1002 results for "1993+article+mouse+line+professor"

in 14.14 milliseconds.

• MSI2 knockdown and inhibition in mantle cell lymphoma cell lines RNAseq data

  Fastq transcriptomic sequencing files from Z138 mantle cell lymphoma (MCL) cell line upon MSI2 knockdown (KD) with two different shRNAs and after MSI2 inhibition with Ro 08-2750 small molecule. Dataset includes 4 samples of Z138 MSI2-KD, 4 of Z138 control, 3 of Z138 treated with Ro 08-2750 and 3 of Z138 treated with DMSO.

  Dataset EGAD00001009420

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX049_SA928_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005177

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX004_SA605X3XB01966_004

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005162

• RNAseq of primary mesothelioma cell lines

  Mesothelioma is an aggressive cancer associated with previous exposure to asbestos and dismal prognosis. Since a pemetrexed/cisplatin combination was introduced for treatment of mesothelioma, no new first- or second-line therapies have been discovered. Thus, to better understand what drives mesothelioma carcinogenesis and to identify potential targets for therapy, in this project we aim at performing RNAseq analysis of a panel of mesothelioma cells lines.

  Dataset EGAD00001010924

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX021_SA854_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005141

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX021_SA854_004

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005144

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX023_SA604X9XB02413_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 24 samples; filetype=fastq

  Dataset EGAD00001005146

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX019_SA604X7XB02089_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 36 samples; filetype=fastq

  Dataset EGAD00001005151

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX006_PBC04106_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005164

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX_015_SA604X6XB01979_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005155

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX004_SA605X3XB01966_003

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005161

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX051_PBC04633_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005169

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX056_VOA11924F_37C

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005171

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX057_SA535X5XB02887_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005174

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX054_SA604X9XB02417_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005172

• Cancer RNA-seq consisting of FASTQ paired-end reads from melanoma and lung cancer sample

  Cancer RNA-seq consisting of FASTQ paired-end reads from 6 individuals (4 melanoma, 1 lung cancer). RNASEQ was performed on illumina, Truseq capture kit, 40M-80M clusters. 2 Melanoma datasets contain reads from 1 tumor region and from a tumor derived cell line 2 Melanoma, 1 Colon and 1 lung datasets contain each reads from a single region.

  Dataset EGAD00001007951

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX049_SA928_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005176

• RNAseq of primary mesothelioma cell lines

  Mesothelioma is an aggressive cancer associated with previous exposure to asbestos and dismal prognosis. Since a pemetrexed/cisplatin combination was introduced for treatment of mesothelioma, no new first- or second-line therapies have been discovered. Thus, to better understand what drives mesothelioma carcinogenesis and to identify potential targets for therapy, in this project we aim at performing RNAseq analysis of a panel of mesothelioma cells lines.

  Dataset EGAD00001009642

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX020_SA604X8XB02164_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005149

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX026_VOA11083SD_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005158

• Follicular lymphoma at diagnosis, treated in first line with immunochemotherapy

  We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score) in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).

  Dataset EGAD00001009647

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX021_SA854_003

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005143

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX023_SA604X9XB02413_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005145

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX054_SA604X9XB02417_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005173

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX067_VOA12024_003

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005180

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX019_SA604X7XB02089_004

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 24 samples; filetype=fastq

  Dataset EGAD00001005153

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX003_SA605X3XB01966_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005160

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX018_VOA11019SA_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 24 samples; filetype=fastq

  Dataset EGAD00001005157

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX024_SA604X9XB02417_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005148

• iPSC and iNeuron RNAseq, chip-seq and single cell CRISPR activation

  Dataset includes 1) RNAseq for Bob_Ngn2 cell differentiation from iPSC to iNeuron stage (time point 0, 24, 48 and 96 hours). 2) Bob_Ngn2 cell line chip-seq (H3K4me3, H3K4me1, H3K27me3, H3K9me3, H3K27ac, H3K36me3) for both iPSC and iNeuron stage with 3 replicates at each time point. 3) Single cell CRISPR activation experiment with 96 endogenous genes.

  Dataset EGAD00001010050

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX024_SA604X9XB02417_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005147

• Exome reads

  This dataset contains WES data (.bam files) and associated phenotype information from 10 patients included in our microbiome study who went on to anti PD-1 immunotherapy for the treatment of metastatic melanoma at the University of Texas MD Anderson Cancer Center. Both tumor and matching germ line normal were sequenced on each patient using Illumina HiSeq 2500. The average coverage was 283X in tumors and 135X in germline (tumor+germline overall:209, Range: 0-1552).

  Dataset EGAD00001003797

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX019_SA604X7XB02089_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 36 samples; filetype=fastq

  Dataset EGAD00001005150

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX_014_SA604X6XB01979_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 3 samples; filetype=fastq

  Dataset EGAD00001005154

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX018_VOA11019SA_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 24 samples; filetype=fastq

  Dataset EGAD00001005156

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX050_PBC04573_001

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005166

• Sequencing data for study Dissociation of solid tumour tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses for library TENX057_SA535X5XB02887_002

  Single-cell RNA-sequencing data generated using the 10X genomics chromium platform, comprising patient derived xenograft, cell line, and primary tumour data. This includes different digestion conditions (37C collagenase vs 6C cold protease) and FACS sorting for live, dying, and dead cells. 12 samples; filetype=fastq

  Dataset EGAD00001005175

• Analysis of the Whole Transcriptomes of Human Testis with Complete Spermatogenesis and of Human Testes with Sertoli Cell-Only Syndrome

  Sertoli cell-only syndrome is severe form of human male infertility in which most seminiferous tubules appear to lack all spermatogenic cells, including spermatogonial stem cells (SSCs). However, a few small tubule segments of some patients have active spermatogenesis and, thus, functional stem cell niches and SSCs. Normally SSCs replicate, migrate and refill adjacent empty niches, but this does not appear to occur in SCO syndrome. We hypothesized that this failure occurs because most niches are dysfunctional. As Sertoli cells are essential to formation of these niches, we used RNAseq to compare the transcriptomes of human testes with qualitatively normal (complete) spermatogenesis (n=4) with the transcriptomes of human testes with SCO syndrome (n=7). We then focused our analysis on the expression of transcripts that bioinformatic analyses identified as Sertoli cell signature transcripts. Results show that Sertoli cells in SCO testes express abnormally low levels of GDNF, FGF8 and BMP4, all of which are important regulators of mouse SSCs and/or progenitor spermatogonia. Sertoli cells in SCO testes express significantly reduced levels of transcripts for proteins that polarize the Sertoli cell plasma membrane and regulate the trafficking of cell adhesion and gap junction proteins in and out of that plasma membrane.

  Study phs001777

• Single Cell and Tissue Level Functional Genomics Analysis of Astrocyte-Related Mechanisms in Taupathy

  This data is the first part of a larger single cell and tissue level functional genomics analysis of dementias with tau pathology.  Cellular resolution will clarify the role of glial genes and pathways in neurodegenerative disease. This includes understanding the role of microglia and astrocytes in neurodegenerative disorders characterized by Tau protein pathology. To achieve a refined view of microglial neuroinflammatory signaling in tau-associated neurodegeneration, we performed a functional genomic analysis that integrated time-course gene expression data from mouse models expressing human mutant MAPT (the tau gene) with single nuclear sequencing data obtained from patients with frontotemporal dementia with Tau protein pathology (Pick’s disease). This included microglia-specific gene expression data obtained from single nuclear sequencing of postmortem frozen precentral gyrus samples collected from 16 total individuals, including 8 subjects with clinical diagnosis of behavior variant frontotemporal dementia and neuropathological diagnosis of Pick’s disease (Tau protein pathology) and controls (n=8). Our findings present detailed molecular profiles of disease-associated microglial transitions over the course of tau-associated neurodegeneration. Furthermore, we demonstrate overlap between microglia profiles obtained from precentral gyrus of patients with Pick’s disease with those up-regulated during the neurodegenerative stage in mice expressing human MAPT mutations.

  Study phs002197

• A Chromatin Accessibility Atlas of the Developing Human Telencephalon

  Gene expression differs between cell types and regions within complex tissues such as the developing brain. To discover regulatory elements underlying this specificity, we generated genome-wide maps of chromatin accessibility in nine anatomically-defined regions of the developing human telencephalon. Additionally, we defined the histone modification landscape of the prefrontal cortex and generated chromatin accessibility maps of its upper and deep layers. We predicted a subset of open chromatin regions (18%) that are most likely to be active enhancers, many of which are dynamic with 26% differing between early and late mid-gestation and 28% present in only one brain region. These predicted regulatory elements (pREs) are enriched proximal to genes with expression differences across developmental stages, regions, and cortical laminae; they harbor distinct sequence motifs that suggest potential upstream regulators. We leveraged this atlas to predict and validate novel regulatory elements of genes that control cortex laminar identity and genes associated with autism spectrum disorder (ASD). These include enhancers proximal to FEZF2 and BCL11A that were validated in mouse, and an enhancer of ASD gene SLC6A1 containing two functional de novo mutations in individuals with ASD whose enhancer function we validated via CRISPRa. We also include data for transcription factor binding in mid-fetal cortex tissues, using CUT&RUN methods.

  Study phs002033

• Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer

  Immunotherapy has produced disappointing results in recurrent ovarian cancer (OC). However, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based on the analysis of treatment-naive tumours. To understand the immunobiology of recurrent cancers, and their evolution, we profiled a total of 697 OC tumour samples (566 primary and 131 recurrent including 69 patient-matched samples) from 595 patients of five independent multi-institutional cohorts. By capturing heterogeneous TIL distributions, we identified four immune phenotypes associated with differential prognosis, TILs states and TILs:myeloid networks, which dictate malignant progression after chemotherapy and recurrence. Notably, recurrent tumours recapitulate the immunogenic landscapes of original cancers. Mirroring inflamed human OC, preclinical recurrent Brca1mut tumours maintained activated TILs:dendritic cells (DCs) niches but evaded immune control through COX/PGE2 signaling upregulation. Conversely, recurrent Brca1wt tumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuring Trem2/ApoEhigh TAMs and Nduf4l2high/Galectin3high malignant states. Our study highlights that persistent immunogenicity in recurrent OC is governed by the BRCA-dependent crosstalk between dissimilar myeloid cells and TILs. We propose new targets to modulate the malignant and TAM compartments which improve efficacy of standard of care chemotherapy in mouse OC models with HR deficiency.

  Study EGAS50000001069

• Exome_trios_in_patients_with_gastroschisis

  Gastroschisis (MIM 230750) is a herniation of the intestines through a defect of the abdominal wall lateral to the umbilicus (usually on the right side), and it is not covered by a membrane [Ledbetter, 2012]. Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. On the basis of clinical manifestations, epidemiologic charateristics, and the presence and type of additional malformations, gastroschisis could be considered a heterogeneous condition with no gene/s discovered yet. This congenital anomaly affects approximately 1-3 infancts per 10,000 live births [Calzolari et al.1995;Parker et al.,2010] Current knowledge about causative mutations/variants. To date, no single gene has been linked to gastroschisis. Some publications have tried to link this malformation to variants in genes (such as AEBP1 (adipocyte enhancer binding protein) gene [Feldkamp et al,. 2012] or the VEGF-NOS3 pathway [Lammer et al., 2008]. Previously, a Scribble mutant mouse model (circletail) was reported to exhibit gastroschisis, however recent studies demonstrated that the Scribble knockout fetus exhibits exomphalos phenotype of gastroschisis [Carnagham et al., 2013]. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002664

• Genomics of enteropathy associated T cell lymphoma (EATL)

  Enteropathy-associated T cell lymphoma (EATL) is a lethal and the most common neoplastic complication of celiac disease. In this study, we applied whole exome sequencing in 69 EATL tumors to define the genetic landscape of EATLs. The most frequently mutated gene in EATL was SETD2 (32% of cases), with loss of function mutations comprising a large proportion (41%) of those mutations. The JAK-STAT pathway was the most frequently mutated signaling pathway, with mutations in STAT5B being the most common, followed by JAK1, JAK3, STAT3, and the negative regulator of the pathway, SOCS1. We also identified mutations in NRAS and KRAS, as well as TP53 and TERT. Interestingly, the two types of EATL had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. Gene expression analysis of the two types of EATL identify robust differences in transcriptional profiles. We further modeled the effects of SETD2 loss in vivo by developing a T cell specific knockout mouse model. These mice manifested an expansion of γδ T cells that identify novel roles for SETD2 in T cell development and lymphomagenesis. Together, our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease, and may inform future classification schemes.

  Study EGAS00001001954

• Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

  The WD40-containing E3 ubiquitin ligase RFWD3 has been recently linked to the repair of DNA damage by Homologous Recombination (HR). Here we show that an RFWD3 mutation within the WD40 domain is connected to the genetic disease Fanconi anemia (FA). An individual revealed congenital abnormalities characteristic for FA. Cells from the patient, carrying the compound heterozygous mutations c.205_206dupCC and c.1916T>A in RFWD3, show increased sensitivity to DNA interstrand cross-linking agents in terms of increased chromosomal breakage, reduced survival and cell cycle arrest in G2 phase. The cellular phenotype is mirrored in genetically engineered human and avian cells by inactivation of RFWD3 or by introduction of the patient-derived missense mutation, and is rescued by expression of wildtype RFWD3 protein. HR is disrupted in RFWD3 mutant cells, caused by impaired relocation of mutant RFWD3 to chromatin and defective physical interaction with RPA. Rfwd3 knockout mice exhibit increased embryonic lethality, are sub-fertile, show ovarian and testicular atrophy and have a reduced life span in which they resemble other FA mouse models. Although mutation was detected in a single child with FA yet, we propose RFWD3 as a novel FA gene, FANCW, supported by cellular paradigm systems and an animal model.

  Study EGAS00001002440

• Comprehensive genomic profiles of small cell lung cancer

  We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. We found bi-allelic inactivation of TP53 and RB1 in nearly all the tumors analyzed, sometimes by complex genomic rearrangements. Two tumors with wild-type RB1 had evidence of chromothripsis leading to overexpression of Cyclin D1, revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumor suppressors TP53 and RB1 is obligatory in SCLC. We further discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In few cases, SCLC tumors exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduced the number of tumors and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

  Study EGAS00001000925

• A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia

  The PRDM13 (PR Domain containing 13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a novel, recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia, normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the co-occurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.

  Study EGAS00001005878

• T cell landscape definition by multi-omics identifies galectin-9 as novel immunotherapy target in chronic lymphocytic leukemia (CLL)

  Failure of immunotherapy after applying checkpoint inhibitors or CAR-T cells is linked to T cell exhaustion. Here, we explored the T cell landscape in chronic lymphocytic leukemia (CLL) by single-cell omics analyses of blood, bone marrow and lymph node samples of patients and spleen samples of a CLL mouse model. By single-cell RNA- sequencing, mass cytometry (CyTOF), and multiplex image analysis of tissue microarrays, we defined the spectrum of phenotypes and transcriptional programs of T cells and and their differentiation state trajectories. We identified disease-specific accumulation of distinct regulatory T cell subsets and T cells harboring an exhausted phenotype exclusively in the CLL lymph node tissue. Integration of TCR data revealed a clonal expansion of CD8+ precursor exhausted T cells, suggesting their reactivity for CLL cells. Interactome analyses identified the TIM3 ligand Galectin-9 as novel immunoregulatory molecule in CLL. Blocking of Galectin-9 in CLL-bearing mice slowed down disease development and reduced the number of TIM3 expressing T cells. Galectin-9 expression correlated with shorter survival of CLL patients. Thus, Galectin-9 contributes to immune escape in CLL and represents a novel target for immunotherapy.

  Study EGAS00001006864

• GnRH Agonist-Induced Ovarian Suppression and Ovarian Steroids in PMDD and Controls

  In this study, lymphoblastoid cell line cultures (LCLs) from women with premenstrual dysphoric disorder (PMDD) and asymptomatic controls were compared via whole-transcriptome sequencing (RNA-seq) during untreated (ovarian steroid-free) conditions and after estradiol and progesterone treatment. In untreated LCLs, pathway analysis of the LCL transcriptome revealed, among others, over-expression of ESC/E(Z) complex genes (an ovarian steroid-regulated gene silencing complex) with significant overexpression of MTF2, PHF19, and SIRT1 (P<0.05) in cells from women with PMDD compared with controls. Finally, mRNA expression of several ESC/E(Z) complex genes were increased by progesterone in controls only, and decreased by estradiol in PMDD LCLs.

  Study phs001344

• Investigation of MMBIR DNA Repair in Normal and Cancer Human Cells

  Microhomology-mediated break-induced replication (MMBIR) is a DNA repair pathway in which template switching at microhomology was proposed to promote complex genomic rearrangements (CGRs) that contribute to cancer. Yet, the extent of MMBIR activity in genomes is poorly understood due to difficulty in directly identifying MMBIR events by whole genome sequencing (WGS). This study aims to detect MMBIR events in human cancer genomes and to determine their frequency and complexity in tumors as compared to their non-tumor counterparts. This study contains WGS data from matched tumor and normal samples, and cultured cell line control WGS datasets that are not currently represented in other cancer genome databases.

  Study phs002237

• Tissue Sampling and Biorepository to improve Cancer Cell Therapy

  This study focuses on the elucidation of determinants of response and resistance to anti-CD19 CAR T-cells in large B-cell lymphoma. Plasma samples were collected prior to treatment and serially post CAR T-cell infusion. Pre-treatment and relapse tumor samples were also obtained as available. Germ-line DNA isolated from Peripheral Blood Mononuclear Cells (PBMCs) was collected for all patients when available. Circulating tumor DNA (ctDNA) and tumor DNA were sequenced using a target hybrid capture oligonucleotide pool. RNA-Seq was also performed on tumor isolated RNA. The authors identified several recurrent genomic alterations associated with relapse, and identified molecular thresholds that were predictive of response.

  Study phs003145