{"database": "metadata", "table": "run_metadata", "rows": [[34185, "SRR31399564", "SRX26768856", "SRS23256158", "SRP546207", "PRJNA1188114", "Reduced  EIF6 dosage attenuates TP53 activation in models  of Shwachman Diamond syndrome", "GSE282310", "Transcriptome Analysis", "Shwachman Diamond syndrome SDS is characterized by neutropenia  exocrine pancreatic insufficiency  and bony abnormalities with an increased risk of myeloid neoplasia.  Almost all cases of SDS result from biallelic mutations in SBDS. SBDS interacts with EFL1 to displace EIF6 from the 60S ribosomal subunit. Released EIF6 permits the assembly of ribosomal large and small subunits in the cytoplasm. Decreased EIF6 levels due to haploinsufficiency or missense mutations which lead to decreased protein expression may provide a somatic genetic rescue and anti leukemic effects.  We observed accumulation of EIF6 protein in sbds knockout KO zebrafish models  confirmed in patient derived tissues  and correlated with changes in ribosome proteins and TP53 pathways. The mechanism of action for this adaptive response is unknown. To address this  we generated an eif6 zebrafish KO line which do not survive past 10 dpf We also created two mutants with low Eif6 expression  5 25% of the wildtype levels  that can survive until maturity. We bred them with sbds null strains and analyzed their phenotype and biochemical properties. Low Eif6 levels reduced Tp53 pathway activation but did not rescue neutropenia in Sbds deficient zebrafish. Further studies elucidating the interplay between SBDS  EIF6  TP53  and cellular stress responses offer promising insights into SDS pathogenesis  somatic genetic rescue  and therapeutic strategies. Overall design: RNA was extracted from pools of 8\u20139 individually genotyped larvae at 10 dpf using TRIzol. Three pools of eif6 /  or wildtype from the same clutch were compared. RNA quality was determined by Bioanalyzer Agilent  and eif6 mRNA expression was measured by RT qPCR. RNA Seq library preparation and sequencing and mapping of 3 pools of eif6 /  and 3 pools of eif6+/+ were performed by the Beijing Genome Institute 4. Based on the FPKM values 39  we used EBSeq R package for differentially expressed gene detection between eif6 /  and eif6+/+ fold change > 2  and P < 0.05.", null, null, null, "wt3", "GSM8641200", null, "source name:whole larvae|tissue:whole larvae|cell line:5 dpf|genotype:eif6 wildtype|geo loc name:missing|collection date:missing", "wt3", "Reads were processed to remove low quality reads and trim artificial adapter sequences following BGI protocols. Briefly  reads were marked and removed for low quality if they had [either more than 4 bases whose quality score is lower than 10 or more than 6 bases whose quality score was lower than 13]. 3\u2019 adapter sequences were then trimmed from the remaining high quality reads. Finally  reads were removed if they: 1 lacked a 3\u2019 adapter sequence  2 were 5\u2019 3\u2019 adapter ligation products  3 were 5\u2019 5\u2019 adapter ligation products  4 were shorter than 18 nt  or 5 contained only As homopolymers. High quality reads were aligned to the reference C. elegans genome version WS220 using Bowtie2 with the following parameters:  f  N 0  M 10. Reads that aligned with zero mismatches to one genomic locus were annotated to mature miRNA coordinates from miRBase v19. Assembly: GCF 000002035.6 GRCz11 Supplementary files format and content: csv file. FPKM values and p and q values", "whole larvae", "5 dpf", "RNA was harvested using TRIzol  following the manufacturer's instructions. Total RNA was submitted to BGI for small RNA seq library construction and deep sequencing. BGISeq 500 sequencing platform", null, "tissue:whole larvae|cell line:5 dpf|genotype:eif6 wildtype", "GSM8641200", "GSM8641200: wt3; Danio rerio; RNA Seq", "GSM8641200 r1", "GSM8641200", "1", "RNA was harvested using TRIzol  following the manufacturer's instructions. Total RNA was submitted to BGI for small RNA seq library construction and deep sequencing. BGISeq 500 sequencing platform", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "BGISEQ", "BGISEQ-500", null, "SRP546207", null, null, "wt3_1.fq.gz wt3_2.fq.gz", "fastq fastq", 6990771600.0, 34953858.0, "GSM8641200 r1", "0:100 1:100", "A:1823561732;C:1639273273;G:1691098287;T:1836838308;N:0", 100, 100, null, null, 1823561732, 1639273273, 1691098287, 1836838308, 0, "SRX26768856", "SRS23256158", "SRA2017777", "Cleveland Clinic", "Cleveland Clinic", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "bgi", "bgi", "unknown", "small_rna", "unknown", "bulk", "unknown", "unknown", null, "United States", "2024-11-19", "Larval", "Larval", "Whole Organism", "All anatomical structures"]], "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": ["34185"], "units": {}, "query_ms": 10.577549999652547}