run_metadata: 34183

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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
34183	SRR31399562	SRX26768858	SRS23256161	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 8–9 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.				eif6 2	GSM8641202		source name:whole larvae\|tissue:whole larvae\|cell line:5 dpf\|genotype:eif6 KO\|geo loc name:missing\|collection date:missing	eif6 2	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’ adapter sequences were then trimmed from the remaining high quality reads. Finally reads were removed if they: 1 lacked a 3’ adapter sequence 2 were 5’ 3’ adapter ligation products 3 were 5’ 5’ 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		tissue:whole larvae\|cell line:5 dpf\|genotype:eif6 KO	GSM8641202	GSM8641202: eif6 2; Danio rerio; RNA Seq	GSM8641202 r1	GSM8641202	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		RNA-Seq	TRANSCRIPTOMIC	cDNA	PAIRED	BGISEQ	BGISEQ-500		SRP546207			eif6_2_1.fq.gz eif6_2_2.fq.gz	fastq fastq	6968721400.0	34843607.0	GSM8641202 r1	0:100 1:100	A:1798630009;C:1650901437;G:1708195694;T:1810994260;N:0	100	100			1798630009	1650901437	1708195694	1810994260	0	SRX26768858	SRS23256161	SRA2017777	Cleveland Clinic	Cleveland Clinic												B	B	biological fallback assumption	bgi	bgi	unknown	small_rna	unknown	bulk	unknown	unknown		United States	2024-11-19	Larval	Larval	Whole Organism	All anatomical structures