GSE107895
GSE GEOWidespread RNA editing dysregulation in Autism Spectrum Disorders [eCLIP-seq]
Organism:
Homo sapiens
Platform:
GPL20301
Samples:
8
Experiment Types:
Expression profiling by high throughput sequencing
Submitted:
Dec 11 2017
Last Updated:
May 15 2019
Status:
Public on Dec 14 2018
Contact:
Grace,,Xiao (UCLA)
Relations
SubSeries of: GSE107896
BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA421898
SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP126484
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation.
Overall Design
eCLIP-seq in HepG2 and K562 Cells
Analysis (32 steps)
View Data Processing
Processing steps for GSE107895
- Takes output from raw files.
- Run to trim off both 5â and 3â adapters on both reads.
- 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
- Takes output from cutadapt round 1.
- Run to trim off the 3â adapters on read 2, to control for double ligation events.
- 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
- Takes output from cutadapt round 2.
- 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)
GSE107895_RAW.tar
Download
GEO Samples (8)
Dataset Citations (1)
Widespread RNA editing dysregulation in brains from autistic individuals.
PMID 30559470
· 2019
· Nature neuroscience
Stephen S Tran, Hyun-Ik Jun, Jae Hoon Bahn, Adel Azghadi, Gokul Ramaswami, Eric L Van Nostrand, Thai B Nguyen, Yun-Hua E Hsiao, Changhoon Lee, Gabriel A Pratt, Verónica Martínez-Cerdeño, Randi J Hagerman, Gene W Yeo, Daniel H Geschwind, Xinshu Xiao
SRA Experiments (8) and Runs (8)
Total: 8181 MBGSM2883063: FXR_Rep1; Homo sapiens; RIP-Seq
Sample: SRS2749218
BioProject: PRJNA421898
BioSample: SAMN08159809
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: A04,F05
antibody: FXR1
antibody manufacturer: Bethyl
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365478 | 2148698 | 434036996 | 227.31 | XiaoCollab1-5079_IP.R1.fastq.gz, XiaoCollab1-5079_IP.R2.fastq.gz, SRR… | SRA |
GSM2883064: FXR_Rep1_Input; Homo sapiens; RIP-Seq
Sample: SRS2749225
BioProject: PRJNA421898
BioSample: SAMN08159808
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: Ril19
antibody: FXR1
antibody manufacturer: Bethyl
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365479 | 31518926 | 3183411526 | 3009.66 | fix_FXR_In_D501_L000_R1_001.unassigned.barcoded.fastq.gz, fix_FXR_In_… | SRA |
GSM2883065: FXR_Rep2; Homo sapiens; RIP-Seq
Sample: SRS2749219
BioProject: PRJNA421898
BioSample: SAMN08159807
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: A03,G07
antibody: FXR1
antibody manufacturer: Bethyl
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365480 | 1856029 | 374917858 | 199.67 | XiaoCollab2-5352_IP.R1.fastq.gz, XiaoCollab2-5352_IP.R2.fastq.gz, SRR… | SRA |
GSM2883066: FXR_Rep2_Input; Homo sapiens; RIP-Seq
Sample: SRS2749220
BioProject: PRJNA421898
BioSample: SAMN08159806
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: Ril19
antibody: FXR1
antibody manufacturer: Bethyl
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365481 | 35679674 | 3603647074 | 3422.53 | fix_FXR_In_D502_701_L000_R1_001.unassigned.barcoded.fastq.gz, fix_FXR… | SRA |
GSM2883067: FMR_Rep1; Homo sapiens; RIP-Seq
Sample: SRS2749221
BioProject: PRJNA421898
BioSample: SAMN08159805
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: A01,B06
antibody: FMR1
antibody manufacturer: MBL
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365482 | 1791566 | 197072260 | 72.17 | TBN_51.R1.fastq.gz, TBN_51.R2.fastq.gz, SRR6365482, SRR6365482.sralite | SRA |
GSM2883068: FMR_Rep1_Input; Homo sapiens; RIP-Seq
Sample: SRS2749224
BioProject: PRJNA421898
BioSample: SAMN08159804
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: Ril19
antibody: FMR1
antibody manufacturer: MBL
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365483 | 28215874 | 1551873070 | 566.78 | TBN_50_S37_L003_R1_001.unassigned.barcoded.fastq.gz, TBN_50_S37_L003_… | SRA |
GSM2883069: FMR_Rep2; Homo sapiens; RIP-Seq
Sample: SRS2749222
BioProject: PRJNA421898
BioSample: SAMN08159803
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: A03,G07
antibody: FMR1
antibody manufacturer: MBL
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365484 | 3251055 | 357616050 | 131.46 | TBN_55.R1.fastq.gz, TBN_55.R2.fastq.gz, SRR6365484, SRR6365484.sralite | SRA |
GSM2883070: FMR_Rep2_Input; Homo sapiens; RIP-Seq
Sample: SRS2749223
BioProject: PRJNA421898
BioSample: SAMN08159802
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: human brain
barcodes: Ril19
antibody: FMR1
antibody manufacturer: MBL
tissue: Brain
rnase i fragmentation condition: 40 U
Original files (1)
human brain
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR6365485 | 27374174 | 1505579570 | 551.49 | TBN_54_S41_L003_R1_001.unassigned.barcoded.fastq.gz, TBN_54_S41_L003_… | SRA |
Linked Publications (1)
Widespread RNA editing dysregulation in brains from autistic individuals.
Nature neuroscience · 2019
Data Files (8)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | fix_FXR_In_D501_L000_R1_001.unassigned.barcoded.fastq.… | RIP-Seq | 2.9 GB | link | |||
| — | fix_FXR_In_D502_701_L000_R1_001.unassigned.barcoded.fa… | RIP-Seq | 3.3 GB | link | |||
| — | TBN_50_S37_L003_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 566.8 MB | link | |||
| — | TBN_51.R1.fastq.gz | RIP-Seq | 72.2 MB | link | |||
| — | TBN_54_S41_L003_R1_001.unassigned.barcoded.fastq.gz | RIP-Seq | 551.5 MB | link | |||
| — | TBN_55.R1.fastq.gz | RIP-Seq | 131.5 MB | link | |||
| — | XiaoCollab1-5079_IP.R1.fastq.gz | RIP-Seq | 227.3 MB | link | |||
| — | XiaoCollab2-5352_IP.R1.fastq.gz | RIP-Seq | 199.7 MB | link |