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• Presence of fungal infection in brains of patients with Parkinsons disease (PD)

  Isolation of fungi in infected neural tissues in patients with Parkinson's disease. Here we used next generation sequencing of Internal Transcribed Spacer (ITS) regions, by PCR amplicons (NGS ITS amplicon analysis).

  Study EGAS00001003644

• CAF-S3 subset in human breast and ovarian cancers

  Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. By combining 6 well-known stromal markers, we identify four CAF subsets (CAF-S1 to CAF-S4) in human breast and ovarian cancers.

  Study EGAS00001003344

• SNP array study in Autism Spectrum Disorder patients

  The aim of this study was to investigate two ancestral inversions (inv17q21.31 and inv8p23.1) in Autism Spectrum Disorder (ASD) patients. We have performed SNP array in order to genotype these inversions using the package scoreInvHap.

  Study EGAS00001005606

• germline variants in children with hematological cancer

  Trio parent-child whole exome sequencing has been used to identify cancer predisposing syndrome (CPS) in our pediatric patients with hematological cancer, and it was identified in 3.8% of the total number of patients(131).

  Study EGAS00001006907

• ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas

  We have sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas

  Study EGAS00000000075

• Oral Microbiome in Esophageal Adenocarcinoma

  The purpose of our study was to assess the influence of oral microbiota on the development of esophageal cancer. Our preliminary case-control studies reported a global alteration of foregut microbiome in esophageal adenocarcinoma with the strongest changes found in the oral microbiome. We hypothesise that commensal oral bacteria are capable of activating or degrading carcinogens in cigarette smoke and therefore may contribute to esophageal carcinogenesis. We conducted a prospective study nested in two large US cohorts, to determine whether oral microbiota are associated with subsequent esophageal adenocarcinoma.

  Study phs001527

• NHLBI TOPMed: Children's Health Study (CHS) Integrative Genetic Approaches to Gene-Air Pollution Interactions in Asthma (GAP)

  The Integrative Genetic Approaches to Gene-Air Pollution Interactions in Asthma (GAP) study was proposed to use an innovative genetics approach in mice and humans to identify novel variants that interact with traffic-related pollutant exposures to affect lung function phenotypes and the risk of childhood asthma. The study participants were enrolled from the original southern California Children's Health Study (CHS). In the TOPMed project, seven Hispanic White participants who did not have asthma history were included in the WGS analysis.

  Study phs001602

• Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

  We describe recurrent chromothripsis and structural variation of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ~25% of patients (‘chr21amp’). Chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. Here we provide high-depth whole genome sequencing (WGS) in five chr21amp BP-MPN cases, to a median coverage of 81x [range 77-86] and purity 79% [range 58-88%].

  Study EGAS00001007483

• CUT&Tag sequencing of ZFHX4 and H3K27ac in midbrain dopaminergic neurons.

  CUT&Tag sequencing of the transcription factor ZFHX4 and the histone mark H3K27ac was performed in midbrain dopaminergic neurons (mDANs) derived from induced pluripotent stem cells. This epigenomic approach enabled the identification of ZFHX4 binding sites in this specific cellular context. Comparing the CUT&Tag profiles of ZFHX4 and H3K27ac provided insights into epigenetic landscapes in mDANs and revealed whether ZFHX4 exhibits patterns similar to the active transcription mark H3K27ac. Finally, enrichment analysis of the identified peaks highlighted potential primary targets of ZFHX4 in mDANs.

  Study EGAS50000001112

• ScRNA-seq of PBMC and whole blood samples reveals a dysregulated myeloid cell compartment in severe COVID-19

  In a dual-center, two-cohort study, we performed single-cell RNA-sequencing of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time. This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

  Study EGAS00001004571

• Convergent somatic evolution from early life in a germline ribosomopathy

  Clonal tracking of stem cells and their progeny by whole genome sequencing permits exploration of evolutionary genetics in human disease. In this study, we performed phylogenetic reconstruction of haematopoiesis using somatically acquired mutations in 323 single haematopoietic stem and progenitor cell-derived colonies from 10 individuals with an inherited disorder of ribosome assembly, Shwachman-Diamond syndrome. We observed numerous clonal expansions, with recurrent acquisition of mutually exclusive mutations (EIF6, TP53, RPL5, RPL22, PRPF8, chromosomes 7 and 15) in multiple different clones in utero or early childhood converging on the p53-dependent nucleolar surveillance pathway that monitors ribosome integrity. In contrast to clones carrying biallelic TP53 mutations, genomes derived from colonies carrying mono-allelic TP53 mutations displayed no increase in mutation burden or specific mutational signatures. Our study highlights striking loss of clonal diversity with convergent somatic evolution on the p53-dependent nucleolar surveillance pathway from early life to offset the deleterious effects of a germline mutation in a Mendelian haematopoietic disorder.

  Dataset EGAD00001009061

• Relapse CHL study

  Classical Hodgkin Lymphoma (CHL) is characterized by a complex tumor microenvironment (TME) that supports disease progression. While immune cell recruitment by Hodgkin and Reed–Sternberg (HRS) cells is well-documented, the role of non-malignant B cells in relapse remains unclear. Using single-cell RNA sequencing (scRNA-seq) on paired diagnostic and relapsed CHL samples, we identified distinct shifts in B cell populations, particularly an enrichment of naïve B cells and a reduction of memory B cells in early-relapse compared to late-relapse and newly diagnosed CHL. The enrichment of naïve B cells in early relapse biopsies was confirmed in independent validation cohorts using scRNA-seq and immunohistochemistry. Notably, naïve B cells in early-relapse samples exhibited high expression of LGALS9, an immunosuppressive molecule known to interact with T cell immunoglobulin and mucin domain 3 (TIM-3) on regulatory T cells (Tregs). Cell-cell interaction analysis revealed the importance of interactions between LGALS9+ naïve B cells and TIM-3+ Tregs in the early-relapse setting. Spatial analysis by imaging mass cytometry confirmed close proximity of LGALS9+ naïve B cells with TIM-3⁺ CD4⁺ T cells and HRS cells, pointing to their role in shaping an immunosuppressive niche. Our findings highlight a previously unrecognized population of LGALS9⁺ naïve B cells with immunoregulatory potential in early-relapse CHL and provide new insights into the spatial and transcriptional architecture of the relapsed TME in CHL.

  Study EGAS00001008222

• DATA FILES FOR SJAMLM7

  DATA FILES FOR SJAMLM7

  Dataset EGAD00001000259

• Medulloblastoma WES

  WES for tumor and normal samples

  Study EGAS50000000261

• The data access committee for "Validation of cfDNA fragmentome analyses for early detection of liver cancer"

  Dac EGAC00001003543

• Deep_sequencing_of_melanoma_for_driver_mutations

  Deep sequencing of melanoma for driver mutations

  Study EGAS00001000857

• Human Lung Tissue eQTL Study

  Genetic risks underlying respiratory diseases (e.g. COPD and asthma) are carefully studied by large genome-wide association studies (GWAS), where many loci were identified. In the post-GWAS era, the main challenge is to find the causal genes and pathways in GWAS-nominated chromosomal regions and to characterize etiology mechanism. The Lung eQTL Consortium is an international effort to systematically capture the genetic architecture of gene expression regulation in human lung. By studying lung specimens from 1,103 individuals of mostly European ancestry, we report a large number of genetic variants affecting gene expression in the lung, or lung expression quantitative trait loci (eQTL). These lung eQTLs will serve as an important resource to aid in the understanding of the molecular underpinnings of lung biology and its disruption in disease.

  Study phs001745

• IMCISION RNAseq

  RNA sequencing could be performed on all 32 baseline and 30 on-treatment primary tumor biopsies. Based on gene-set enrichment analysis, the epithelial to mesenchymal transition signature was enriched in baseline tumors of patients without MPR, though its expression was insufficient to predict ICB response. Baseline and on-treatment IFNγ and T-cell signature expression (Z-score) were not significantly higher in patients with an MPR.­­­ Baseline primary tumor hypoxia-associated gene expression in IMCISION did not predict ICB response. However, on-treatment biopsies of MPR tumor samples showed significantly lower hypoxia gene expression when compared to non-MPR samples. Moreover, in a paired analysis of baseline and corresponding on-treatment samples, a significant decrease of hypoxia-related gene expression was observed in MPR biopsies, while this decrease was absent in non-MPR biopsies.

  Study EGAS00001005454

• Biomarkers for Noise-Induced Sleep Disruption

  This project aims to investigate gene expression biomarkers for noise-induced sleep disruption and cognitive changes. The project is a sub-study, part of the larger ASCENT COE project 86 designed to test the ability of broadband pink noise to serve as a countermeasure for sleep loss from simulated aircraft noise. Gene expression research was sponsored by the Federal Aviation Administration.

  Study phs003932

• March 2019 data update for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  March 2019 data update for cord blood CD34+CD38-, CMP, GMP, MEP, monocyte, erythroid precursor, B cell and primary AML total blasts reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium. This dataset contains data for samples: CEMT0158 CEMT0159 CEMT0160 CEMT0161 CEMT0162 CEMT0163 CEMT0164 CEMT0165 CEMT0166 CEMT0167 CEMT0168 CEMT0169 CEMT0170 CEMT0171 CEMT0172 CEMT0189

  Dataset EGAD00001004950

• Recursive splicing in long vertebrate genes

  Recent studies have shown that expression of many genes with exceptionally long introns in the mammalian brain can be perturbed by regulatory factors linked to neurodevelopmental or neurodegenerative disorders1-3, suggesting unique regulatory mechanisms. Here we identify functional recursive splice sites (RSS) in long introns of genes expressed in the brain. These RSS are highly conserved in genes with extreme length across diverse vertebrate species and permit step-wise removal of long introns via recursive splicing. Recursive splicing requires initial definition of a “recursive exon” that is located downstream of RSS, and most often contains premature stop codons. Moreover, we show that RSS create a splicing switch driven by splice site competition in order to distinguish primary mRNA isoforms from alternative isoforms that are prevalent in long genes. The recursive exon is not detectable in the dominant mRNA isoform due to recursive splicing, but is completely included when cryptic promoters or other cryptic exons are used. Thus, by coupling inclusion of recursive exons with the use of cryptic elements, RSS act to distinguish new mRNA isoforms emerging from long genes.

  Study EGAS00001001170

• MINCR is a MYC-induced lncRNA able to modulate MYC’s transcriptional network in Burkitt lymphoma cells

  Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.

  Study EGAS00001001199

• Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk paediatric cancer

  Zero Childhood Cancer is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Utilising tumour and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumours from high-risk paediatric cancer patients, we identified 968 reportable molecular aberrations (39.9% in WGS and RNAseq, 35.1% WGS-only, 25.0% RNAseq-only). 93.7% of patients had at least one germline or somatic aberration, 71.4% had therapeutic targets and 5.2% had a change in diagnosis. WGS identified pathogenic cancer-predisposing variants in 16.2% of patients. In 76 CNS tumours, methylome analysis confirmed diagnosis in 71.1% and contributed to a change of diagnosis in two cases (2.6%). To date 43 patients have received a recommended therapy, 38 of whom could be evaluated. A small but encouraging proportion of 31% showed some evidence of clinical benefit. Comprehensive molecular profiling resolved the molecular basis of virtually all high-risk cancers, which in some cases has significant clinical impact.

  Study EGAS00001004572

• Mutations in SPINK2 induce azoospermia

  Azoospermia, characterized by the absence of spermatozoa in the ejaculate is a common cause of male infertility with a poorly characterized etiology. Exome sequencing analysis of two azoospermic brothers allowed the identification of a homozygous splice mutation in SPINK2, encoding a serine protease inhibitor believed to target acrosin, the main sperm acrosomal protease. In accord with these findings we observed that homozygous Spink2 KO male mice had azoospermia. Moreover, despite normal fertility, heterozygous male mice had a high rate of morphologically abnormal spermatozoa and a reduced sperm motility. Further analysis demonstrated that in the absence of Spink2, protease-induced stress initiates Golgi fragmentation and prevents acrosome biogenesis leading to spermatid differentiation arrest. We also observed a deleterious effect of acrosin overexpression in HEK cells, effect that was alleviated by SPINK2 coexpression confirming its role as acrosin inhibitor. These results demonstrate that SPINK2 is necessary to neutralize proteases during their cellular transit towards the acrosome and that its deficiency induces a pathological continuum ranging from oligoasthenoteratozoospermia in heterozygotes to azoospermia in homozygotes.

  Study EGAS00001002450

• MalariaGEN case-control study in the Gambia

  MalariaGEN case-control study in the Gambia.

  Study EGAS00000000026

• SCLC ctDNA sequencing

  In this study we have sequenced the ctDNA of 28 Small Cell Lung Cancer patients in the TP53 gene, each sample has been sequenced twice.

  Study EGAS00001003984

• SCC ctDNA sequencing

  In this study we have sequenced the ctDNA of 28 Squamous Cell Carcinoma patients in the TP53 gene, each sample has been sequenced twice.

  Study EGAS00001003987

• The mutational landscape and its longitudinal dynamics in relapsed and refractory Hodgkin lymphoma

  In classical Hodgkin-lymphoma (cHL), only a few cases recur, and only a limited fraction of patients is primary-refractory to standard-polychemotherapy. Underlying genomic features of unfavorable clinical courses remain sparsely characterized. Here, we investigated the genomic characteristics of primary-refractory/relapsed cHL in contrast with long-term-responders (LTR). In total, data from 84 samples were submitted.

  Study EGAS50000000149

• Novel Gene-Environment Regulatory Circuit in Chamber-Specific Growth of Perinatal Heart

  We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscle biopsies exhibited mitochondrial hyperplasia with decreased complex VI activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.

  Study phs002725

• Single Cell Omics Resolves Transcriptional Alterations in Sjogren's Syndrome

  Single cell omics resolves transcriptional alterations in Sjogren's Syndrome. This data compares the single cell transcriptional profiles of the minor salivary glands between Sjogren’s Syndrome patients and non-Sjogren’s Syndrome subjects. Portions of this data were reported in two separate publications: Huang & Perez, et al., 2021 Nature Medicine and Yin, et al., 2021, Frontiers in Immunology . 

  Study phs002446

• GWA Study of Oral Cavity, Pharynx and Larynx Cancers in European, and North and South American Populations - CIDR

  There is striking geographical variation in head and neck cancer (HNC) incidence globally. Some of the highest incidence rates have been observed in Southern and Eastern Europe and South America. The goal of this project is to assess susceptibility loci across and within ancestral backgrounds, using the All of Us array. Ten studies have come together in this initiative.

  Study phs002503

• RNA-Seq analysis of cocaine use disorder in Brodmann Area 9

  We aimed to identify cocaine use disorder associated changes in gene expression in the Brodmann Area 9 subregion of the human prefrontal cortex. RNA-sequencing was performed in N=13 individuals with and N=12 individuals without CUD. The individuals are originating from a cohort of N=42 individuals where DNA methylation (DNAm) levels were previously analyzed using the EPIC array.

  Study EGAS50000000150

• Detection of causative structural variants using long read whole genome sequencing in patients with non-syndromic autism spectrum disorder

  This study involved performing long read whole genome sequencing using Oxford Nanopore Technology platform on to detect causative structural variants in patients with non-syndromic autism spectrum disorder. This study was performed on 23 such children in whom prior karyotyping, Fragile-X analysis (in males), chromosomal microarray and whole exome sequencing did not identify a causative variant.

  Study EGAS50000000842

• Bevacizumab plus erlotinib in advanced solid cancers with Krebs cycle gene mutations: A multicenter phase II study

  Targeting aberrant metabolism in tumors with alterations in genes encoding Krebs cycle enzymes, a central component of glucose metabolism, is a promising therapeutic strategy. These tumors rely on aerobic glycolysis and promote VEGF-dependent angiogenesis; furthermore, EGFR signaling enhances aerobic glycolysis. This phase 2 trial evaluated bevacizumab and erlotinib in patients with solid tumors harboring Krebs cycle gene mutations.

  Study EGAS50000001243

• DATA FILES FOR SJPHALL

  DATA FILES FOR SJPHALL

  Dataset EGAD00001000163

• This DAC takes care of requests for data for the Swiss epigenetic colorectal cancer cohort study, SWEPIC

  Dac EGAC00001003471

• Dataset for the spanish node

  Dataset for the spanish node

  Dataset EGAD50000000884

• DATA FILES FOR SJCPC-WGS

  DATA FILES FOR SJCPC-WGS

  Dataset EGAD00001001065

• WGS minibam files for SJLIFE

  WGS minibam files for SJLIFE

  Dataset EGAD00001003396

• Exploring the Genomic Dark Matter of Neurodevelopmental Disorders

  Neurodevelopmental Disorders (NDDs) are a group of disorders that typically manifest early in development and may give rise to impaired cognition, communication, adaptive behavior, and psychomotor skills. This study aims to take a more comprehensive view into the genomic landscape of structural variants implicated in NDDs with intellectual disability (ID). We have evaluated the genome of families with a genetically unsolved severe NDD via optical genome mapping. This study identified likely pathogenic or pathogenic structural variants in known NDD genes, including BCL11A, OPHN1, PHF8, SON, and NFIA. Data is available in VCF format, following the standard filtering settings in Bionano Access and available as "variants_combine_filters_inMoleRefine1.vcf" files.

  Study phs002937

• Genetic Analysis of Epidermal Inclusion Cysts

  The goal of this study was to identify a potential driver of epidermal inclusion cysts, or epidermoid cysts, (EICs) in human skin. Individuals were recruited at EIC excision appointments made a priori, with no exclusion criteria. Fresh biopsies and saliva were taken from consented patients, and DNA harvested immediately. Whole exome sequencing was performed (150-bp paired end reads) to 200X in tissue and 80X in saliva via Illumina NovaSeq 6000 sequencer. Identification of somatic mutations was performed using GATK best practices. Somatic variants in the NEK9 gene were found in 12/14 cases sequenced, with clustering of variants within the RCC1 and kinase domains of the protein.

  Study phs003776

• Copy-choice recombination during mitochondrial L-strand synthesis causes DNA deletions

  Mitochondrial DNA (mtDNA) deletions are associated with mitochondrial disease, and also accumulate during normal human ageing. The mechanisms underlying mtDNA deletions remain unknown although several models have been proposed. Here we use deep sequencing to characterize abundant mtDNA deletions in patients with mutations in POLG, the gene encoding mitochondrial DNA polymerase, and show that these have distinct directionality and repeat characteristics. Furthermore, we recreate the deletion formation process in vitro using only purified mitochondrial proteins and defined DNA templates. Based on our in vivo and in vitro findings, we conclude that mtDNA deletion formation involves copy-choice recombination during replication of the mtDNA light strand.

  Study EGAS00001003148

• RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood

  We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions.

  Study EGAS00001004768

• The Genomic Landscape of Endocrine Resistant Advanced Breast Cancers: Paired Pre- and Post-endocrine Therapy Samples.

  The genomic evolution of breast cancers exposed to systemic therapy and its effects on clinical outcome have not been broadly characterized. We integrated the genomic sequencing of 1918 breast cancers, including 1501 hormone receptor-positive tumors, with detailed clinical information and treatment outcomes. Functional mutations in ERBB2 and loss-of-function mutations in NF1 were more than twice as common in post-endocrine therapy tumors compared to treatment-naive tumors. Additional alterations in the MAPK pathway (EGFR, KRAS among others) and in estrogen receptor transcriptional regulators (MYC, CTCF, FOXA1 and TBX3) were also more common compared to hormonal therapy-naive tumors. To determine whether candidate genomic lesions in the MAPK pathway and estrogen receptor transcriptional regulators were present prior to therapy or whether such lesions arose under the selective pressure of therapy, we performed whole-exome sequencing in select patients who had adequate samples acquired prior to and after progression on endocrine therapy. In total, 95 specimens corresponding to 30 treatment-naive primary tumors, 35 post-treatment tumors, and 30 normal samples were sequenced from 30 patients with endocrine-resistant metastatic breast cancer.

  Study phs001674

• Mutational bias in spermatogonia impacts the anatomy of regulatory sites in the human genome

  Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (>=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.

  Study EGAS00001005366

• Luminal breast epithelial cells from wildtype and BRCA mutation carriers harbor copy number alterations commonly associated with breast cancer

  Cancer-associated mutations have been documented in normal tissues, but the prevalence and nature of somatic copy number alterations and their role in tumor initiation and evolution is not well understood. Here, using single cell DNA sequencing, we describe the landscape of CNA variants in >48,000 breast epithelial cells from women with normal or high risk of developing breast cancer. Individual cells with one or two of a specific subset of CNAs (e.g. 1q gain and 16q, 22q, 7q, and 10q loss) are detectable in almost all breast tissues and, in those from BRCA1 or BRCA2 mutations carriers, occurs prior to loss of heterozygosity (LOH) of the wildtype alleles. These CNAs, which are among the most common associated with ductal carcinoma in situ (DCIS) and malignant breast tumors, are enriched almost exclusively in luminal cells and are generally absent from basal myoepithelial cells. Allele-specific analysis of the enriched CNAs reveals that each allele was independently altered, demonstrating convergent evolution of these CNAs in an individual breast. Tissues from BRCA1 or BRCA2 mutation carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, LOH of BRCA1 or BRCA2, and multiple breast cancer-associated CNAs in addition to one or more of the common CNAs in 1q, 10q or 16q. Notably, cells with intermediate levels of CNAs were not detected, arguing against a stepwise gradual accumulation of CNAs. Overall, our findings demonstrate that chromosomal alterations in normal breast epithelium including from high risk women, link early stage CNAs to clonally expanded tumor genomes .

  Study EGAS00001007716

• 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

• Pooled scRNA-seq of iPSC-derived neural stem cells from ADHD and control individuals

  This dataset comprises paired-end FASTQ files from single-cell RNA sequencing (scRNA-seq) of neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs). The iPSCs were reprogrammed from somatic cells (keratinocytes, PBMCs, or lymphoblastoid cell lines) collected from individuals diagnosed with attention-deficit hyperactivity disorder (ADHD) and age-matched healthy controls (ages 6–18 years). Reprogramming was carried out using the non-integrative Sendai virus system (CytoTune-iPS 2.0, Thermo Fisher Scientific), introducing OCT3/4, SOX2, KLF4, and cMYC. iPSCs were cultured in Essential 8 medium on vitronectin and underwent rigorous quality control including immunocytochemistry, qRT-PCR, mycoplasma testing, and SNP genotyping (Illumina Global Screening Array). NSCs were generated using a standardized neural induction protocol and validated via qRT-PCR and immunostaining for markers including PAX6, SOX2, NESTIN, TUJ1, and FOXG1. Two independent scRNA-seq multiplexed experiments were performed: Experiment 1 (ADHD: n = 7; Control: n = 6) and Experiment 2 (ADHD: n = 9; Control: n = 7). Samples were pooled and demultiplexed using the Ensemblex algorithm, incorporating prior genotype data. After quality control filtering (>500 unique RNA molecules per cell), 30,433 single-cell transcriptomes were retained. Differential gene expression analysis was conducted to identify transcriptional signatures associated with ADHD compared to controls.

  Study EGAS00001008169

• Standard epigenome mapping in human epithelial cells of the digestive and urogenital organs [ ChIP-Seq ]

  The aim of this study is to participate in International Human Epigenome Consortium (http://ihec-epigenomes.org/), through disclosure of quality reference epigenome profiles in normal and diseased cells obtained from multiple Japanese people.

  Study JGAS000165

• Standard epigenome mapping in human epithelial cells of the digestive and urogenital organs [RNA-Seq ]

  The aim of this study is to participate in International Human Epigenome Consortium (http://ihec-epigenomes.org/), through disclosure of quality reference epigenome profiles in normal and diseased cells obtained from multiple Japanese people.

  Study JGAS000080