TCGGAAGAGCGTCGT -A CGGAAGAGCGTCGTG -A GGAAGAGCGTCGTGT -o /full/path/to/files/file_R1.C01.fastq.gz.adapterTrim.round2.fastq.gz -p /full/path/to/files/file_R2.C01.fastq.gz.adapterTrim.round2.fastq.gz /full/path/to/files/file_R1.C01.fastq.gz.adapterTrim.fastq.gz /full/path/to/files/file_R2.C01.fastq.gz.adapterTrim.fastq.gz > /full/path/to/files/file_R1.C01.fastq.gz.adapterTrim.round2.metrics
  7. Takes output from cutadapt round 2.
  8. Maps to human specific version of RepBase used to remove repetitive elements, helps control for spurious artifacts from rRNA (& other) repetitive reads.
Showing first 8 steps.

Supplementary Files (1)

GSE103225_RAW.tar Download
GEO Samples (10)
GSM2758478 GSM2758479 GSM2758480 GSM2758481 GSM2758482 GSM2758483 GSM2758484 GSM2758485 GSM2758486 GSM2758487

Dataset Citations (1)

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
PMID 29881994 · 2018 · Acta neuropathologica
Florian Krach, Ranjan Batra, Emily C Wheeler, Anthony Q Vu, Ruth Wang, Kasey Hutt, Stuart J Rabin, Michael W Baughn, Ryan T Libby, Sandra Diaz-Garcia, Jennifer Stauffer, Elaine Pirie, Shahram Saberi, Maria Rodriguez, Assael A Madrigal, Zacharias Kohl, Beate Winner, Gene W Yeo, John Ravits

SRA Experiments (10) and Runs (10)

Total: 9171 MB
SRX3143965 SRP116386 RIP-Seq PAIRED
GSM2758478: control_4_IP; Homo sapiens; RIP-Seq
Sample: SRS2476536
BioProject: PRJNA400580
BioSample: SAMN07571476
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
antibody: TDP-43
antibody manufacturer: Bethyl
in-line barcodes: A01=AAGCAAT; B06=GGCTTGT
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988190 22070590 2427764900 888.45 RB_CTRL4_IP_S68_L007_R1_001.fastq.gz, RB_CTRL4_IP_S68_L007_R2_001.fas… SRA
SRX3143966 SRP116386 RIP-Seq PAIRED
GSM2758479: control_39_IP; Homo sapiens; RIP-Seq
Sample: SRS2476537
BioProject: PRJNA400580
BioSample: SAMN07571475
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
antibody: TDP-43
antibody manufacturer: Bethyl
in-line barcodes: A01=AAGCAAT; B06=GGCTTGT
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988191 21624720 2378719200 863.08 RB_CTRL39_IP_S70_L007_R1_001.fastq.gz, RB_CTRL39_IP_S70_L007_R2_001.f… SRA
SRX3143967 SRP116386 RIP-Seq PAIRED
GSM2758480: sALS_30_IP; Homo sapiens; RIP-Seq
Sample: SRS2476538
BioProject: PRJNA400580
BioSample: SAMN07571485
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
antibody: TDP-43
antibody manufacturer: Bethyl
in-line barcodes: C01=ACAAGTT; D08=TGGTCCT
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988192 25420047 2796205170 1026.2 RB_sALS30_IP_S72_L007_R1_001.fastq.gz, RB_sALS30_IP_S72_L007_R2_001.f… SRA
SRX3143968 SRP116386 RIP-Seq PAIRED
GSM2758481: sALS_32_IP; Homo sapiens; RIP-Seq
Sample: SRS2476539
BioProject: PRJNA400580
BioSample: SAMN07571484
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
antibody: TDP-43
antibody manufacturer: Bethyl
in-line barcodes: C01=ACAAGTT; D08=TGGTCCT
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988193 21810963 2399205930 858.97 RB_sALS32_IP_S76_L007_R1_001.fastq.gz, RB_sALS32_IP_S76_L007_R2_001.f… SRA
SRX3143969 SRP116386 RIP-Seq PAIRED
GSM2758482: sALS_33_IP; Homo sapiens; RIP-Seq
Sample: SRS2476540
BioProject: PRJNA400580
BioSample: SAMN07571483
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
antibody: TDP-43
antibody manufacturer: Bethyl
in-line barcodes: C01=ACAAGTT; D08=TGGTCCT
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988194 19441086 2138519460 775.63 RB_sALS33_IP_S78_L007_R1_001.fastq.gz, RB_sALS33_IP_S78_L007_R2_001.f… SRA
SRX3143970 SRP116386 RIP-Seq PAIRED
GSM2758483: control_4_Input; Homo sapiens; RIP-Seq
Sample: SRS2476541
BioProject: PRJNA400580
BioSample: SAMN07571482
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988195 28710006 3158100660 1171.66 RB_CTRL4_INPUT_S67_L007_R1_001.fastq.gz, RB_CTRL4_INPUT_S67_L007_R2_0… SRA
SRX3143971 SRP116386 RIP-Seq PAIRED
GSM2758484: control_39_Input; Homo sapiens; RIP-Seq
Sample: SRS2476543
BioProject: PRJNA400580
BioSample: SAMN07571481
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988196 22182557 2440081270 903.76 RB_CTRL39_INPUT_S69_L007_R1_001.fastq.gz, RB_CTRL39_INPUT_S69_L007_R2… SRA
SRX3143972 SRP116386 RIP-Seq PAIRED
GSM2758485: sALS_30_Input; Homo sapiens; RIP-Seq
Sample: SRS2476542
BioProject: PRJNA400580
BioSample: SAMN07571480
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988197 23167191 2548391010 942.74 RB_sALS30_INPUT_S71_L007_R1_001.fastq.gz, RB_sALS30_INPUT_S71_L007_R2… SRA
SRX3143973 SRP116386 RIP-Seq PAIRED
GSM2758486: sALS_32_Input; Homo sapiens; RIP-Seq
Sample: SRS2476544
BioProject: PRJNA400580
BioSample: SAMN07571479
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988198 22367184 2460390240 906.83 RB_sALS32_INPUT_S75_L007_R1_001.fastq.gz, RB_sALS32_INPUT_S75_L007_R2… SRA
SRX3143974 SRP116386 RIP-Seq PAIRED
GSM2758487: sALS_33_Input; Homo sapiens; RIP-Seq
Sample: SRS2476545
BioProject: PRJNA400580
BioSample: SAMN07571478
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human frontal cortex
tissue: frontal cortex
Original files (1)
human frontal cortex
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR5988199 20655957 2272155270 833.92 RB_sALS33_INPUT_S77_L007_R1_001.fastq.gz, RB_sALS33_INPUT_S77_L007_R2… SRA

Linked Publications (1)

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
Acta neuropathologica · 2018

Data Files (14)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— RB_CTRL39_INPUT_S69_L007_R1_001.fastq.gz RIP-Seq 903.8 MB link
— RB_CTRL39_IP_S70_L007_R1_001.fastq.gz RIP-Seq 863.1 MB link
— RB_CTRL4_INPUT_S67_L007_R1_001.fastq.gz RIP-Seq 1.1 GB link
— RB_CTRL4_IP_S68_L007_R1_001.fastq.gz RIP-Seq 888.4 MB link
— RB_CTRL4_IP_S68_L007_R2_001.fastq.gz RIP-Seq 888.4 MB link
— RB_sALS30_INPUT_S71_L007_R1_001.fastq.gz RIP-Seq 942.7 MB link
— RB_sALS30_IP_S72_L007_R1_001.fastq.gz RIP-Seq 1.0 GB link
— RB_sALS32_INPUT_S75_L007_R1_001.fastq.gz RIP-Seq 906.8 MB link
— RB_sALS32_IP_S76_L007_R1_001.fastq.gz RIP-Seq 859.0 MB link
— RB_sALS33_INPUT_S77_L007_R1_001.fastq.gz RIP-Seq 833.9 MB link
— RB_sALS33_IP_S78_L007_R1_001.fastq.gz RIP-Seq 775.6 MB link
— SRR5988191 RIP-Seq 863.1 MB link
— SRR5988194 RIP-Seq 775.6 MB link
— SRR5988199 RIP-Seq 833.9 MB link