GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE112463 Query DataSets for GSE112463
Status Public on Feb 04, 2019
Title Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen
Organisms Escherichia coli; Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, and 3) predicted affected biological pathways. We further demonstrated the implementation of intermediate time points for the identification of early and late response genes. This study illustrated the power of a genome-wide CRISPR-Cas9 screen to systematically identify novel genes involved in APAP-induced hepatotoxicity and to provide potential targets to develop novel therapeutic modalities.
Overall design Single-read DNA amplicon sequencing of a CRISPR/Cas9 genome-wide knockout screen of acetaminophen-induced hepatotoxicity in the HuH7 human hepatocarcinoma cell line. sgRNA library transfer plasmid isolated from E. coli was sequenced alongside the screen to assess library representation. For each sample there are 4 technical replicates.
Contributor(s) Shortt K, Heruth DP, Zhang N, Wu W, Singh S, Li D, Zhang LQ, Wyckoff G, Qi LS, Ye SQ
Citation(s) 30718897
Submission date Mar 28, 2018
Last update date Feb 06, 2019
Contact name Shui Q Ye
Organization name University of Missouri Kansas City School of Medicine
Department Departmetn of Biomedical and Health Informatics
Street address 2411 Holmes Street
City Kansas City
State/province MO
ZIP/Postal code 64108
Country USA
Platforms (2)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL20045 Illumina HiSeq 1500 (Escherichia coli)
Samples (12)
GSM3070501 Plasmid_rep1
GSM3070502 Plasmid_rep2
GSM3070503 T0_rep1
BioProject PRJNA447595
SRA SRP136733

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE112463_raw_read_counts.txt.gz 2.7 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap