run_metadata: 71679

This data as json

rowid	run.accession	experiment.accession	sample.accession	study.accession	bioproject	study.title	study.alias	study.type	study.abstract	study.attributes	study.PMIDs	sample.description	sample.title	sample.alias	sample.centername	sample.attributes	GEOsample.title	GEOsample.dataprocessing	GEOsample.source	GEOsample.treatmentprotocol	GEOsample.extractprotocol	GEOsample.growthprotocol	GEOsample.characteristics	GEOsample.accession	experiment.title	experiment.alias	experiment.library_name	experiment.design_description	experiment.library_construction_protocol	experiment.attributes	experiment.library_strategy	experiment.library_source	experiment.library_selection	experiment.library_layout	experiment.platform	experiment.instrument_model	experiment.spot_descriptor	experiment.study_ref	run.title	run.attributes	run.filename	run.semantic_name	run.total_bases	run.total_spots	run.alias	run.read_lengths	run.base_counts	run.r1_length	run.r2_length	run.r3_length	run.r4_length	run.Acount	run.Ccount	run.Gcount	run.Tcount	run.Ncount	run.experiment	run.pool_member	submission.accession	submission.srasource	submission.bioprojectsource	seqdetective.n_mates	seqdetective.mapping_rate.mate1	seqdetective.mapping_rate.mate2	seqdetective.nofeature_rate.mate1	seqdetective.nofeature_rate.mate2	seqdetective.sparsity.mate1	seqdetective.sparsity.mate2	seqdetective.pos_strand_rate.mate1	seqdetective.pos_strand_rate.mate2	seqdetective.readlen.mate1	seqdetective.readlen.mate2	seqdetective.judgement.mate1	seqdetective.judgement.mate2	seqdetective.judgement.reason	platform_family	instrument_generation	read_bias	selection_class	prep_kit	sc_or_bulk	tech_class	technology	tech_variant	submission.bioprojectsource.country	earliest_date	devstage_curation	devstage_curation_coarse	tissue_curation	tissue_curation_coarse
71679	SRR21930622	SRX17915128	SRS15430830	SRP403013	PRJNA891244	Hepatic processing of Z variant a 1 antitrypsin alters ERAD capacity to regulate cholesterol biosynthesis in a zebrafish model	GSE215899	Transcriptome Analysis	Homozygosity for the Z allele of a1 antitrypsin ZAAT predisposes affected individuals to developing liver disease as the serpin misfolds and forms insoluble polymers that accumulate in the endoplasmic reticulum ER of hepatocytes resulting in gain of function hepatotoxicity. This prevents secretion of ZAAT leading to serum insufficiency. A zebrafish model expressing human ZAAT in the liver shows no signs of hepatic accumulation despite displaying serum insufficiency suggesting defect in ZAAT secretion occurs independently of its tendency to accumulate in hepatocytes. In this study global transcriptomic approach was used to identify pathways activated and operating in the ZAAT expressing zebrafish liver. The analysis provided strong evidence of suppressed Srebp2 mediated cholesterol biosynthesis. qPCR confirms this observation in the human liver cell line stably expressing ZAAT. We proposed that the engagement of misfolded ZAAT by the ER associated degradation ERAD system inhibits the turnover of Srebp2 repressing elements therefore hindering the activation of Srebp2. Overall design: Comparative gene expression profiling analysis of RNA seq data for transgenic zebrafish liver expressing wildtype or Z mutant human antitrypsin and their non transgenic siblings.		pubmed:36768797		Aplus3	GSM6645215		source name:Liver\|tissue:Liver\|strain:Tglfabp:eGFP T2A AAT\|developmental stage:2 mpf	Aplus3	The fastq files were aligned to a custom genome GRCz11 that includes the AAT transgene ensembl release 92 curated to remove contigs unknown and alternate chromsomes using RNAsik pipeline version 1.4.7. A matching custom GTF annotation file was generated as well The RNAsik pipeline was run with the following parameters: ‘ align star paired all’ and used the combined fasta file and gtf file as input for the ‘ fastaRef’ and ‘ gtfFile’ parameters. The RNAsik pipeline uses STAR to align fastq files to the reference genome and then uses featureCounts to assign aligned reads to annotated genes. The raw counts were filtered to keep only genes with 100 in at least 3 samples. The data was then normalised to RPKM. Using multiple t tests Z+ was tested against the 3 other groups as well as p > 0.05 between the A and Z groups to ensure no difference in gene expression in non transgenic animals for it to be defined as a differential gene. A threshold on type I error from multiple tests was also applied so that the sum of the three p values do not exceed 0.01. Assembly: Ensembl GRCz11 modified to include the AAT transgene Supplementary files format and content: comma separated file containing raw counts for each sample	Liver		Total RNA was isolated from fish liver using Trizol lysis reagent Sigma Aldrich followed by isopropanol precipitation and the RNA pellet washed with 70% v/v ethanol. PolyA RNA seq libraries prepared using Ilumina TruSeq Stranded mRNA Sample prep kit following manufacturer's protocols.	Zebrafish were maintained at 28°C on a 14 h light/10 h dark cycle	tissue:Liver\|strain:Tglfabp:eGFP T2A AAT\|developmental stage:2 mpf	GSM6645215	GSM6645215: Aplus3; Danio rerio; RNA Seq	GSM6645215 r1	GSM6645215	1	Total RNA was isolated from fish liver using Trizol lysis reagent Sigma Aldrich followed by isopropanol precipitation and the RNA pellet washed with 70% v/v ethanol. PolyA RNA seq libraries prepared using Ilumina TruSeq Stranded mRNA Sample prep kit following manufacturer's protocols.		RNA-Seq	TRANSCRIPTOMIC	cDNA	PAIRED	ILLUMINA	NextSeq 550		SRP403013			Aplus3_S15_R1_001.fastq.gz Aplus3_S15_R2_001.fastq.gz	fastq fastq	6881303008.0	45881629.0	GSM6645215 r1	0:74.67 1:75.31	A:1705776092;C:1687176683;G:1744678234;T:1714771420;N:28900579	74	75			1705776092	1687176683	1744678234	1714771420	28900579	SRX17915128	SRS15430830	SRA1521803	Monash Bioinformatics Platform, Monash Bioinformatics Platform	Monash Bioinformatics Platform, Monash Bioinformatics Platform	2	0.97636	0.97803	0.04693	0.04579	0.82106	0.82313	0.57573	0.57226	74	76	B	B	biological fallback assumption	illumina	nextseq	unknown	poly_a	trueseq	bulk	unknown	unknown		Australia	2022-10-17	Juvenile	Juvenile	Liver	Liver and Biliary System