{"database": "metadata", "table": "run_metadata", "rows": [[71674, "SRR21930617", "SRX17915133", "SRS15430835", "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.", null, "pubmed:36768797", null, "Aminus2", "GSM6645220", null, "source name:Liver|tissue:Liver|strain:Non transgenic sibling|developmental stage:2 mpf", "Aminus2", "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: \u2018 align star  paired  all\u2019 and used the combined fasta file and gtf file as input for the \u2018 fastaRef\u2019 and \u2018 gtfFile\u2019 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", null, "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\u00b0C on a 14 h light/10 h dark cycle", "tissue:Liver|strain:Non transgenic sibling|developmental stage:2 mpf", "GSM6645220", "GSM6645220: Aminus2; Danio rerio; RNA Seq", "GSM6645220 r1", "GSM6645220", "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.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "NextSeq 550", null, "SRP403013", null, null, "Aminus2_S20_R1_001.fastq.gz Aminus2_S20_R2_001.fastq.gz", "fastq fastq", 6328688976.0, 42049798.0, "GSM6645220 r1", "0:75.16 1:75.34", "A:1583871529;C:1558452442;G:1563731549;T:1612985194;N:9648262", 75, 75, null, null, 1583871529, 1558452442, 1563731549, 1612985194, 9648262, "SRX17915133", "SRS15430835", "SRA1521803", "Monash Bioinformatics Platform, Monash Bioinformatics Platform", "Monash Bioinformatics Platform, Monash Bioinformatics Platform", 2, 0.98159, 0.98224, 0.04493, 0.04338, 0.80748, 0.81117, 0.54259, 0.53675, 76, 75, "B", "B", "biological fallback assumption", "illumina", "nextseq", "unknown", "poly_a", "trueseq", "bulk", "unknown", "unknown", null, "Australia", "2022-10-17", "Juvenile", "Juvenile", "Liver", "Liver and Biliary System"]], "columns": ["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"], "primary_keys": ["rowid"], "primary_key_values": ["71674"], "units": {}, "query_ms": 10.553050000453368}