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GSE167466

GSE GEO
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Crosstalk between CRISPR-Cas9 and the human transcriptome

Organism: Homo sapiens
Platform: GPL20301
Samples: 12
Experiment Types:
Expression profiling by high throughput sequencing
Submitted: Feb 24 2021
Last Updated: Mar 30 2022
Status: Public on Jan 24 2022
Contact: Gene,,Yeo (UCSD)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA704689 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP307994

Summary

CRISPR-Cas9 expression independent of its cognate synthetic guide RNA (gRNA) causes widespread genomic DNA damage in human cells. To investigate whether Cas9 can interact with endogenous human RNA transcripts independent of its guide, we perform eCLIP (enhanced CLIP) of Cas9 in human cells and find that Cas9 reproducibly interacts with hundreds of endogenous human RNA transcripts. This association can be partially explained by a model built on gRNA secondary structure and sequence. Critically, transcriptome-wide Cas9 binding sites do not appear to correlate with published genome-wide Cas9 DNA binding or cut-site loci under gRNA co-expression. However, even under gRNA co-expression low-affinity Cas9-human RNA interactions (which we term CRISPR crosstalk) do correlate with published elevated transcriptome-wide RNA editing. Our findings do not support the hypothesis that human RNAs can broadly guide Cas9 to bind and cleave human genomic DNA, but they illustrate a clear cellular RNA impact likely inherent to CRISPR-Cas systems.

Overall Design

Crosslinking and immunoprecipitation of dSpCas9 with bound RNA and sequencing from 2 bioreplicates with V5 and FLAG antibodies, with 2 controls (size-matched input; empty vector IP).

Analysis (18 steps)

View Data Processing
Processing steps for GSE167466
  1. Sequenced reads were reformatted to include randomers in read headers with umi_tools (1.0.0).
  2. Args: --random-seed 1 --bc-pattern NNNNNNNNNN
  3. Reads were then trimmed with cutadapt (1.14).
  4. Args: --match-read-wildcards -O 1 --times 1 -e 0.1 --quality-cutoff 6 -m 18 -a InvRNA*.fasta (fasta sequences can be found at: https://github.com/YeoLab/eclip/tree/master/example/inputs/)
  5. Reads were then trimmed once more with cutadapt (1.14) to remove double-ligation events.
  6. Args: --match-read-wildcards -O 5 --times 1 -e 0.1 --quality-cutoff 6 -m 18 -a InvRNA*.fasta (fasta sequences can be found at: https://github.com/YeoLab/eclip/tree/master/example/inputs/)
  7. Trimmed reads were then mapped with STAR (2.4.0i) against a human-specific repeat element database (RepBase 18.05).
  8. Args: --runThreadN 16 \ --genomeDir human_repbase \ --readFilesIn path/to/read1 \ --outFileNamePrefix out_prefix \ --outReadsUnmapped Fastx \ --outSAMtype BAM Unsorted \ --outSAMattributes All \ --outSAMunmapped Within \ --outSAMattrRGline ID:foo \ --outFilterType BySJout \ --outFilterMultimapNmax 30 \ --outFilterMultimapScoreRange 1 \ --outFilterScoreMin 10 \ --alignEndsType EndToEnd
Showing first 8 steps.

Supplementary Files (5)

GSE167466_1P_vs_1N.vs.2P_vs_2N.bed.gz Download
GSE167466_1P_vs_8P.vs.2P_vs_9P.bed.gz Download
GSE167466_4P_IP_vs_11P_input_IDR_6P_IP_vs_12P_input.bed.gz Download
GSE167466_4P_IP_vs_4N_input_IDR_6P_IP_vs_6N_input.bed.gz Download
GSE167466_RAW.tar Download
GEO Samples (12)

Dataset Citations (1)

Crosstalk between CRISPR-Cas9 and the human transcriptome.
PMID 35236841 · 2022 · Nature communications
Aaron A Smargon, Assael A Madrigal, Brian A Yee, Kevin D Dong, Jasmine R Mueller, Gene W Yeo

SRA Experiments (12) and Runs (12)

Total: 7709 MB
SRX10165382 SRP307994 RIP-Seq SINGLE
GSM5105583: V5-dSpCas9 rep 1 size-matched input; Homo sapiens; RIP-Seq
Sample: SRS8316055
BioProject: PRJNA704689
BioSample: SAMN18052998
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: N/A
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRiL19
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779885 23882121 1815041196 643.23 V5_CAS9_1N_S1_L001_R1_001.fastq.gz, SRR13779885, SRR13779885.lite SRA
SRX10165383 SRP307994 RIP-Seq SINGLE
GSM5105584: V5-dSpCas9 rep 1 V5 IP; Homo sapiens; RIP-Seq
Sample: SRS8316056
BioProject: PRJNA704689
BioSample: SAMN18052997
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: ThermoFisher Scientific
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA1
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779886 25243266 1918488216 686.37 V5_CAS9_1P_S2_L001_R1_001.fastq.gz, SRR13779886, SRR13779886.lite SRA
SRX10165384 SRP307994 RIP-Seq SINGLE
GSM5105585: V5-dSpCas9 rep 2 size-matched input; Homo sapiens; RIP-Seq
Sample: SRS8316057
BioProject: PRJNA704689
BioSample: SAMN18053020
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: N/A
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRiL19
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779887 16028948 1218200048 419.85 Assa_2N_S60_L005_R1_001.fastq.gz, SRR13779887, SRR13779887.lite SRA
SRX10165386 SRP307994 RIP-Seq SINGLE
GSM5105586: V5-dSpCas9 rep 2 V5 IP; Homo sapiens; RIP-Seq
Sample: SRS8316060
BioProject: PRJNA704689
BioSample: SAMN18053019
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: ThermoFisher Scientific
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA1
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779888 22043341 1675293916 591.44 Assa_2P_S61_L005_R1_001.fastq.gz, SRR13779888, SRR13779888.lite SRA
SRX10165387 SRP307994 RIP-Seq SINGLE
GSM5105587: Empty vector V5 IP rep 1 input; Homo sapiens; RIP-Seq
Sample: SRS8316059
BioProject: PRJNA704689
BioSample: SAMN18053018
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: ThermoFisher Scientific
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA3
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779889 35142422 2670824072 955.25 V5_pCDNA_8P_S9_L001_R1_001.fastq.gz, SRR13779889, SRR13779889.lite SRA
SRX10165388 SRP307994 RIP-Seq SINGLE
GSM5105588: Empty vector V5 IP rep 2 input; Homo sapiens; RIP-Seq
Sample: SRS8316061
BioProject: PRJNA704689
BioSample: SAMN18053017
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: ThermoFisher Scientific
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA3
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779890 23480278 1784501128 644.08 V5_pCDNA_9P_S10_L001_R1_001.fastq.gz, SRR13779890, SRR13779890.lite SRA
SRX10165389 SRP307994 RIP-Seq SINGLE
GSM5105589: 3xFLAG-dSpCas9 rep 1 size-matched input; Homo sapiens; RIP-Seq
Sample: SRS8316062
BioProject: PRJNA704689
BioSample: SAMN18053016
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: N/A
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRiL19
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779891 22111242 1680454392 602.85 FLAG_CAS9_4N_S5_L001_R1_001.fastq.gz, SRR13779891, SRR13779891.lite SRA
SRX10165390 SRP307994 RIP-Seq SINGLE
GSM5105590: 3xFLAG-dSpCas9 rep 1 FLAG IP; Homo sapiens; RIP-Seq
Sample: SRS8316063
BioProject: PRJNA704689
BioSample: SAMN18053015
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: Sigma-Aldrich
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA2
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779892 24534276 1864604976 681.25 FLAG_CAS9_4P_S6_L001_R1_001.fastq.gz, SRR13779892, SRR13779892.lite SRA
SRX10165391 SRP307994 RIP-Seq SINGLE
GSM5105591: 3xFLAG-dSpCas9 rep 2 size-matched input; Homo sapiens; RIP-Seq
Sample: SRS8316064
BioProject: PRJNA704689
BioSample: SAMN18053014
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: N/A
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRiL19
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779893 21799767 1656782292 592.44 FLAG_CAS9_6N_S7_L001_R1_001.fastq.gz, SRR13779893, SRR13779893.lite SRA
SRX10165392 SRP307994 RIP-Seq SINGLE
GSM5105592: 3xFLAG-dSpCas9 rep 2 FLAG IP; Homo sapiens; RIP-Seq
Sample: SRS8316065
BioProject: PRJNA704689
BioSample: SAMN18053013
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: Sigma-Aldrich
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA2
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779894 22589919 1716833844 617.6 FLAG_CAS9_6P_S8_L001_R1_001.fastq.gz, SRR13779894, SRR13779894.lite SRA
SRX10165393 SRP307994 RIP-Seq SINGLE
GSM5105593: Empty vector FLAG IP rep 1 input; Homo sapiens; RIP-Seq
Sample: SRS8316066
BioProject: PRJNA704689
BioSample: SAMN18053012
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: Sigma-Aldrich
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA4
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779895 22066895 1677084020 610.42 FLAG_pCDNA_11P_S11_L001_R1_001.fastq.gz, SRR13779895, SRR13779895.lite SRA
SRX10165394 SRP307994 RIP-Seq SINGLE
GSM5105594: Empty vector FLAG IP rep 2 input; Homo sapiens; RIP-Seq
Sample: SRS8316067
BioProject: PRJNA704689
BioSample: SAMN18053011
Platform: ILLUMINA
Instrument: Illumina HiSeq 4000
Organism: Homo sapiens
Sample attributes
source_name: HEK293T
antibody manufacturer: Sigma-Aldrich
cell manufacturer: Takara Bio
cell line: Lenti-X 293T (HEK 293T)
adapter: InvRNA4
Original files (1)
HEK293T
Runs (1)
Run Spots Bases Size (MB) Files Link
SRR13779896 24069912 1829313312 664.17 FLAG_pCDNA_12P_S12_L001_R1_001.fastq.gz, SRR13779896, SRR13779896.lite SRA

Linked Publications (1)

Potentially Related Publications (1)

This accession was text-mined from the PMC full text of these publications. It may be referenced for comparison or reused from another study rather than generated for them.

Data Files (24)

Accession File Name Stored Type Output Type Mapping Assembly Size Download
— Assa_2N_S60_L005_R1_001.fastq.gz RIP-Seq 419.8 MB link
— Assa_2P_S61_L005_R1_001.fastq.gz RIP-Seq 591.4 MB link
— FLAG_CAS9_4N_S5_L001_R1_001.fastq.gz RIP-Seq 602.8 MB link
— FLAG_CAS9_4P_S6_L001_R1_001.fastq.gz RIP-Seq 681.2 MB link
— FLAG_CAS9_6N_S7_L001_R1_001.fastq.gz RIP-Seq 592.4 MB link
— FLAG_CAS9_6P_S8_L001_R1_001.fastq.gz RIP-Seq 617.6 MB link
— FLAG_pCDNA_11P_S11_L001_R1_001.fastq.gz RIP-Seq 610.4 MB link
— FLAG_pCDNA_12P_S12_L001_R1_001.fastq.gz RIP-Seq 664.2 MB link
— SRR13779885_GSM5105583 RIP-Seq 643.0 MB link
— SRR13779886_GSM5105584 RIP-Seq 686.0 MB link
— SRR13779887_GSM5105585 RIP-Seq 419.0 MB link
— SRR13779888_GSM5105586 RIP-Seq 591.0 MB link
— SRR13779889_GSM5105587 RIP-Seq 955.0 MB link
— SRR13779890_GSM5105588 RIP-Seq 644.0 MB link
— SRR13779891_GSM5105589 RIP-Seq 602.0 MB link
— SRR13779892_GSM5105590 RIP-Seq 681.0 MB link
— SRR13779893_GSM5105591 RIP-Seq 592.0 MB link
— SRR13779894_GSM5105592 RIP-Seq 617.0 MB link
— SRR13779895_GSM5105593 RIP-Seq 610.0 MB link
— SRR13779896_GSM5105594 RIP-Seq 664.0 MB link
— V5_CAS9_1N_S1_L001_R1_001.fastq.gz RIP-Seq 643.2 MB link
— V5_CAS9_1P_S2_L001_R1_001.fastq.gz RIP-Seq 686.4 MB link
— V5_pCDNA_8P_S9_L001_R1_001.fastq.gz RIP-Seq 955.2 MB link
— V5_pCDNA_9P_S10_L001_R1_001.fastq.gz RIP-Seq 644.1 MB link