16767 results for "sec+and+unspecified+malignant+neoplasm"

in 44.94 milliseconds.

• Colorectal cancer organoid-stroma biobank cohort

  In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived tumor organoids (PDTOs) show enormous potential for preclinical testing, however, purely epithelial cultures features including the ‘consensus molecular subtypes’ (CMS) are largely eradicated. To better reflect the cell type heterogeneity, we established the CRC organoid-stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAFs) from 30 patients. Whole exome sequencing and transcriptome analysis in various in vitro and in vivo contexts was performed to study the influence of the TME on the CRC phenotype.

  Dataset EGAD00001011173

• Timing the Philadelphia chromosome and trajectory to chronic myeloid leukaemia

  We sequence >1000 whole genomes from 9 patients with CML, providing the largest sequencing dataset for this cancer. We reconstruct phylogenetic trees using somatic mutations and infer BCR::ABL1 timing and tumour growth rates. We correlate mutation landscapes and clonal trajectories with clinical features.

  Dataset EGAD00001015353

• RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor

  This dataset comprises raw RNA sequencing from inflammatory (TPP) macrophages that were treated with the MEK inhibitor PD-0325901 (100nM or 500nM) or vehicle control (n=3 donors). MEK inhibitor or vehicle control was added on day 4 and cells were harvested on day 6 and lysed. RNA was extracted from cell lysates using an AllPrep DNA/RNA Mini Kit (Qiagen). Sequencing libraries were prepared from 10ng RNA using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara) following the manufacturer’s instructions. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 and the libraries were sequenced on a NextSeq500. Raw data are provided as 50 bp paired-end Illumina reads.

  Dataset EGAD00001011337

• Single-cell RNA-seq of peripheral blood mononuclear cells in classic Hodgkin lymphoma

  Abstract: Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (paired samples from cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors.

  Dataset EGAD00001011360

• Naive TCR V, D and J gene usage frequencies

  This dataset contains gene usage matrices calculated from the processed productively rearranged bulk TCR sequences from peripheral blood CD4+ T cells from 103 subjects with celiac disease and 103 control donors. The files contain per sample V, D and J gene usage frequencies for TRA and TRB sequences. Unique rearrangements were quantified with Alakazam in gene mode. More details about processing steps are found in the linked publication. The dataset also contains an accompanying metadata file (csv).

  Dataset EGAD50000002726

• Naive BCR V, D and J gene usage frequencies

  This dataset contains gene usage matrices calculated from the processed productively rearranged bulk BCR sequences from peripheral blood B cells from 102 subjects with celiac disease and 102 control donors. The files contain per sample V, D and J gene usage frequencies for IGH, IGK and IGL sequences. Unique rearrangements were quantified with Alakazam in gene mode. More details about processing steps are found in the linked publication. The dataset also contains an accompanying metadata file (csv).

  Dataset EGAD50000002727

• Whole Genome Sequencing of Liver Cancers

  Genomic alterations driving tumorigenesis result from the interaction of environmental exposures and endogeneous cellular processes. With a diversity of risk factors including viral infection, carcinogenic exposures and metabolic diseases, liver cancer is an ideal model to study these interactions. Whole genome sequencing of liver tumors identified 10 mutational signatures showing distinct relationships with environmental exposures, replication and transcription. Transcription-coupled damage was specifically associated with the liver-specific signature 16 and alcohol intake. Flood of indels were identified in very highly expressed hepato-specific genes, likely resulting from replication-transcription collisions. Reconstruction of sub-clonal architecture revealed mutational signature evolution during tumor development exemplified by the vanishing of aflatoxin-B1 signature in African migrants. These findings shed new light on the natural history of liver cancers.

  Dataset EGAD00001003281

• Genomic alterations in MM - BAM

  Tumor DNA was extracted from 100 bone marrow aspirate samples where CD138+ selection had been performed to enrich plasma cells from patients with multiple myeloma. Patient matched control DNA from either peripheral blood leukocytes or CD34+ stem cell harvests was also isolated. Both tumor and control DNA underwent library preparation using the Hyperplus kit (KAPA Biosystems) and were hybridized to baits for a targeted SeqCap myeloma panel (Nimblegen) encompassing 129 genes, regions for SNPs for copy number determination, and the IGH, IGK, IGL loci, as well as approximately 5 Mb surrounding the MYC locus. Samples were sequenced on a HiSeq2500 using 100 bp paired end reads. Resulting BAM files were returned along with annotations for somatic events including single nucleotide mutations, indels and structural rearrangements.

  Dataset EGAD00001004117

• Single-cell RNA sequencing on 11,138 single T cells from 12 colon and rectal cancer (CRC) patients

  Deep single-cell RNA sequencing data for 11,138 T cells from tumour, adjacent normal tissue and peripheral blood of treatment-naive CRC patients. The DATA ACCESS AGREEMENT is provided at https://github.com/zhangyybio/single-T-cell-data-access. Applicants can request access to the data by directly downloading it or by sending an email to cancerpku@pku.edu.cn. The process that is used to approve an application includes verifying the institution, participants and research purposes of the application. In general this process will take about two weeks. In principal, any academic research institutions complying with the laws and bioethic regulation policies of China will be approved.

  Dataset EGAD00001003910

• Long-read sequencing for cell-free DNA analysis (human)

  In this study, we compared the two long-read sequencing platforms, namely the single-molecule real-time sequencing by Pacific Biosciences and nanopore sequencing by Oxford Nanopore Technologies, for the analysis of cell-free DNA from plasma. Cell-free DNA from plasma samples of 31 pregnant women at different trimesters, 6 hepatitis B carriers, and 8 patients with hepatocellular carcinoma were sequenced with the two platforms.

  Study EGAS00001006328

• Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma

  TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier in this setting is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort (n=95) and determined their impact on survival.

  Study EGAS00001005617

• Discriminating Th17.1 cell driven sarcoidosis-like inflammation from relapse after anti-BCMA CAR T cells in multiple myeloma

  We present a case study on sarcoidosis-like flare-up after Idecabtagen Vicleucel (Ide-cel), a BCMA targeting CAR T cell therapy, and identified a Th17.1 driven autoimmune mechanism as the biological underpinning of this phenomenon using single-cell RNA-seq analysis. Furthermore, single-cell RNA-seq allowed to discriminate between immune-mediated changes and true relapse after CAR T cell treatment.

  Study EGAS00001006133

• SPECIAL: Dissecting the melanoma ecosystem one cell at the time during immunotherapy

  The aim of this study was to identify potential biomarkers of response to immunotherapy (anti-PD1-based) as well as gain understanding of the biological mechanism of therapy resistance (either intrinsic or acquired) in melanoma patients. Single cell RNA sequencing was performed from pre- and on-treatment (2-3 weeks after immunotherapy) metastatic biopsies from stage III and IV melanoma patients.

  Study EGAS00001006488

• Characterization of a novel MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line WXS derived

  The lack of a well-characterized model system for many subtypes of leukemia hinders the development of targeted therapy and immunotherapy. A novel in-house-made pediatric MEF2D-BCL9 fusion positive acute lymphoblastic leukemia cell line was characterized. This cell line is highly presentative for the major clone of the original material and thus a valuable resource to examine novel therapeutic for MEF2D fused patients.

  Study EGAS00001006801

• A single-cell transcriptional gradient in human cutaneous memory T cells restricts Th17/Tc17 identity

  We identified a gradated transcriptional program of coordinately regulated inflammation-suppressive genes in psoriatic resident memory T cells. This dataset includes bulk RNA-seq for CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, in human PBMCs. It also includes scRNA-seq of cutaneous immune cells from psoriasis patients before and during therapeutic IL-23 blockade.

  Study EGAS00001006716

• Identifying autosomal recessive mutations causing neurological disorders

  The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations

  Dataset EGAD00001000340

• Identification of rare variants associated with cardiovascular traits in Cilento isolates

  The aim of this project is to identify rare genetic variants of large effect implicated in complex diseases by focusing on the study of cardiovascular diseases and related quantitative traits in a well characterized isolated population in Cilento area, Italy. The reference panel has been selected carefully in order to maximize the imputation coverage and quality on the all population samples. The selected individuals should meet three criteria: selected individuals should be chip-genotyped and closely related to the maximum number of chip-genotyped individuals so as to maximize imputation coverage; relatedness between selected individuals should be minimal, so as to minimize redundancy in genetic information of the reference panel. We perform exome sequencing on samples from 250 individuals from the Campora and Gioi-Cardile populations.

  Dataset EGAD00001002195

• Heterogeneous metabolic signatures are linked to cancer cell differentiation in colorectal cancer

  Colorectal cancer (CRC) is characterized by functional intratumor heterogeneity that shares many similarites with the hierarchical organization of the normal intestinal epithelium. In order to relate transcriptional subtypes to functional tumor cell heterogeneity we applied scRNA-seq to 12 patient-derived CRC spheroid cultures. We identified shared expression programs that relate to intestinal lineages and revealed metabolic signatures that are linked to cancer cell differentiation. In addition, we validated and complemented sequencing results by quantitative microscopy using live-dyes and multiplexed RNA fluorescence in situ hybridization, thereby revealing metabolic compartmentalization and potential cell-cell interactions. Finally, we demonstrate functional differences between metabolically distinct lineage subtypes that might have strong implications for future treatment strategies of CRC.

  Dataset EGAD00001005524

• Follicular lymphoma shallow whole genome sequencing and targeted sequencing of lymphoma panel

  Stage I and stage III/IV Follicular lymphoma samples, shallow whole genome sequencing for copy number analysis and targeted capture sequencing for mutation and translocation analysis.

  Dataset EGAD00001008385

• Strand-seq of hematopoietic stem and progenitor cells along human aging

  Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics based on Strand-seq technology, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

  Dataset EGAD00001009402

• A Genome-Wide Association Study in Patients Experiencing Musculoskeletal Adverse Events on NCIC CTG Trial MA.27 Evaluating Aromatase Inhibitors as Adjuvant Therapy in Early Breast Cancer. A Collaboration Between the NIH Pharmacogenetics Research Network and the RIKEN Yokohama Institute Center for Genomic Medicine.

  Source of Patients The source of the patients for this genome-wide case control study was MA.27, which was conducted as a multi-cooperative group effort under the auspices of the NCI Breast Cancer Intergroup of North America. The NCIC Clinical Trials Group (CTG) serves as the coordinating group, with participation by the NCI-sponsored North Central Cancer Treatment Group, Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group, and Cancer and Leukemia Group B (CALGB). MA.27 involved postmenopausal women with histologically confirmed and completely resected invasive breast cancer with surgical margins clear of invasive carcinoma and DCIS in the following TMN categories (AJCC Version 6): pT1, pT2, pT3; pNx, pN0, pN1, pN2, pN3 (only when the sole basis is presence of 10 or more involved axillary nodes); MO. The primary tumor must have been ER and/or progesterone receptor positive. Patients were stratified by lymph node status at diagnosis, prior adjuvant chemotherapy, and trastuzumab use and were randomized to 5 years of adjuvant therapy with anastrozole or exemestane. The trial was activated on May 26, 2003, and reached its accrual objectives on July 31, 2008, after the randomization of 6827 North American patients, with the majority (79%) providing DNA and consent for genetic testing. Non-North American patients were also entered by the International Breast Cancer Study Group but they did not contribute DNA. From 2003 to December 21, 2004, patients also underwent a second randomization to celecoxib 400 mg twice daily or placebo but, after the entry of 1,622 patients, this treatment was discontinued because of reports of increased cardiovascular risk associated with celecoxib. Case Definition for Musculoskeletal Adverse Events Cases were defined to have had at least one of the following six MSAE): 1. pain - joint, 2. pain - muscle, 3. pain - bone, 4. arthritis, 5. joint - function, 6. musculoskeletal - other. Cases were required to have at least grade 3 toxicity, according to the NCI Common Terminology Criteria for Adverse Events v3.0, or go off treatment for any grade of the six MSAEs; and were required to have had an MSAE within the first two years (i.e., a MSAE occurring after 2 years was not be considered a case). Subjects were excluded from the case group who met the case definition while on celecoxib or in the three months after stopping celecoxib but subjects were allowed to be cases if they developed their first MSAE more than three months after stopping celecoxib. Study Design The design was a nested matched case-control study with two controls selected for each case. Random matching from the potential control group (i.e., risk-set sampling such that controls had at least the same length of followup as the timing of the case event) was done by matching the case on the following factors: 1. treatment arm (exemestane vs. anastrozole, blinded), 2. prior adjuvant chemotherapy (yes vs. no), 3. age at start of treatment (+/- 5 years), 4. Celecoxib allocation (yes vs. no). Attempts were made to exactly match each case with two controls according to the above criteria. If, however, controls could not be exactly matched, "close" matching was used to define a distance between each case and all potential controls in an optimal matching algorithm. Race is a potential confounding factor, and 94% of the MA.27 population is Caucasian, 3% are Black, 1% Asian, 1% American Indian, and 1% are of unknown race. Because there are so few non-Caucasian participants, was restricted to only Caucasians. Following identification of cases and controls, the list was sent to the CALGB Pathology Coordinating Office (PCO) at Ohio State University Medical Center for plating of the samples. Other patient factors that might influence the association of SNP genotypes with a MSAE, either as confounding factors or as effect modifiers, were included as investigational covariates. These include 1. body mass index (BMI), 2. bisphosphonate use, 3. fractures in past 10 years, 4. baseline ECOG performance status, 5. prior hormone replacement therapy, 6. prior adjuvant radiotherapy, and 7. prior taxane treatment. An Honest Broker Process was utilized to ensure patient confidentiality. Genotype Assays and Quality Control A GWAS was performed with the Illumina Human610-Quad at the RIKEN Center for Genomic Medicine. The DNA for all of the samples were adjusted to a concentration of 50 to 100 ng/µL in a final volume of 50 µL. The 96-well plates were designed to have a unique distribution pattern with x duplicates per plate to evaluate genotype concordance. Samples with <98% call rate were removed from analyses. SNPs with ambiguous call will be excluded using the following criteria: 1. low signal intensity of each allele, 2. low cluster separation score, 3. SNP call rate <0.98, 4. SNPs with Hardy Weinberg Equilibrium p-value <0.001 were excluded. X-chromosome SNPs were used to validate female sex and quality control measures were examined across the different submitting centers. For all pairs of subjects, the percentage of matching genotypes were computed to screen for unexpected duplicate samples. All SNPs found to be associated with MSAE were subjected to visual inspection of the cluster plots to verify that the genotype clustering was adequate.

  Study phs000210

• Discovering the Genetic Basis of Cleft Palate: CIDR

  Cleft palate (CP) is a common craniofacial structural birth defect caused by the incomplete closure of the palate (the structure separating the oral and nasal cavities), resulting in feeding, speech, and hearing problems. CP accounts for 33% of all orofacial clefts (OFCs) or approximately 1 in 1500 babies born worldwide. Although CP is commonly grouped with other types of orofacial clefts (e.g. cleft lip or cleft with cleft palate), CP is embryologically and epidemiologically distinct, suggesting a unique etiology. The risk of CP recurrence in first degree relatives is over 50-fold higher than the population risk, suggesting a strong genetic component. However, there have been a dearth of genetic studies for CP. Three well-powered genome-wide association studies and meta-analysis have revealed only two associated loci, neither of which account for a large portion of the genetic heritability in any population. The goal of this study is to elucidate the genetic architecture of CP by performing whole genome sequencing of case-parent trios in a well-phenotyped, multi-ethnic cohort. 

  Study phs002220

• Chromoanasynthesis as a Cause of Jacobsen Syndrome

  Jacobsen syndrome (OMIM #147791) is a rare multisystem genomic disorder involving craniofacial abnormalities, intellectual disability, other neurodevelopmental defects and terminal truncation of chromosome 11q, typically deleting ~170 to >340 genes. We describe the first case of Jacobsen syndrome caused by congenital chromoanasynthesis, an extreme form of complex chromosomal rearrangement. Six duplications and five deletions occurred on one copy of chromosome 11q with microhomology signatures in the breakpoint junctions, indicating an all-at-once replication-based rearrangement mechanism in a gametocyte or early post-zygotic cell. Eighteen genes were deleted from the Jacobsen region, including KIRREL3, which is associated with intellectual disability. Patients of any age with abnormal immune function who have recurrent or unusual infections, whose blood tests show evidence of immune dysfunction, or who have GVHD, XSCID, CGD or LAD may be eligible for this study. Patients' parents, siblings, grandparents, children, aunts, uncles and first cousins of any age also may be included. Healthy normal volunteers between 18 and 85 years of age are recruited as controls.

  Study phs002036

• PAGE: The Charles Bronfman Institute for Personalized Medicine (IPM) BioMe BioBank

  The Institute for Personalized Medicine (IPM) BioMe Biobank is a consented, EMR-linked medical care setting biorepository of the Mount Sinai Medical Center (MSMC) drawing from a population of over 70,000 inpatients and 800,000 outpatient visits annually. MSMC serves diverse local communities of upper Manhattan, including Central Harlem (86% African American), East Harlem (88% Hispanic Latino), and Upper East Side (88% Caucasian/white) with broad health disparities. IPM BioMe Biobank populations include 28% African American, 38% Hispanic Latino predominantly of Caribbean origin, 23% Caucasian/White. IPM BioMe Biobank disease burden is reflective of health disparities with broad public health impact. Biobank operations are fully integrated in clinical care processes, including direct recruitment from clinical sites waiting areas and phlebotomy stations by dedicated Biobank recruiters independent of clinical care providers, prior to or following a clinician standard of care visit. Recruitment currently occurs at a broad spectrum of over 30 clinical care sites. This study is part of the Population Architecture using Genomics and Epidemiology (PAGE) study (phs000356).

  Study phs000925

• The Genetic Basis of Progression in Multiple Sclerosis

  This study examined the genetic determinants of multiple sclerosis (MS) severity in an international cohort of people with MS assembled by the International Multiple Sclerosis Genetics Consortium (IMSGC) and the MultipleMS Consortium. A total of 12,584 people with MS of European ancestry were included in the main genome-wide association study (GWAS). Participants were enriched for older individuals with longer disease duration (mean age 51.7 years and mean disease duration 18.2 years). All individuals were whole-genome genotyped on the Illumina Global Screen Array (GSAMD-24v2-0). Imputation was performed using the Haplotype Reference Consortium reference panel. The primary outcome was the age-related MS severity score. All individuals had at least 1 expanded disability status scale (EDSS) measure. When multiple EDSS scores were available, the last one was selected to calculate the age-related MS severity score.Of those 12,584 people with MS, this data release includes 4,623 participants recruited from non-European sites in the US, Canada and Australia. This release includes individual-level genotype and phenotype files necessary to replicate our GWAS of MS severity, including covariates.

  Study phs002929

• ARRA - NHLBI Lung Cohorts Sequencing Project: Genetic modifiers of

  The major goal of this project is to apply second generation resequencing technology to identify disease causing variants influencing pediatric and adult lung diseases in a collection of two longitudinal population cohorts of cystic fibrosis patients that have been well characterized for a comprehensive set of clinical traits. In Phase I, exome sequencing was performed on 43 cystic fibrosis patients with early Pa infection and 48 cystic fibrosis patients with late Pa infection to identify variants influencing the time to onset of Pa infection. In Phase II, additional exomes were added to the study, to reach a total of 91 individuals with early Pa infection and 96 with late Pa infection. The majority of the 340 subjects of Phase II do not have a Pa infection phenotype, but instead have a pulmonary function phenotype (121 severe vs. 124 mild impairment) as determined by the survival corrected Kulich FEV percentile of Corey et al. A small minority have intermediate phenotypes and/or show severe decline in lung function during childhood.

  Study phs000254

• Kids First: Genomics of Orofacial Clefts in the Philippines

  Orofacial clefts (OFCs) are the most common craniofacial structural birth defect in humans caused by incomplete formation of the upper lip and/or the palate. Over 4,000 children in the Philippines are born with an OFC every year, and the Filipino OFC birth prevalence rate of 1 in 500 live births is one of the highest in the world. Genome-wide association studies support a multifactorial etiology for OFCs, but common variants only account for up to ~25% of the heritable risk in any one population. Sequencing studies in diverse populations is essential to fully understand the genetic architecture of OFCs. The study goals of the Kids First project are to sequence a collection of case-parent trios from the Philippines, in order to identify de novo mutations and inherited rare variants, and understand the population differences in common variant signals in the Philippines versus other populations. Approximately 373 trios from the Philippines were selected for whole genome sequencing (WGS) as part of this Gabriella Miller Kids First project.

  Study phs002595

• Adoptive Cell Therapy of Autologous T cell Receptor-Engineered T Cells Targeting the p53 Neoantigens in Human Solid Tumors

  Adoptive T cell therapy (ACT) using T cell receptor (TCR)-engineered T cells can mediate regression of advanced human cancers. How TCR-transduced T cells change post-ACT in vivo is currently not well understood. We screened 78 patients for TP53 mutations by whole exome sequencing and whole transcriptome sequencing. Of the 78 patient samples, 49 patient samples were previously reported (phs001003) and 2 additional patients were reported in phs002735. In this accession we report the sequencing data of remaining 23 patients and include 6 additional samples from previously published patients. Additionally, we treated a patient with chemo-refractory breast cancer that expressed mutant p53 R175H with autologous T cells transduced with an allogeneic TCR targeting p53 R175H with human leukocyte antigen (HLA) restriction of A*02. The patient had a partial response for 6 months with 55% tumor regression. The T cells from the infusion product and the peripheral blood T cells at 6 weeks post-ACT were analyzed using 10X single cell transcriptome analysis.

  Study phs002928

• Study of Tumor Recurrence Related to the Expression of the PAX3-FOXO1 Oncogenic Transcription Factor in Fusion-Positive Rhabdomyosarcoma

  Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive pediatric soft tissue cancer characterized by a recurrent 2;13 chromosome translocation. This translocation generates a PAX3-FOXO1 (P3F) fusion gene, which encodes a chimeric transcription factor with oncogenic activity. Using a human myoblast system that models targeted therapy directed against P3F, we demonstrated that the expression of the fibroblast growth factor 8 (FGF8), a direct transcriptional target of P3F, is necessary and sufficient for PAX3-FOXO1-independent tumor recurrence in addition to be required for the tumorigenic activity of primary tumors expressing P3F. In addition, we showed that FGF8 is expressed in human rhabdomyosarcoma cell lines that express P3F. We also demonstrated that FGF8 contributes to their proliferation and transformation in vitro, and is sufficient to maintain their oncogenicity after the loss of P3F expression. We suggest that targeting the expression of the PAX3-FOXO1 transcription factor can generate resistance and recommend that additional anticipated therapeutic approaches, such as targeting FGF8 pathway, may avoid this resistance mechanism.

  Study phs002344

• PETAL Repository of Electronic Data COVID-19 Observational Study (RED CORAL)

  To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic, 1480 consecutive adult inpatients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020 were studied.It was found that in a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.The PETAL Network central institutional review board at Vanderbilt University and the institutional review boards at each participating hospital approved the study or determined that the study was exempt from review. Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

  Study phs002363

• Adolescent Idiopathic Scoliosis (AIS) 1000 Exomes Study

  Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Although the Bracing in AIS Trial (BrAIST) recently demonstrated the effectiveness of bracing for preventing scoliosis progression in some patients, more than 20,000 children undergo major spinal fusion surgery at an annual cost of $3 billion. Spinal fusion surgery is a major operation with considerable risks and complications. Accurate methods of predicting curve progression are needed to develop personalized prevention strategies for those at high risk and to eliminate screening and treatment of those at low risk of progression. Previously identified risk factors for scoliosis curve progression include sex, age of onset, curve type, and presence of an underlying disorder. However, currently available algorithms for predicting AIS curve progression are inaccurate, possibly because the role of genetic factors has been largely unexplored. Because there is little a priori knowledge of the genetic variants involved in AIS pathology, an unbiased genome-wide approach is likely to provide the best opportunity to comprehensively identify disease-associated genes. This is a multicenter exome sequencing study of extreme cases with severe scoliosis.

  Study phs001677

• A Pilot Trial of Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in HLA Allo-Immunized Patients

  Platelet transfusion can be a life-saving procedure in preventing or treating serious bleeding in patients who have low and/or dysfunctional platelets. Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. We conducted a pilot trial to investigate the use of eculizumab to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. We hypothesized that when we treated patients having platelet refractoriness with eculizumab, platelet counts would increase to higher numbers after platelet transfusions, decreasing the risk of bleeding complications associated with having a low platelet count. The response of the treatment was assessed by the corrected platelet count increment (CCI) 10 - 60 min and 18 - 24 h post transfusion, and any requirement for subsequent platelet transfusions following eculizumab. Reference 1 (PMID: 32086819) contains the main results for this trial.

  Study phs003212

• Normal Pressure Hydrocephalus

  Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder of aging that is characterized by enlarged cerebral ventricles, gait difficulty, incontinence and dementia. It is a common disorder that occurs almost exclusively after the age of 60. About 1.3% of patients over the age of 65 and 9-14% of nursing home residents are thought to have iNPH. Unfortunately, more than 90% of these patients remain misdiagnosed or undiagnosed, in part because the symptoms of iNPH resemble the symptoms of other neurodegenerative diseases, and in part because many health care practitioners are unfamiliar with this disorder. The etiology of iNPH is not known. Scattered reports of familial cases of iNPH suggest a genetic origin, but the genes involved are unknown. To investigate this matter, we have used exome sequencing to look for genetic factors associated with iNPH. We find recurrent heterozygous mutations in 10 genes, nearly all of which show increased expression in the ciliated ventricular epithelium and/or choroid plexus. Many have previously been associated with the function of cilia. 

  Study phs002296

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000416

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000418

• Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

  Non-invasive acquisition of mRNA data from the skin can be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable levels of human mRNAs exist in SSLs, where the sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNA levels, and our results revealed that the SSL-RNAs predominantly comprised mRNAs derived from sebaceous glands, the epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal-differentiation���related genes, consistent with the results of previous reports. Further, we found that lipid-synthesis���related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is a promising strategy to understand the pathophysiology of skin diseases.

  Study JGAS000417

• Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

  Myasthenia gravis (MG) is a neurological disease caused by autoantibodies against neuromuscular-associated proteins. While MG is frequently developed in thymoma patients, the etiologic factors for MG are not well understood. Here, by constructing a comprehensive atlas of thymoma using bulk and single-cell RNA-seq, we identified ectopic expression of neuromuscular molecules in MG-associated thymoma (MG-thymoma). These molecules were originated from a distinct subpopulation of medullary thymic epithelial cells (mTECs), which we named neuromuscular mTECs (nmTECs). MG-thymoma also exhibited microenvironments dedicated to autoantibody production, including ectopic germinal center formation, T follicular helper cell accumulation, and type 2 conventional dendritic cell migration. Cell-cell interaction analysis also predicted the interaction between nmTECs and T/B cells via CXCL12-CXCR4. The enrichment of nmTECs presenting neuromuscular molecules within MG-thymoma was further confirmed by immunohistochemically and by cellular composition estimation from MG-thymoma transcriptome. Altogether, this study suggests that nmTECs play a significant role in MG pathogenesis via ectopic expression of neuromuscular molecules.

  Study JGAS000482

• HIV-phyloTSI: Subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data

  Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

  Study EGAS50000000895

• Linked-Read Whole Genome Sequencing Profiles Structural Variant Landscape of Gliomas with Barcode-Level Evidence

  Structural variants (SVs) play essential roles in glioma oncogenesis and offer prognostic insights, yet the SV landscape of gliomas has not been completely characterized due to previous technological limitations. To comprehensively profile the SV landscape of gliomas, we performed linked-read whole genome sequencing (LR-WGS) on 31 tumour samples from 20 glioma patients. Using barcode-level evidence, we validated known SVs and identified the presence of extrachromosomal DNA containing the EGFR sequence, which correlates with elevated EGFR expression. Additionally, we uncovered rare SVs affecting genes typically mutated by single nucleotide variants (SNVs), including those in the SWI/SNF chromatin remodeling complex. Our analysis also reveals selective chromosomal vulnerabilities to SVs, highlighting certain chromosomes as hotspots for SV accumulation. Collectively, our results demonstrate the utility of LR-WGS in accurately detecting SVs and thoroughly profiling SV landscapes using barcode-level evidence. The insights gained into the synergistic effects of SNVs and SVs on oncogenes further underscore the importance of integrating SV analysis when examining mutations in gliomas.

  Study EGAS50000000947

• Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer

  Determining response to therapy for patients with pancreatic cancer can be challenging. We evaluated methods for assessing therapeutic response using cell-free DNA (cfDNA) in plasma samples from 40 patients with metastatic pancreatic cancer as part of the CheckPAC trial (NCT02866383). Patients were evaluated before and after initiation of therapy using tumor-informed plasma whole-genome sequencing (WGMAF), and genome-wide cfDNA fragmentation profiles and repeat landscapes (ARTEMIS-DELFI). Of those assessed with WGMAF, molecular responders had a median overall survival (OS) of 319 days compared to 126 days for non-responders (HR=0.29, 95% CI=0.11–0.79, p=0.011). For ARTEMIS-DELFI, patients with low scores after therapy initiation had a longer median OS than patients with high scores (233 days versus 172 days, HR=0.12, 95% CI=0.046-0.31, p<0.0001). We validated ARTEMIS-DELFI in a separate cohort of 40 patients with pancreatic cancer who were part of the PACTO trial (NCT02767557). These analyses suggest that non-invasive mutation and fragmentation-based cfDNA approaches can identify therapeutic response of individuals with pancreatic cancer.

  Study EGAS50000000923

• EGA file encryption types

  EGA file encryption The European Genome-Phenome Archive (EGA) stands as a significant initiative in the field of genomics, facilitating the secure storage and sharing of vast amounts of genomic data. Jointly hosted by the Centre for Genomic Regulation (CRG) and the European Bioinformatics Institute (EMBL-EBI), the EGA offers a robust infrastructure for managing encrypted data, ensuring the privacy and integrity of sensitive genomic information. Both CRG and EMBL-EBI play pivotal roles in the EGA, each institution bringing unique expertise in managing different types of encryptions. EMBL-EBI EGACryptor encryption system, while CRG utilises Crypt4GH, resulting in two distinct encryption file types: cip and c4gh, respectively. How can I check the file encryption? To access your dataset of interest on the European Genome-Phenome Archive (EGA) and determine the corresponding encryption file extension, please follow these step-by-step instructions: Utilise the search or navigation features provided on the EGA website to locate the dataset you are interested in. Once you find the dataset webpage, click on the "Files" tab, typically located on the dataset's webpage. Upon reaching the "Files" tab, you will be presented with a table containing comprehensive information about the files associated with the dataset. This table will include various columns, such as "File Name," "Size," and "Location." The "Location" column is particularly relevant for determining the encryption file extension. Figure 1: File table showing all the information available for the files in a dataset. This table is specific for each dataset. To identify the encryption file extension corresponding to a specific file, locate the "Location" column in the table. If the file is archived in Spain, the file will have the .c4gh extension, indicating that it is encrypted using Crypt4gh. Conversely, if the file is archived in the UK, the encrypted file extension will be .cip, indicating the usage of EGACryptor for encryption. It is worth noting that a file can be available in both locations, meaning it will be accessible with both file extensions (.c4gh and .cip). This allows users to choose the encryption method that aligns with their preferred platform or analysis tools.

  Documentation check-encryption-type

• Field_effect_of_healthy_and_diseased_livers

  Recent work in the Campbell group has revealed somatic mutations present in normal, non-cancerous human skin. A subset of the mutations conferred selective advantages to the host cells, leading to clonal expansions and raising the risk for future cancer development. Capturing such somatic mutations in normal tissue is important to advance our understanding about carcinogenesis and could provide prospective medical insights. In this project, our goal is to detect somatic mutations in normal (pre-cancerous) liver tissue. Using Laser Microdissection technology, we will dissect individual liver lobules from patient samples and submit these to sequencing. For each patient sample, we aim to sequence multiple lobules to characterise the mutagenic burden. Samples will be taken from patients with different liver disease aetiologies, including alcoholism and obesity, with a view on distinguishing the prevalent mutation types occurring in each disease context. We will perform targeted sequencing, initially using the WTSI cancer panel. Later we aim to use a novel bait set that captures both cancer genes as well as genes relevant to the non-cancerous samples (ie. genes implicated in hereditary disorders, immune sequences).

  Study EGAS00001002382

• FetalQuant-SD: Accurate quantification of fetal DNA fraction by shallow-depth sequencing of maternal plasma DNA

  Noninvasive prenatal testing using massively parallel sequencing of maternal plasma DNA has been rapidly adopted in clinical use worldwide. Fetal DNA fraction in a maternal plasma sample is an important parameter for accurate interpretations of these tests. However, there is a lack of methods involving low-sequencing depth and yet would allow a robust and accurate determination of fetal DNA fraction in maternal plasma for all pregnancies. In this study, we have developed a new method to accurately quantify the fetal DNA fraction by analysing the maternal genotypes and sequencing data of maternal plasma DNA. Fetal DNA fraction was calculated based on the proportion of non-maternal alleles at single-nucleotide polymorphisms where the mother is homozygous. This new approach achieves a median deviation of 0.6% between predicted fetal DNA fraction and the actual fetal DNA fraction using as low as 0.03-fold sequencing coverage of the human genome. We believe that this method will further enhance the clinical interpretations of noninvasive prenatal testing using genome-wide random sequencing.

  Study EGAS00001001611

• Genomic Analyses Identify Recurrent MEF2D Fusions in Acute Lymphoblastic Leukemia

  Chromosomal rearrangements are initiating events in acute lymphoblastic leukemia (ALL). Here, using RNA-sequencing (RNAseq) of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1164 B-ALL cases identified 30 cases with MEF2D rearrangements which include an additional fusion partner, FOXJ2, thus MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age, and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitors treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukemia, for which new therapeutic approaches should be considered.

  Study EGAS00001001952

• The_genetics_of_thinness_compared_to_obesity

  The variation in weight within a shared environment is largely attributable to genetic factors. Whilst many genes/loci confer susceptibility to obesity, little is known about the genetic architecture of thinness. In this study we performed a genome-wide association study of 1,622 persistently thin healthy individuals (STILTS), 1,985 severe childhood onset obesity cases (SCOOP) and 10,433 population based individuals (UKHLS) used as a common set of controls. All participants were genotyped on the Illumina Core Exome array, including 551,839 markers and imputed to the combined UK10K and 1000G (phase3) reference panel. We contrast the genetic architecture of thinness with that of severe early onset obesity and explore whether the genetic loci influencing thinness are the same as those influencing obesity pr whether there are important genetic differences between them. 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 EGAS00001002624

• Genome-wide mutational consequences of nucleotide excision repair-deficiency through XPC deletion in a human adult stem cell culture

  Nucleotide excision repair (NER) is one of the main DNA repair pathways that protect cells against genomic damage. Deficiency in this pathway can contribute to the development of cancer and accelerate aging. NER-deficiency is an important determinant for cancer treatment outcome, as NER-deficient tumors are selectively sensitive to cisplatin treatment. While NER-deficiency has been linked to mutational Signature 5, not all NER-deficient tumors are characterized by a high Signature 5 contribution, illustrating the importance to further characterize the mutational consequences of NER-deficiency. Here, we analyzed the mutational profile of a human adult stem cell (organoid) culture that is deficient in NER through XPC deletion by CRISPR-Cas9 gene-editing, and subsequent whole-genome sequencing analysis of a clonally derived organoid. We found that XPC deletion results in an increase in base substitution load and specifically induces Signature 8 mutations, a mutational signature with previously unknown etiology. Presence of Signature 8 may, therefore, serve as a novel biomarker for NER-deficient tumors and could improve personalized treatment strategies.

  Study EGAS00001002681

• Comprehensive analyses of somatic TP53 mutation in tumors with variable mutant allele frequency

  Somatic mutation of the tumor suppressor gene TP53 is reported in at least 50% of human malignancies. Most high-grade serous ovarian cancers (HGSC) have a mutant TP53 allele. Accurate detection of these mutants in heterogeneous tumor tissue is paramount as therapies emerge to target mutant p53. We used a Fluidigm Access Array™ System with Massively Parallel Sequencing (MPS) to analyze DNA extracted from 76 serous ovarian tumors. This dataset has been made available to researchers through the European Genome-phenome Archive (EGA). Herein, we present detailed analyses of this dataset using HaplotypeCaller and MuTect2 through the Broad Institute’s Genome Analysis Toolkit (GATK). We also present comparisons of the ability to detect TP53 mutation by MPS and Sanger sequencing in these tumors. We anticipate that this TP53 mutation dataset will be useful to researchers developing and testing new software to accurately determine high and low frequency variant alleles in heterogeneous aneuploid tumor tissue. Further, the analysis pipeline we present provides a valuable framework for determining somatic variants more broadly in tumor tissue.

  Study EGAS00001002200

• Genetic_mechanisms_of_resistance_to_chemotherapy_in_breast_cancer

  Resistance towards chemotherapy is one of the main causes of treatment failure and deathamong breast cancer patients.The main objective of this project is to identify genetic mechanisms causing some breastcancer patients not to respond to a particluar type of chemotherapy (epirubicin) while otherpatients respond very well to the same treatment.In the project we will perform genome / exome sequencing of a selection of breast cancerpatients (n=30). These patients are drawn from a cohort where all patients have recievedtreatment with epirubicin monotherapy before surgical removal of a locally advanced breasttumour, and where all patients have been subjected to objective evaluation of the response tothe therapy.Subsequent to sequencing, we will analyse the data and compare with the clinical data foreach patient (object response to therapy). The main aim being to identify mutations that areassociated with resistance to epirubicin.Identification of mutations with strong predictive value, may have a direct impact on cancertreatment since it opens the possibility for genetic testing of a tumour, and desicion on whichdrug is likely to work best, prior to treatment start.

  Study EGAS00001000276

• Genome-wide prediction of human embryos

  BACKGROUND: Preimplantation genetic diagnosis (PGD) enables profiling of embryos for genetic disorders prior to implantation. The majority of PGD testing is restricted in the scope of variants assayed or by the availability of extended family members. While recent advances in single cell sequencing show promise, they remain limited by bias in DNA amplification and the rapid turnaround time (&lt;36 h) required for fresh embryo transfer. Here, we describe and validate a method for inferring the inherited whole genome sequence of an embryo for preimplantation genetic diagnosis (PGD). METHODS: We combine haplotype-resolved, parental genome sequencing with rapid embryo genotyping to predict the whole genome sequence of a day-5 human embryo in a couple at risk of transmitting alpha-thalassemia. RESULTS: Inheritance was predicted at approximately 3 million paternally and/or maternally heterozygous sites with greater than 99% accuracy. Furthermore, we successfully phase and predict the transmission of an HBA1/HBA2 deletion from each parent. CONCLUSIONS: Our results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.

  Study EGAS00001001020

• 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

• SNP array files, IDAT files, from 34 members of a Family with a high prevalence of psychosis

  We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder, and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with a high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (N=4), genotyping by genome-wide SNP array (N=33), whole-exome sequencing (N=4), and whole-genome sequencing (N=12). We performed genome-wide linkage analysis, family-based association analysis, and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1-33.2, LOD score= 4.11), a suggestive region that contains five candidate genes ASTN2, BRINP1, C5, TLR4, and TRIM32, previously associated to MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.

  Study EGAS00001004592

• Exome sequencing demonstrates a dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.

  Retinoic acid (RA) and arsenic target the PML/RARA driver of Acute Promyelocytic Leukemia (APL), their combination now curing over 95% patients. Here we report exome sequencing of 64 matched diagnosis/remission/relapses patients treated with historical RA/chemotherapy protocols. A first subgroup presents a high incidence of oncogenic mutations disrupting key epigenetic or transcriptional regulators (primarily WT1) or activating MAPK signaling at diagnosis. Relapses retain these cooperating oncogenes and exhibit additional oncogenic alterations and/or mutations impeding therapy response (RARA, NT5C2). The second group primarily exhibits FLT3 activation at diagnosis, which is lost upon relapse together with most other passenger mutations, implying that relapses derive from pre-leukemic PML/RARA-expressing cells that survived RA/chemotherapy. Accordingly, clonogenic activity of PML/RARA-immortalized progenitors ex vivo is only transiently affected by RA, but selectively abrogated by arsenic. Our studies stress the role of cooperating oncogenes in direct relapses and suggest that targeting pre-leukemic cells by arsenic contributes to its clinical efficacy.

  Study EGAS00001002893

• Somatic_mutation_profiling_of_intestinal_crypts_from_IBD

  In this project we want to investigate the role that somatic mutations in intestinal stem cells play in IBD. We will use laser capture microdissection to ascertain epithelial cells from an individual crypts/vilus. We will extract DNA from these and use a new low-input material library prep methods to make accurate libraries for sequencing. In this pilot phase of the project we will perform 15X whole-genome sequencing of a small number of crypts biopsied from four patients. Biopsies have been taken from inflammed and noninflammed patches to compare mutation rates and mutational signatures. We will also test if crypts from inflammed patches of a single patient are clonal (either within a given inflammed patch or across inflammed patches). We will quantify the rate of cancer driver mutations in inflammed and non-inflammed crypts. 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 EGAS00001002896

• Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

  Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ρ=-0.75, p&lt;2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.

  Study EGAS00001004664

• DERMATLAS__Porocarcinoma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are porocarcinomas.

  Study EGAS00001005720

• DERMATLAS__Poroma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are poromas.

  Study EGAS00001007705

• DERMATLAS__Hidradenoma_papilliferum_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are hidradenoma papilliferums.

  Study EGAS00001005715

• DERMATLAS__Leiomyosarcoma_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are leiomyosarcomas.

  Study EGAS00001007631

• DERMATLAS__Hidradenoma_papilliferum_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are hidradenoma papilliferums.

  Study EGAS00001005714

• DERMATLAS__Poroma_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are poromas.

  Study EGAS00001005759

• A plasma protein biomarker signature that differentiates acute rheumatic fever from related clinical presentations

  Acute Rheumatic Fever (ARF) is a systemic inflammatory condition triggered by Group A Streptococcus infection, with timely diagnosis critical to prevent Rheumatic Heart Disease. ARF pathogenesis is poorly understood and diagnosis is based on clinical criteria. Here, we compared ARF cases and well-defined controls from two Uganda cohorts. We identified a 5-protein signature that discriminates ARF patients from clinically-similar conditions (receiver operating characteristic-area under the curve (ROC-AUC)=1.0, n=18 definite ARF vs n=9 known alternate diagnosis; ROC-AUC=0.97, n=18 definite ARF vs n=13 unknown alternate diagnosis), which retained very good diagnostic value in a validation cohort (ROC-AUC=0.83 n=26 definite ARF vs n=13 unknown alternate diagnosis). Pathway analysis identified the epithelial-mesenchymal transition pathway as highly-associated with acute ARF, suggesting that tissue damage and repair is central to ARF pathogenesis. Our findings require further validation, yet highlight the potential for proteomics to identify clinically useful diagnostic biomarkers that would revolutionise ARF diagnosis and treatment.

  Study EGAS00001008381

• DERMATLAS__Leiomyosarcoma_WES

  irtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are leiomyosarcomas.

  Study EGAS00001007628

• DERMATLAS__Porocarcinoma_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are porocarcinomas.

  Study EGAS00001005721

• DERMATLAS__Tubular_adenoma

  IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are tubular adenomas.

  Study EGAS00001006686

• DERMATLAS__Tubular_adenoma_RNAseq

  IVirtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are tubular adenomas.

  Study EGAS00001006685

• RNA sequencing data of 257 samples from 106 patients with HR+/HER2- breast cancer treated with AC plus paclitaxel or letrozole plus ribociclib (SOLTI-1402 CORALLEEN trial)

  Early-stage Luminal B breast cancer is frequent and is a major cause of breast cancer death due to its poor prognosis. Our proposal aims to study the biology behind the sensitivity and resistance of Luminal B breast cancer to chemotherapy (CHT) or a non-CHT regimen composed of hormone therapy in combination with ribociclib, a CDK4/6 inhibitor. To accomplish this, we first completed the SOLTI-1402 CORALLEEN phase II trial, a study where 106 patients with early-stage Luminal B breast cancer were randomized to standard neoadjuvant CHT for 6 months, or neoadjuvant letrozole and ribociclib for 6 months. After treatment, patients underwent surgery. The primary results of the study, which showed that the response rate to letrozole+ribociclib was similar to CHT, was reported (Prat et al; Lancet Oncol). Tumor biopsies were available at baseline, week 3 and surgery. A total of 257 samples were analyzed using the Illumina TruSeq Stranded Total RNA w/Ribo Zero Gold with MiSeq in TGL (Sequencer NovaSeq S4/PE/100x).

  Study EGAS00001007060

• Modulation of the peripheral blood immune cell transcriptome by vitamin D3 supplementation in people with a first demyelinating event: a randomized placebo-controlled trial

  Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.

  Study EGAS00001007346

• DERMATLAS__Leiomyoma_WES

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are leiomyomas.

  Study EGAS00001007629

• DERMATLAS__Leiomyoma_RNAseq

  Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis. Many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive genetic analysis previoulsy, we propose to perform whole exome and transcriptome sequencing, from a range of body sites, to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles. The cases in this cohort are leiomyomas.

  Study EGAS00001007630

• Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling

  The estrogen receptor (ER) drives growth in ~70% of breast cancers, and endocrine therapies prevent recurrence. However, 30% of patients recur, with many fatal cases occurring late (after &gt;5 years), presenting a challenge due to their often non-proliferative nature and limited options. To study this, we generated slow-growing resistant cells that form small primary tumours but readily metastasize. Single-cell RNA sequencing (scRNAseq) revealed that endocrine therapy reprograms these cells, notably upregulating the Rac1 signalling component P-Rex1. We found in clinical cohorts that P-Rex1 in high in ER+ breast cancer. Intravital imaging demonstrated that Rac1 signalling is active in ER+ cells following endocrine therapy. Targeting the Rac1 pathway with small molecule inhibitors (NSC23766, R-ketorolac) reduced survival and motility in resistant cells, inhibited in vivo Rac1 activity, and reduced tumour burden when combined with tamoxifen in a drug-refractory patient-derived xenograft. This work identifies the P-Rex1/Rac1 axis, as a potential therapeutic target for late recurring ER+ breast cancer.

  Study EGAS00001008353

• RNAseq data to study PRPF6 regulated splice forms in colon cancer cell lines

  Alternative splicing plays critical roles in differentiation, development, and cancer (Pettigrew et al., 2008; Chen and Manley, 2009). The recent identification of specific spliceosome inhibitors has generated interest in the therapeutic potential of targeting this cellular process (van Alphen et al., 2009). Using an integrated genomic approach, we have identified PRPF6, an RNA binding component of the pre-mRNA spliceosome, as an essential driver of oncogenesis in colon cancer. Importantly, PRPF6 is both amplified and overexpressed in colon cancer, and only colon cancer cells with high PRPF6 levels are sensitive to its loss. Our data clearly point to an important role for PRPF6 in colon cancer growth and suggest that a better understanding of its role in alternative splicing in colon cancer is warranted. To determine the specific alternative splice forms that PRPF6 regulates in colon cancer, we plan three experiments: 1. The first involves knocking down expression of PRPF6 in two different cancer cell lines with 3 different siRNAs, and then completing RNA-seq to determine the gene expression changes that occur relative to a non-targeting control siRNA. Because of the role for PRPF6 in pre-mRNA splicing, we especially want to quantify the changes in splice-specific forms of all genes genome-wide to identify genes whose splicing is altered upon PRPF6 knockdown. 2. The second involves immunoprecipitating PRPF6 from two different cancer cell lines and isolating any RNA that is bound to PRPF6, since PRPF6 is an RNA-binding protein. We then want to carry out RNA-seq to identify which RNA molecules co-immunoprecipitated with PRPF6. This will help us determine possible functions for PRPF6 in regulating colon cancer growth. 3. The third involves overexpressing PRPF6 in cell lines and then carrying out RNA-seq to identify any changes in splice-specific gene expression. This will allow us to determine whether increased PRPF6 expression is sufficient to drive alternative splicing changes.

  Dataset EGAD00001000817

• Brigham and Women's Hospital Multiple Sclerosis Genetic Collection

  The main objective of this GWA study is to identify Multiple Sclerosis (MS) susceptibility loci. Whole-genome association analysis was performed on 924 individuals genotyped on the Affymetrix 6.0 Genechip. The cohort consisted of 860 clinically diagnosed MS patients and 64 control subjects.

  Study phs000275

• Phase 2 Study of Pembrolizumab in Combination with Gemcitabine and Cisplatin as Neoadjuvant Therapy

  The purpose of the clinical trial (NCT02690558) is to evaluate whether adding pembrolizumab (Keytruda) to the combination of gemcitabine and cisplatin will improve shrinkage of the tumor before having a cystectomy, for people with muscle-invasive bladder cancer (MIBC).

  Study phs003452

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000664

• Comprehensive survey for the construction of an integrated database of food, gut microbiome, and health information (the "Sukoyaka Health Survey")

  We conducted a cohort-based study to investigate the association between the genetic background and diet/lifestyle in 59 healthy Japanese. We analyzed some participants living in Nagasaki. Shotgun metagenomic sequencing of fecal microbiome were analyzed.

  Study JGAS000681

• Application of organoid culture system of human gastrointestinal and thoracic cancer in genome medicine

  In order to establish preclinical models, we have established a kind of lung cancer tumoroids derived from a mucus-producing solid pulmonary adenocarcinoma patient. We performed whole exome sequencing and RNA sequencing to analyze genetic background of the tumoroids.

  Study JGAS000653

• Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma - RNA validation cohort

  This reposiroty contains bulk RNA data generated by Blood Cancer Research Group (Ostrava, Czech Republic) as a part of publication named "Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma" published in Hemapshere.

  Study EGAS50000001212

• Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma - WGS validation cohort

  This reposiroty contains bulk WGS data generated by Blood Cancer Research Group (Ostrava, Czech Republic) as a part of publication named "Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma" published in Hemapshere.

  Study EGAS50000001211

• Targeted sequencing data of regulatory regions in 200 Spanish ASD trios

  This dataset consists of genomic sequencing data obtained through targeted sequencing of regulatory regions ( 85,394 human cCREs from ENCODE v2, version 2, https://screenv2.wenglab.org/) in 200 ASD (Autism Spectrum Disorder) trios (father and mother unaffected and proband affected)(600 samples total). Sequencing was carried out at the Centre for Genomic Regulation (CRG), Barcelona, Spain. Uploaded files are .vcf (600 samples). The goals of our study were to detect de novo and inherited variants in ASD probands. Sequencing data were obtained in an Illumina NovaSeq6000 instrument.

  Dac EGAC50000000695

• Transcriptome sequencing, DNA methylation analysis, and SNP array analysis of acute lymphoblastic leukemia in Down syndrome

  Pathogenesis of acute lymphoblastic leukemia in Down syndrome (DS-ALL) is poorly understood. To investigate molecular basis of DS-ALL, we performed whole transcriptome sequencing, DNA methylation array, and SNP array analysis in 43 cases of DS-ALL.

  Study JGAS000147

• Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH

  Initially IDH1 mutant gliomas are shown to have IDH1 is deletions or amplifications at recurrence yielding a higher-grade tumor with a reprogrammed epigenome. We also report systematic selection for cells with IDH1 CNA in vitro and in vivo.

  Study EGAS00001002618

• Whole genome sequencing of Sinonasal hemangiopericytoma and patient derived cell line model

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using whole genome sequencing.

  Study EGAS50000000025

• Determinants of DNA methylation patterning in human placental development and trophoblast stem cell models.

  To assess whether the DNA methylation landscape of human trophoblast stem cells resembles an in vivo cell type, we used post-bisulfite adaptor-tag sequencing to measure genome-wide DNA methylation of preimplantation human trophectoderm and sorted first trimester cytotrophoblast.

  Study EGAS50000000661

• ERDERA WES reanalysis - DPF2 Batch 7

  This dataset comprises processed genomic data from 1000 samples, corresponding to 1000 whole-exome sequencing experiments from ERDERA Data Processing Freeze 2. Data files include CRAM, gVCF (containing short variants, copy number variants, and structural variants), RoH (BED), B-allele frequencies (BW), and variant IGV visualizations (XML). Associated phenotypic and pedigree information for all samples is also included.

  Dataset EGAD50000002503

• RNA sequencing of untreated and treated KRAS-mutated metastatic colorectal cancer PDX-derived organoids.

  RNA sequencing was performed on patient-derived xenograft (PDX)-derived organoid models of metastatic colorectal cancer (mCRC). The aim of this study was to characterize the transcriptional landscape of KRAS-mutant mCRC cells in response to therapeutic strategies targeting the EGFR and KRAS signaling pathways. Transcriptomic profiling was conducted following drug treatments to investigate molecular changes associated with single and combination therapies. A total of 24 samples were analyzed.

  Dataset EGAD50000002443

• WGS data of paediatric hyperdiploid B cell acute lymphoblastic leukemia (set3)

  The dataset includes FASTQ and BAM/CRAM files from diagnostic and matched remission (control) samples of eight hyperdiploid ALL patients (ALLT-364, ALLT-367, ALLT-368, ALLT-371, ALLT-377, ALLK-111, ALLT-382, ALLT-395). Sequencing libraries were made using PCR free-based WGS library preparation (PCR-), NEBNext® Ultra™ II DNA Library Prep Kit (Cat No. E7645). Both diagnostic (90x) and remission (30x) samples were sequenced using Illumina NovaSeq 6000.

  Dataset EGAD50000002427

• Dynamics of checkpoint receptors in γδ T cell subsets are associated with clinical responses during anti-PD-1 immunotherapies

  scRNA-seq data from circulating gamma delta T cells derived from healthy donors and patients with stage IV melanoma that either responded or did not respond to anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combination therapy. This dataset includes paired samples from these patients before and 3 months after the start of immunotherapy.

  Dataset EGAD50000001812

• Oxford Nanopore Adaptive Sampling WGS

  Eight samples were analyzed on an Oxford Nanopore MinION flow-cell, and to evaluate multiplexing, four samples were run together on one flow-cell on the P2 Solo device. Using adaptive sampling, we targeted 10 regions of different structural variant types, including deletions, translocations and complex rearrangements. MinION sequencing resulted in between 14.1-18.3 Gb of data per flow cell, with mean autosomal on-target coverage of 28.4x and off-target read depth coverage of 5.3x.

  Dataset EGAD50000001821

• Tapestri Sequencing Data of PDAC Autopsy Samples

  This dataset comprises single-cell DNA sequencing data for selected pancreatic ductal adenocarcinoma (PDAC) autopsy samples. It employs a targeted gene panel to identify single nucleotide variants (SNVs) and copy number variations (CNVs) using the Mission Bio Tapestri platform. The samples encompass primary and metastatic tissue from selected PDAC patients. This dataset includes 74 sample-level BAM files and 24 patient-level H5 files, generated by the MissionBio pipeline.

  Dataset EGAD50000001936

• ERDERA WES reanalysis - DPF1 Batch 4

  This dataset comprises processed genomic data from 1063 samples, corresponding to 1063 whole-exome sequencing experiments. Data files include CRAM, gVCF (containing short variants, copy number variants, and structural variants), RoH (BED), B-allele frequencies (BW), and variant IGV visualizations (XML). Associated phenotypic and pedigree information for all samples is also included.

  Dataset EGAD50000002389

• ERDERA WES reanalysis - DPF1 Batch 3

  This dataset comprises processed genomic data from 1243 samples, corresponding to 1243 whole-exome sequencing experiments. Data files include CRAM, gVCF (containing short variants, copy number variants, and structural variants), RoH (BED), B-allele frequencies (BW), and variant IGV visualizations (XML). Associated phenotypic and pedigree information for all samples is also included.

  Dataset EGAD50000002332

• ERDERA WES reanalysis - DPF1 Batch 2

  This dataset comprises processed genomic data from 733 samples, corresponding to 733 whole-exome sequencing experiments. Data files include CRAM, gVCF (containing short variants, copy number variants, and structural variants), RoH (BED), B-allele frequencies (BW), and variant IGV visualizations (XML). Associated phenotypic and pedigree information for all samples is also included.

  Dataset EGAD50000002331

• WGS data of paediatric ETV6::RUNX1 B cell acute lymphoblastic leukemia (set1)

  The dataset includes FASTQ and BAM/CRAM files from diagnostic and matched remission (control) samples of five ETV6::RUNX1 ALL patients (ALLT-380, ALLK-114, ALLT-388, ALLT-392, ALLT-394). Sequencing libraries were made using PCR free-based WGS library preparation (PCR-), using NEBNext® Ultra™ II DNA Library Prep Kit (Cat No. E7645). Both diagnostic (90x) and remission (30x) samples were sequenced using Illumina NovaSeq 6000.

  Dataset EGAD50000002285

• Long read whole genome sequencing data from brain postmortem tissue

  Dataset consisting of 172 whole genome sequencing runs from healthy controls and Parkinson's disease patients. The data was sequenced on Oxford Nanopore (PromethION) platform. The data has been mapped to T2T-CHM13v2.0 reference genome. The data processing pipeline is available on the following link: [https://zenodo.org/records/13385065](https://zenodo.org/records/13385065). The data is in CRAM format and subet of donors also have information on C (hydroxy)methylation (MM and ML tag). The reads are also phased (HP tag).

  Dataset EGAD50000001349

• HiChIP data and analysis in OCI-AML3

  Data and analysis of HiChIP assay of shZNF143 and shControl in OCI-AML3. CTCF was the ChIP antibody. Data files are paired-end reads in FASTQ format from the Illumina NovaSeq 6000 sequencer. Analysis files are paired-end bed files produced by FitHiChIP.

  Dataset EGAD50000001376

• Dataset of Study assessing the efficacy and safety of durvalumab plus olaparib plus fulvestrant in selected metastatic or locally advanced ER-positive, HER2-negative breast cancer patients.

  This dataset is made of 166 samples extracted from 1) FFPE blocks of the most recent biopsy (metastasis when applicable or primary tumor) of the breast tumor 2) Plasma samples and blood samples at baseline, at Day 1 Cycle2, Day 1 Cycle 3 and at progression or treatment discontinuation. Target sequencing has been perfomed using GREAT_A_v3 panel

  Dataset EGAD50000001665

• Human brain development single cell sequencing additional samples

  69 tissue samples from various parts of the developing human embryo brain were dissociated and single cells were collected and processed without bias for mRNA-seq using 10X chromium 3' protocol. Libraries were sequenced on Illumina NovaSeq and reads aligned against the human GRCh38 genome. This is an addition to EGAD00001006049 Human development single cell sequencing, consisting of samples added after the original submission to EGA, but included in final paper.

  Dataset EGAD50000001295

• RNA-seq libraries from FFPE samples using Illumina Ribo-Zero Plus kit

  RNA was extracted from FFPE human tissue samples and used to prepare RNA-seq libraries with the Illumina Stranded Total RNA Prep Ligation kit with Ribo-Zero Plus. cDNA synthesis was performed starting from 100 ng of DNA-free RNA. Libraries were amplified with 16 PCR cycles and sequenced in paired-end mode (2×150 bp) on the Illumina NextSeq 550 platform. Library quality was assessed with Bioanalyzer and Qubit.

  Dataset EGAD50000001553

• MissionBio single cell DNA and protein seq for 2 samples

  This dataset contains MissionBio Targeted single-cell DNA and Protein sequencing data from a primary sample and a patient-derived xenograft (PDX) model, which is used to investigate the clonal evolution in the FOXF1/FENDRR ALL subtype. All the 2 samples are in bam file type.

  Dataset EGAD50000001793

• WES analysis of DMD-ASD, DMD-ID and DMD-Control individuals for de novo and rare risk variants analysis

  This project generated a whole-exome sequencing (WES) dataset of 83 boys with a pathogenic variant in the DMD gene, along with WES data from the parents of 38 of them, totaling 159 samples. In addition to DMD, 12 boys also had ID (12 DMD-ID samples), 36 boys had ASD (DMD-ASD samples) and 35 did not present ID or ASD diagnosis (DMD-Control samples).

  Dataset EGAD50000001113