{"database": "metadata", "table": "run_metadata", "rows": [[34361, "SRR31668412", "SRX27031093", "SRS23495058", "SRP550584", "PRJNA1196438", "DNA Damage Response Deficiency Enhances Neuroblastoma Progression and Sensitivity to Combination PARP and ATR Inhibition", "GSE283976", "Transcriptome Analysis", "Next generation sequencing of neuroblastoma NB tumors have revealed frequent somatic and germline genetic alterations in genes encoding proteins involved in DNA damage response DDR pathways. Despite being well studied in many adult cancers  roles for DDR disruption in pediatric solid tumors have not been fully elucidated. To address this  patient relevant loss of function mutations in DDR pathway components including Brca2  Atm  and Palb2 were incorporated into an established zebrafish MYCN transgenic model Tgdbh:EGFP MYCN. These mutations were found to enhance NB formation and metastasis in vivo  and result in upregulation of proliferation  cell cycle checkpoint and DNA damage repair transcriptional signatures  revealing novel molecular vulnerabilities in DDR deficient NB. Zebrafish DDR deficient NB and human NB cells with DDR protein knock down were sensitive to the polyADP ribose polymerase PARP inhibitor olaparib  and this effect was further enhanced by inhibition of the ataxia telangiectasia and rad3 related ATR kinase. Altogether  our data supports a functional role for DDR deficiency in NB in vivo and therapeutic potential for combination PARP + ATR inhibition in NB patients with alterations in DDR genes. Overall design: To capture broad transcriptomic differences associated with HDR/DDR deficiency in primary and transplanted neuroblastoma  we performed RNA sequencing of GFP+ sorted tumor cells from zebrafish MYCN driven neuroblastoma from various engineered genetic backgrounds", null, null, null, "MYCN driven brca2+/ ;tp53 /  primary neuroblastoma  biological sample 3", "GSM8675194", null, "source name:GFP+ sorted neuroblastoma|tissue:GFP+ sorted neuroblastoma|cell type:neuroblastoma|genotype:MYCN;brca2+/ ;tp53 / |geo loc name:missing|collection date:missing", "MYCN driven brca2+/ ;tp53 /  primary neuroblastoma  biological sample 3", "Raw .fastq data was processed using Salmon quantification of transcripts. A \u201cdecoy aware\u201d index was built with the Danio rerio transcriptome and genome using the GRCz11 assembly with a k mers length of 23. Samples were quantified with the following arguments:  r    seqBias    mp  3    validateMappings    rangeFactorizationBins 4. Assembly: GRCz11 Supplementary files format and content: Comma separated values .csv file including raw non normalized counts for all conditions generated by Salmon", "GFP+ sorted neuroblastoma", "All animal monitoring and sample collection were performed in accordance with animal use protocols approved by the Hospital for Sick Children Animal Care Committee #1000054111  #1000064586.", "Dissected neuroblastoma tumors were manually dissociated and processed to single cell suspensions. GFP+ tumor cells were sorted from bulk tissue at the SickKids UHN Flow Cytometry Core Facility on a Sony MA900 VBYR cell sorter  before pelleting and lysis using Qiagen RNeasy Mini Kit  as per manufacturer instructions. Sequence ready polyA enriched libraries were prepared using the NEB Ultra II Directional mRNA prep kit for Illumina NEB  E7760. Sequence ready polyA enriched libraries were prepared using the NEB Ultra II Directional mRNA prep kit for Illumina NEB  E7760.", "Zebrafish were reared and maintained according to standard husbandry procedure at the Zebrafish Genetics and Disease Modeling Core Facility at the Hospital for Sick Children.", "tissue:GFP+ sorted neuroblastoma|cell type:neuroblastoma|genotype:MYCN;brca2+/ ;tp53 / ", "GSM8675194", "GSM8675194: MYCN driven brca2+/ ;tp53 /  primary neuroblastoma  biological sample 3; Danio rerio; RNA Seq", "GSM8675194 r1", "GSM8675194", "1", "Dissected neuroblastoma tumors were manually dissociated and processed to single cell suspensions. GFP+ tumor cells were sorted from bulk tissue at the SickKids UHN Flow Cytometry Core Facility on a Sony MA900 VBYR cell sorter  before pelleting and lysis using Qiagen RNeasy Mini Kit  as per manufacturer instructions. Sequence ready polyA enriched libraries were prepared using the NEB Ultra II Directional mRNA prep kit for Illumina NEB  E7760. Sequence ready polyA enriched libraries were prepared using the NEB Ultra II Directional mRNA prep kit for Illumina NEB  E7760.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "Illumina NovaSeq X", null, "SRP550584", null, null, "brca2_3_R1.fastq.gz brca2_3_R2.fastq.gz", "fastq fastq", 24462829594.0, 81002747.0, "GSM8675194 r1", "0:151 1:151", "A:6540455142;C:5666171087;G:5856369054;T:6399621980;N:212331", 151, 151, null, null, 6540455142, 5666171087, 5856369054, 6399621980, 212331, "SRX27031093", "SRS23495058", "SRA2031529", "Hayes Lab, DSCB, Sickkids Research", "Hayes Lab, DSCB, Sickkids Research", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "illumina", "novaseq_era", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Canada", "2024-12-10", "Undetermined", "Undetermined", "Cancer or Tumor", "Cancer or Tumor"]], "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": ["34361"], "units": {}, "query_ms": 11.506679002195597}