run_metadata: 55211

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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
55211	SRR10153633	SRX6879048	SRS5414796	SRP222804	PRJNA573071	Bulk transcriptomic analysis of two models of zebrafish beta catenin driven HCC	GSE137787	Transcriptome Analysis	Up to 41% of hepatocellular carcinomas HCCs result from activating mutations in the CTNNB1 gene encoding ß catenin. ß catenin has dual cellular functions as a component of the Wnt signaling pathway and adherens junctions. HCC associated CTNNB1 mutations stabilize the ß catenin protein leading to nuclear and/or cytoplasmic localization of ß catenin and downstream activation of Wnt target genes. In patient HCC samples ß catenin nuclear and cytoplasmic localization are typically patchy even among HCC with highly active CTNNB1 mutations. The functional and clinical relevance of this heterogeneity in ß catenin activation are not well understood. To define mechanisms of ß catenin driven HCC initiation we generated a Cre lox system that enabled switching on activated ß catenin in 1 a small number of hepatocytes in early development; or 2 the majority of hepatocytes in later development or maturity. We discovered that switching on activated ß catenin in a subset of larval hepatocytes was sufficient to drive HCC initiation. To determine the role of Wnt/ß catenin signaling heterogeneity later in hepatocarcinogenesis we performed RNA seq analysis of zebrafish ß catenin driven HCC. Ingenuity Pathway Analysis of differentially expressed genes in the Cre lox HCC model revealed that “Cancer” and “Liver Tumor” categories were significantly altered indicating transcriptional similarities with human HCC and other vertebrate HCC models. At the single cell level 2.9% to 15.2% of hepatocytes from zebrafish ß catenin driven HCC expressed two or more of the Wnt target genes axin2 mtor glula myca and wif1 indicating focal activation of Wnt signaling in established tumors. Thus heterogeneous ß catenin activation drives HCC initiation and persists throughout hepatocarcinogenesis. Overall design: Examination of HCC and nonHCC liver samples from two different models of zebrafish compared to wildtype/nonHCC siblings.	parent bioproject:PRJNA573068	pubmed:31575545		624	GSM4087868		tissue:Liver\|transgenic line:Tgfabp10a CreERT2;fabp10a flox beta catenin\|age:11 mpf at larval stg:10micromolar 4 hydroxytamoxifen from 3 dpf to 6 dpf	624	The Zebrafish GRCz11 FASTA and GTF files were downloaded from Ensembl release 94. The reference database was created using STAR version 2.6.1b with splice junctions optimized for 125 base pair reads. Reads were trimmed of adapters and aligned to the reference database using STAR in two pass mode to output a BAM file sorted by coordinates. Mapped reads were assigned to annotated genes in the GTF file using featureCounts version 1.6.3. Differentially expressed genes were identified using a 5% false discovery rate with DESeq2 version 1.22.2. Genome build: GRCz11 Supplementary files format and content: Raw gene expression quantification with featureCounts v1.6.3 was collated into a tab delimited matrix where each column denotes a sample and each row corresponds to a gene.	Liver	Larvae were treated with either 0.1% ethanol or 10micromolar 4 hydroxytamoxifen from 3 dpf to 6 dpf	Zebrafish were euthanized by rapid chilling and their livers were dissected. Half of each liver was submitted for histologic evaluation to confirm the diagnosis HCC or no HCC. The other half of each dissected liver was flash frozen on dry ice and stored in 80C prior to RNA extraction. RNA was isolated using TriReagent Cat# R2050 1 50 Zymo Research and Direct Zol RNA Mini prep kit Cat# R2050 Zymo Research including DNase treatment following manufacturer’s protocols. Samples were eluted in RNase /DNase free water. Sample quality control library preparation sequencing and alignments were performed by the Huntsman Cancer Institute HCI High Throughput Genomics and Bioinformatic Analysis Shared Resource. Paired read 150 base pair sequencing was performed using Illumina’s NovaSeq instrument. Three or four pooled libraries were run on each lane of the flow cell. Illumina TruSeq Stranded mRNA Library Prep RIN 8 10	Fish were raised following IACUC approved protocols in insititutional zebrafish facility.	transgenic line:Tgfabp10a CreERT2;fabp10a flox beta catenin\|age:11 mpf at larval stg:10micromolar 4 hydroxytamoxifen from 3 dpf to 6 dpf	GSM4087868	GSM4087868: 624; Danio rerio; RNA Seq	GSM4087868		1	Zebrafish were euthanized by rapid chilling and their livers were dissected. Half of each liver was submitted for histologic evaluation to confirm the diagnosis HCC or no HCC. The other half of each dissected liver was flash frozen on dry ice and stored in 80C prior to RNA extraction. RNA was isolated using TriReagent Cat# R2050 1 50 Zymo Research and Direct Zol RNA Mini prep kit Cat# R2050 Zymo Research including DNase treatment following manufacturer's protocols. Samples were eluted in RNase /DNase free water. Sample quality control library preparation sequencing and alignments were performed by the Huntsman Cancer Institute HCI High Throughput Genomics and Bioinformatic Analysis Shared Resource. Paired read 150 base pair sequencing was performed using Illumina's NovaSeq instrument. Three or four pooled libraries were run on each lane of the flow cell. Illumina TruSeq Stranded mRNA Library Prep RIN 8 10	GEO Accession:GSM4087868	RNA-Seq	TRANSCRIPTOMIC	cDNA	PAIRED	ILLUMINA	Illumina NovaSeq 6000		SRP222804			16048X8_190607_A00421_0071_BHL22MDSXX_S19_L004_R1_001.fastq.gz 16048X8_190607_A00421_0071_BHL22MDSXX_S19_L004_R2_001.fastq.gz	fastq fastq	9818272170.0	32510835.0	GSM4087868 r1	0:151 1:151	A:2609919214;C:2318388621;G:2406490919;T:2483290917;N:182499	151	151			2609919214	2318388621	2406490919	2483290917	182499	SRX6879048	SRS5414796	SRA965568	GEO	Pathology, University of California, San Francisco	2	0.95073	0.95151	0.04785	0.0469	0.80919	0.81055	0.54958	0.55772	151	151	B	B	biological fallback assumption	illumina	novaseq_era	unknown	cdna_unspecified	trueseq	bulk	bulk	bulk		United States	2019-09-20	Multi-stage	Multi-stage	Liver	Liver and Biliary System