14429 results for ""Pennsylvania+German"+ACS+study+'Socius'+open+access"

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• Deep-Seq: Resistance to anti-EGFR therapy in colorectal cancer

  In this study we performed ultra deep sequencing of genes associated with anti-EGFR resistance, such as KRAS, BRAF, PIK3CA, and EGFR in 17 plasma-DNA samples from a total of 10 patients treated with anti-EGFR therapy.

  Dataset EGAD00001000688

• Metastatic breast cancer targeted gene screen (2014-09-24)

  The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations. This dataset contains all the data available for this study on 2014-09-24

  Dataset EGAD00001001018

• Whole Exome Sequencing of healthy Spanish individuals - VCF file

  The need for a detailed catalogue of local variability for the study of rare diseases within the context of the Medical Genome Project motivated the whole exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population.

  Dataset EGAD00001003101

• Metastatic breast cancer targeted gene screen (2017-05-11)

  The samples will be sequenced for a targeted panel of cancer relevant genes (n ~ 370) and analysed for somatic mutations. This dataset contains all the data available for this study on 2017-05-11.

  Dataset EGAD00001003330

• SNV vcf files for CPCG Subclonal Heterogeneity in multiple and single regions

  SNV calls generated using the MuTect-TITAN-PhyloWGS from the CPC-GENE Subclonal Heterogeneity study using single and multiple regions

  Dataset EGAD00001004433

• multi-region sequencing of tumor samples from PDAC patients

  This study includes 542 of multi-region sampled whole exome sequencing data from 83 pancreatic cancer patients in 6 individual experiments : Kras wildtype, local recurrence, treatment-naive (MetomeV2), radiotherapy plus chemotherapy (Radome), chemotherapy-only group (Treatome) and Proj_B-100-478.

  Dataset EGAD00001011109

• Expression data

  This dataset contains the RPKM and raw read counts of expression for all the individuals. This dataset was generated as part of the following study: Panousis et al (2019). Combined genetic and transcriptome analysis of patients with SLE: Distinct, targetable signatures for susceptibility and severity.

  Dataset EGAD00001005039

• Clinical phenotypes/covariates

  This dataset contains the clinical phenotypes/covariates information for all the individuals. This dataset was generated as part of the following study: Panousis et al (2019). Combined genetic and transcriptome analysis of patients with SLE: Distinct, targetable signatures for susceptibility and severity.

  Dataset EGAD00001005040

• Whole genome sequencing of ATCWGS42

  WGS of patient ATCWGS42, a patient who responded to BRAF/MEK targeted therapy but relapsed. This folder includes multi-region sequencing from the patient.

  Study EGAS50000001489

• Bulk WES Fastq Files for 103 Samples of Cornell-NCI DLBCL Genomic Project

  Paired-read fastq files were derived from standard Illumina WES NGS sequencing for 103 DLBCL biopsy samples. This is one of three datasets associated with the multi-platform NGS sequencing efforts of the Cornell-NCI DLBCL genomic study.

  Dataset EGAD50000001747

• RNASeq files for Mullighan TXVI dataset

  RNASeq files for paper titled "Prognostic and therapeutic significance of leukemia subtypes and minimal residual disease measurements in pediatric acute lymphoblastic leukemia treated with contemporary risk-directed trial: a cohort study"

  Dataset EGAD00001006609

• Exome sequencing data for 40 cases of alopecia areata and vitiligo

  Sequencing of independent unrelated cases of alopecia areata (total/ universal) and vitiligo (>10%, affected family member). DNA obtained from blood

  Study EGAS00001003831

• Genotyping NIGMS Chromosomal Aberration and Inherited Disorder Samples

  As part of an effort to correlate molecular copy number variation determinations with state of the art karyotype analyses, 716 samples derived from 697 individuals from the Chromosomal Aberrations and Inherited Disorders collections of the NIGMS Human Genetic Cell Repository were genotyped and analyzed for CNV determination by the Microarray Center at the Coriell Institute for Medical Research. Karyotyping is performed on all cell cultures in the Repository with reported chromosome abnormalities. The samples chosen for genotyping in this study are intended to represent a diverse set of copy number variants, but the selection was also weighted to over-sample commonly manifested types of aberrations. When available, the ISCN description of the sample based on G-banding and FISH analysis is included in the phenotypic data. Karyotypes for these cells can be viewed in the online Repository catalog (http://ccr.coriell.org/Sections/Collections/NIGMS/?SsId=8).

  Study phs000269

• Genetic analysis of patients with Inherited Retinal Dystrophies (IRDs) using next generation sequencing to identify the causative variants

  Genetic analysis of patients with Inherited Retinal Dystrophies (IRDs) was carried out by performing Whole Genome Sequencing (WGS). The main purpose of this study is to identify simple and complex mutations responsible for IRD in patients. WGS was performed on selected affected and unaffected individuals using the Illumina HiSeqX10. The reads were aligned to human genome 19 (hg19) and variant calling was performed using Genome Analysis Toolkit (GATK). The genotyping quality of single nucleotide variants (SNVs) and indels was assessed using the variant quality score recalibration approach implemented in GATK. Copy number variations (CNVs) were called using Genome STRiP and SpeedSeq. This large set of whole genome sequencing data from different ethnicity can be stored and shared through dbGaP. This data could serve as a source for checking frequencies of variants or the pathogenicity of selected variants in different ethnicities.

  Study phs001619

• University of Washington Developmental Single Cell Atlas

  We set out to generate a human cell atlas of both gene expression and chromatin accessibility using tissues obtained during development. In this study, we applied an assay for single cell profiling of gene expression based on three-level combinatorial indexing (sci-RNA-seq3) to 121 fetal tissue samples representing 15 organs, altogether profiling transcription in over 4 million single cells. In parallel, we devised an improved assay for single cell profiling of chromatin accessibility also based on three-level combinatorial indexing (sci-ATAC-seq3). We applied this method to 53 fetal tissue samples representing 15 organs, altogether profiling on the order of one million single cells. From these data, we identify and characterize diverse human cell types and annotate them with respect to marker genes, expression and regulatory modules. These data comprise a rich resource for the exploration of human biology.

  Study phs002003

• Genomic Analysis of Low Grade B-Cell Lymphoma

  We included tumors from 64 newly diagnosed or untreated Low Grade B-Cell Lymphoma (LGBCL) patients, consisting of SMZL (n = 48), NMZL (n = 6), EMZL (n = 2), LPL (n = 5), and B-NOS (n = 3) in this study. Samples were selected from cases consented to the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). RNA or DNA were extracted from 64 frozen LGBCLs tumors (with available matched germline DNA for N=61. For RNA sequencing, library preparation was done using the Illumina TruSeq RNA Exome Kit and sequenced with 100 nucleotide paired-end reads using the HiSeq 4000. For WES, library preparation was done using the Agilent SureSelect XT kit and sequenced with 100 nucleotide paired-end reads using the Illumina HiSeq 4000.

  Study phs002552

• RNA-Seq studies of Gene Expression in Cells and Networks in FI and ACC in Autism

  RNA-Seq studies of Gene Expression in Cells and Networks in FI (fronto-insular) and AC (anterior cingulate) cortex in Autism. We seek to understand the cellular bases of autism by using a new technology, RNA-Seq, to determine differences in gene expression in autopsy brains of subjects with well described autism versus age and sex matched neurotypical individuals. We have investigated two specific cortical areas involved in self-awareness and social reciprocity which are abnormal in autism and have found increased expression in a network of genes related to inflammation in autism group A, whereas the remaining cases, autism group B, have increased expression in a network of genes related to synapses. The current dbGaP study release includes RNA sequencing and phenotype data of n=27 subjects of African - American, Caucasian, or Hispanic origin.

  Study phs000609

• Notch Signaling and Efficacy PD-1/PD-L1 Blockade in Relapsed Small Cell Lung Cancer

  Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine (NE) cancer that accounts for approximately 15% of all lung cancer, with an annual incidence of more than 34,000 in the United States alone. SCLC is characterized by loss of function of p53 and RB and high tumor mutational burden, which suggests that these tumors could be immunogenic and respond to immune checkpoint blockade (ICB). However, the benefit from ICB in an unselected SCLC population is modest. In this study, we evaluated the genomic features associated with clinical outcomes in relapsed SCLC to gain insight into the underlying mechanisms of ICB response. Exome, RNA and TCR sequencing data from a prospective clinical trial of relapsed SCLC treated with durvalumab and olaparib and RNA-sequencing data for second cohort of relapsed SCLC cohort treated with nivolumab are included.   

  Study phs002176

• Female Infertility: Primary Ovarian Insufficiency

  Premature ovarian failure, or primary ovarian insufficiency (POI) is a phenotype of diminished or absent ovarian function occurring in 1-2% of reproductive aged women. Most cases occur spontaneously. Evaluation of the gametes in women with POI is difficult and invasive. Practitioners must often rely on indirect biomarkers of ovarian function and oocyte health, making it difficult to identify patients who may benefit from therapies allowing them to achieve pregnancy utilizing their own oocytes. This study will generate exome sequences from POI patients in an effort to elucidate the causes of unexplained POI and to better understand the normal processes of ovarian aging. A better understanding of the genetics of ovarian function may lead to new non-invasive tools for managing women's reproductive health, and direct better use of existing biomarkers in diagnosis, screening and predicting clinical outcomes.

  Study phs001174

• Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing

  Current methods available for pre-implantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos do not detect de novo. Detection of these types of mutations requires whole genome sequencing (WGS). In this study advanced massively parallel WGS was performed on three 5-10 cell biopsies from two blastocyst-stage embryos. Overall, greater than 95% of each genome was called and experimentally derived haplotypes and barcoded read data were used to detect and phase up to 82% of de novo single base mutations with a false positive rate of ~1 error per Gb. These results suggest that phased WGS using barcoded DNA could be used in the future as part of the PGD process to maximize comprehensiveness in detecting disease causing mutations and reduce the incidence of genetic diseases.

  Study phs000858

• Breast Cancer Susceptibility

  Genetic factors account for a large fraction of breast cancer risk and it is estimated that up to 30% of breast cancers have a heritable component. Inherited cancer susceptibility is associated with early-onset of malignancies in general. Although 20% of young women with breast cancer have germline mutations in the best understood breast cancer susceptibility genes, BRCA1, BRCA2 and TP53, in the remaining 80% of women with early-onset breast cancer, the genetic factors contributing to disease remain unexplained. By studying the extreme phenotype of women diagnosed at an early age there is enrichment for genetic factors that contribute to breast cancer. This study contains the whole exome sequence of 384 women diagnosed with invasive breast cancer prior to 40 years of age. Each of the subjects reported a family history of breast cancer and lacked mutations in BRCA1 and BRCA2.

  Study phs001017

• Genomic Factors Involved in Chromosome Rearrangements

  Approximately 15-20% of children referred for chromosomal microarray analysis (CMA) testing have a clinically relevant CNV that in many cases explains their phenotype. The goal of this study is to discover the genomic factors that mediate chromosome rearrangements and the phenotypic effects of chromosome rearrangements. We hypothesize that particular DNA sequences are susceptible to breakage and rearrangement. To this end, we fine-map chromosome breakage sites and analyze the DNA motifs that underlie double-strand breaks (DSBs). Our studies will also capture the genomic structure of breakpoint junctions, which will allow us to determine the mechanisms of DNA repair that shape different types of chromosome rearrangements. We also correlate chromosome rearrangements with clinical features to establish genotype-phenotype correlations. Defining critical regions of deletion or duplication is the first step to identifying candidate genes responsible for particular phenotypes.

  Study phs000845

• Deciphering Maternal-Fetal Crosstalk in the Human Placenta During Parturition Using Single-Cell RNA-Sequencing

  Labor is a complex physiological process requiring a well-orchestrated dialogue between the mother and fetus. However, the cellular contributions and communications that facilitate maternal-fetal crosstalk in labor have not been fully elucidated. In this latest version (#5), scRNA-seq was applied to decipher maternal-fetal signaling in the human placenta and chorioamniotic membranes during term labor. Samples were obtained from women who underwent spontaneous labor (n = 24) or who were delivered in the absence of spontaneous labor (n = 18) at term. Samples from previous versions (#1-3) of this study include the placental villous tree, basal plate, and chorioamniotic membranes of women across a range of pregnancy physiologic and pathologic conditions, including the processes of labor (term labor and preterm labor), and COVID-19 (version #3). Version #4 includes samples from the human myometrium during spontaneous term labor.

  Study phs001886

• Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

  This study describes a novel Immune Repertoire Sequencing technique, termed Molecular Identifier Clustering-based Immune Repertoire Sequencing (MIDCIRS), to reduce sequencing error while maintaining extremely high coverage and applies this technique to investigate the differential immune response to malaria between infants and toddlers. Despite a lower somatic hypermutation load, we found an unexpectedly high level of competency within the infant antibody repertoire, particularly the ability to diversify B cell clonal lineages upon acute infection. Detailed clonal lineage analysis encompassing lineages containing sequences from both pre- and acute malaria timepoints revealed an increase in somatic hypermutations upon acute infection. Further analysis on pre-malaria memory B cell containing lineages in toddlers who had previously been exposed to malaria provides evidence for the capacity of memory B cells to continue to mutate and isotype switch.

  Study phs001209

• Genomic Correlates of Response and Resistance to Immune Checkpoint Blockade in Solid Tumors

  Immune checkpoint inhibitors yield clinical benefit in many cancer types, but molecular predictors of response have not yet been robustly characterized. In this study, we pursued whole exome sequencing (WES) of pre-treatment tumors from patients treated with immune checkpoint therapies - including monoclonal antibodies targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). Using these data, we aim to apply computational pipelines for mutation-calling, neoantigen prediction, and other analyses to validate pre-existing hypotheses regarding response to immune checkpoint therapies and discover new relationships with greater power. Further, by pursuing genomic characterization of tumors from patients with a variety of cancer types, we hope to describe molecular features of intrinsically sensitive or resistant tumors that are both context-specific and shared across cancer types.

  Study phs001565

• Transcriptome of 2-Hydroxypropyl-Beta-Cyclodextrin Treatment in Niemann-Pick Disease Type C1

  Niemann-Pick type C (NPC) disease is a rare and fatal lysosomal storage disorder. Classically, children with NPC demonstrate neurological dysfunction with cerebellar ataxia, dysarthria, seizures, vertical gaze palsy, motor impairment, dysphagia, psychotic episodes, and progressive dementia. In general, adolescent and adult onset forms have a more insidious onset and slower progression. As part of a multi-omics approach to address the genetic architecture of NPC1 disease, we have recently completed a transcriptome analysis using 43 primary NPC1 patient-derived fibroblasts from an NIH-cohort study (NCT00344331) where extensive clinical data has been obtained regarding the natural history of the disease. Initial transcriptome analysis of this dataset demonstrated a set of 485 genes that are significantly upregulated in patient samples and subsequently downregulated in response to 2-hydroxypropyl-beta-cyclodextrin treatment. 

  Study phs002392

• Genome Sequencing of Pancreatic Ductal Adenocarcinoma at The Human Genome Sequencing Center of Baylor College of Medicine (HGSC-BCM)

  Pancreatic ductal adenocarcinomas (PDAC) is the 11th most common cancer in the USA but the 4th in fatalities. The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. We combined our capability to capture and enrich exome DNA with the next generation sequencing capacity to allow us to detect and characterize the somatic mutation profile of 24 patients with PDAC. Patient samples were collected by the Elkins Pancreatic Center in the Baylor College of Medicine Department of Surgery. Sequencing of the pancreatic ductal adenocarcinoma is one of the NHGRI Center Initiated Projects in progress in the Human Genome Sequencing Center at Baylor College of Medicine. These data are also contributed to an ICGC study and will be published with the ICGC collaborators.

  Study phs000516

• National Heart, Lung, and Blood Institute SNP Health Association Asthma Resource Project (SHARP)

  SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) is conducting a genome-wide analysis in adults and children who have participated in National Heart, Lung, and Blood Institute's clinical research trials on asthma. This includes 1041 children with asthma who participated in the Childhood Asthma Management Program (CAMP), 994 children who participated in one or five clinical trials conducted by the Childhood Asthma Research and Education (CARE) network, and 701 adults who participated in one of six clinical trials conducted by the Asthma Clinical Research Network (ACRN). There are three study types. The longitudinal clinical trials can be subsetted for population-based and/or case-control analyses. Each of the childhood asthma studies has a majority of children participating as part of a parent-child trio. The ACRN (adult) studies are probands alone. Control genotypes will be provided for case-control analyses.

  Study phs000166

• Dynamics of Genomic and Immune Responses During Primary Immunotherapy Resistance in Mismatch Repair Deficient Tumors

  We study a patient with dMMR lung cancer refractory to immunotherapy. Post-treatment tumor demonstrated compound heterozygous frameshift deletions located upstream of the kinase domain in the gene encoding JAK1 protein, downregulation of JAK1 and mediators of its signal transduction, and total loss of JAK1 phosphorylation. Importantly, one of the JAK1 mutations, despite not being detected in the pre-treatment tumor, was found at low variant allele frequency in the pre-treatment circulating tumor DNA, suggesting clonal selection of the mutation. This report provides the most detailed look yet of defective JAK1 signaling in the context of dMMR and immunotherapy-resistance. Together with observations of JAK1 frameshift indels being enriched in dMMR compared with MMR-proficient tumors, our findings demonstrate the critical function of JAK1 in immunological surveillance of dMMR cancer.

  Study phs002089

• University of Texas at Austin (UTA) Histone Modification and Gene Expression Profiling in 9 Primary Glioblastoma Multiforme, 2 Anaplastic Astrocytomas and Two Meningiomas

  The primary goal of this study was to collect and analyze genomic data from primary glioblastoma multiforme tumors. Our collaborators at St David's Medical Center (SDMC) obtained informed consent from patients undergoing surgery to remove a tumor in the brain. After consent was obtained, specimens were removed from the operating suite and flash frozen in liquid nitrogen. Tumors were analyzed if they were a grade III (anaplastic astrocytoma) or grade IV glioma (glioblastoma multiforme). Tumors were transported from SDMC to UT Austin, then weighed and homogenized. Chromatin immunoprecipitation was performed for 7 proteins in each tumor (histone modifications H3K4me3, H3K4me1, H3K9ac, H3K9me3, H3K27ac, H3K27me3, and the multifunctional insulator binding protein CTCF) and no-antibody input was also sequenced. An aliquot of tumor material was set aside for isolation of total RNA.

  Study phs001389

• Somatic L1 Retrotransposition in Colorectal Tumors

  The purpose of this study is to ascertain the locations of somatic LINE-1 retrotransposition events in human colon tumor samples by pooling multiple tumor samples from different patients and performing a targeted resequencing assay (Ewing and Kazazian, Genome Research 2010) to sequence the 3' flanking regions of all insertions in the pooled sample. The result is compared to the result of applying the same method to pooled normal samples from the same patients as were used in the pooled tumor sample and selecting sites that show an insertion in the tumor but not in the normaltissue and do not correspond to any known non-reference LINE-1 insertion allele. The selected sites are then validated by site-specific PCR and capillary sequencing to confirm that they represent LINE-1 insertions and to obtain breakpoint sequences.

  Study phs000536

• Genomic Predictors of Response to Immune Checkpoint Therapy

  Immune checkpoint therapies, including monoclonal antibodies to programmed cell death-1 (PD-1) and cytotoxic % lymphocyte associated protein-4 (CTLA-4), yield durable clinical responses across many tumor types, including metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, predictors of response to these therapies in RCC are still unknown. Genomic characterization of large clinical cohorts of patients treated with anti-CTLA-4 and anti-PD-1 agents in melanoma and NSCLC have suggested that high mutational burden, high neoantigen burden, and high expression of certain genes in pre-treatment tumors may be associated with patient response to these therapies. In this study, we sought to investigate genomic predictors of response to anti-PD1 therapy in metastatic RCC in two independent clinical cohorts using whole exome and whole transcriptome sequencing.

  Study phs001493

• Genomic Characterization CS-MATCH-0007 Arm B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing, RNA sequencing and if possible, whole-genome, methylation and miRNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH clinical trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with HER2- activating mutations are treated with Afatinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002028

• MP2PRT: Identification of Genetic Changes Associated with Relapse and/or Adaptive Resistance in Patients Registered as Favorable Histology Wilms Tumor on AREN03B2

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study, titled "Identification of Genetic Changes Associated with Relapse and/or Adaptive Resistance in Patients Registered as Favorable Histology Wilms Tumor on AREN03B2", performs genomic characterization (WGS 30X, Total RNAseq, miRNAseq) on a discovery set of 70 trio cases (normal tissue, tumor tissue at time of diagnosis, tumor tissue at time of relapse) from patients who relapsed with Favorable Histology Wilms Tumor. Prioritized findings from the discovery set will be validated using Targeted Sequencing in an independent validation set of 47 relapse samples.

  Study phs001965

• Sex Chromosome Aneuploidy Effects on Human Gene Expression

  Sex chromosome aneuploidy (SCA) syndromes are defined by the presence of a sex chromosome complement other than the typical XX for females and XY for males. SCAs are collectively common and increase risks for diverse immune, metabolic, and neuropsychiatric illnesses. Understanding genome-wide transcriptomic changes in SCAs is critical for clarifying the biological underpinnings of their clinical phenotypes. Assessments of sex chromosome dosage (SCD) effects on gene expression in humans have often been confined to the use of a few SCA subtypes (e.g., XO or XXY) - precluding analysis of the same SCD change in different contexts. Our study used RNA-seq data from lymphoblastoid cell lines in 197 individuals representing diverse SCA karyotypes (49 XX, 24 XXX, 39 XY, 39 XXY, 23 XXYY, 23 XYY) to assess expression changes for 25,075 genes in multiple pairwise SCD group comparisons. The paper reporting our findings has been cited below.

  Study phs003278

• Admixture Mapping of Staphylococcus aureus Bacteremia

  In this study, we used admixture mapping to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to Staphylococcus aureus bacteremia (SAB) in a sample of African Americans. A total of 565 adult African Americans were genotyped for admixture mapping. Cases were unique African American adult inpatients with monomicrobial SAB (N=390) and controls are age-matched adult African American inpatients with no current or past S. aureus infection (N=175). After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P = 4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB.

  Study phs001441

• Gabriella Miller Kids First Pediatric Research Program in Genetics at the Intersection of Childhood Cancer and Birth Defects

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Birth defects and childhood cancer share biological pathways that are important for cell growth and division. We propose that sequencing pediatric patients suffering both conditions will allow us to discover the underlying genes and in turn advance our understanding of the causes of these devastating diseases.

  Study phs001846

• Childhood Cancer Data Initiative (CCDI): OncoKids - NGS Panel for Pediatric Malignancies

  This study aimed to systematically collect clinical, registry and genomic data on pediatric cancer patients, and to contribute to the CCDI Pediatric Data Ecosystem. Clinical, treatment and outcome data on 1,039 pediatric cancer patients whose molecular profile was characterized on OncoKids gene panel at Children's Hospital Los Angeles was abstracted and harmonized for submission to the NCI’s Cancer Data Service. The OncoKids panel was designed to detect DNA mutations and amplification in almost 200 oncogenes and tumor suppressor genes, a limited number of pharmacogenomic targets and 1,700 disease-associated gene fusions at the RNA level. The panel encompasses the vast majority of FDA’s relevant pediatric molecular target list, as well as additional genes associated with ultra-rare pediatric tumors. The final data elements included DNA/RNA sequence data, OncoKids test results, clinical data on demographics, diagnosis, comorbidity and adverse events and treatment data.

  Study phs002518

• A Multimodal Atlas of Human Brain Cell Types

  "A multimodal atlas of human brain cell types" includes sample data targeting two cell types that show species differences between mouse and human. First, it includes a detailed transcriptomic, morphological, and electrophysiological characterization of cell types in layer 1 of human middle temporal gyrus, focusing primarily on different inhibitory cell types. This project also includes gene expression data collected from nuclei in layer 5 of human fronto-insula, with a goal of identifying transcriptomic signatures of Von Economo neurons. Control samples collected as part of the same experiment are also included in the data set. This study was conducted as part of a collaboration between the Allen Institute for Brain Science, the University of Szeged, and the J. Craig Venter Institute. Collaborators request that publications resulting from these data cite their original publication: Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type (PMID: 30150662).

  Study phs001791

• National Institutes of Health H3Africa African Collaborative Center for Microbiome and Genomics Research (ACCME)

  The African Collaborative Center for Microbiome and Genomics Research is a multi-institutional collaborative research project. The objectives of the project are to collaborate and implement high impact integrative epidemiology and genomics research into discovery of biomarkers associated with cervical carcinogenesis. Specifically ACCME links and leverages existing funded research and program activities at the collaborating institutions to study the interaction between vaginal microbiome, host genetic factors and molecular variants of Human Papilloma Virus (HPV) to determine correlates of viral persistence in the causal pathway of cervical cancer, a major cause of preventable mortality in Nigeria and other parts of sub-Saharan Africa. This research offers several opportunities to advance understanding of cervical carcinogenesis, viral oncogenesis, new biomarker discovery and risk stratification by genotype in a cohort of African women. Sponsorship: This project is sponsored by the National Institutes of Health (NIH)

  Study phs001945

• OncoArray: Oral and Pharynx Cancer

  Genetic factors play an important role in susceptibility to head and neck cancer and could also explain differences in response to treatment and outcome. The goal of this project is to investigate genetic variation involved in oral and oropharyngeal cancer susceptibility by performing the largest GWAS on these diseases, using a novel genotyping tool specifically designed for cancer studies by the OncoArray Network. This project encompasses data from approximately 6000 oral and pharynx cancer cases and 4000 controls derived from 12 epidemiological studies most of case-control design. The genotyping was centralized at the Center for Inherited Disease Research (CIDR), and the epidemiological data harmonization and analysis were completed at the International Agency for Research on Cancer (IARC). This study was supported by National Institute of Dental and Craniofacial Research (NIDCR) with direct funding to CIDR.

  Study phs001202

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Cleveland Clinic Cohort

  The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases. This study contains variant calls derived from the whole genome sequence data of an early-onset coronary artery disease case-control cohort collected by the Cleveland Clinic. Case status was assigned based on the presence of myocardial infarction, coronary artery stenosis greater than 70% in at least one coronary artery, and/or revascularization (coronary angioplasty with or without stent placement or coronary artery bypass grafting) at an early age. For these samples, "early age" is defined as men 60 years of age or younger and women 70 years of age or younger.

  Study phs001871

• Genomic Characterization CS-MATCH-0007 Arm Z1I

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1I is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with BRCA1, BRCA2 mutations are treated with AZD1775. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002058

• CIDR/NICHD Genetic Basis of Recessive Pediatric Brain Diseases - Group 2

  The purpose of this study is to identify new genetic causes of recessive forms of pediatric neurodevelopmental disorders (NDDs) including Cerebellar hypoplasia (CBH), Lissencephaly (LIS), Microcephaly (MIC), Corpus callosum hypoplasia (CCH), Pontocerebellar hypoplasia (PCH), Pontine tegemental cap dysplasia (PTCD), and Aicardi syndrome among many others. Using whole exome sequencing on one or two affected members per family, we are able to identify many pathogenic genes for these families. Using Human SNP Linkage Scans, which takes advantage of the Illumina HumanCore Array, and parametric linkage analysis software (Genehunter, Allegro, and others), we seek to identify pathogenic loci utilizing 60-70 families per year. Through the combination of parametric linkage analysis with exome sequencing and bioinformatics approaches, we will refine our search for superior sensitivity and accuracy when investigating candidate genes and identifying causative mutations for disease.

  Study phs001267

• A Single Cell Atlas of MMRd and MMRp Colorectal Cancer

  Immune responses to cancer vary across cancer types and patients. Colorectal cancer tumors with mismatch repair-deficiency (MMRd) show an elevated immune cell activity as compared to mismatch repair proficient (MMRp) tumors. To understand the immune response patterns in these two types of colorectal cancer, we transcriptionally profiled 371,223 tumor and adjacent normal cells from 28 MMRp and 34 MMRd patients. Unsupervised analysis identified 88 cell subsets, from 7 distinct cell clusters (that contain epithelial, malignant, stromal and immune cell lineages), and an associated compendium of 204 gene expression programs. Examination of these cell subsets and programs revealed extensive transcriptional and spatial remodeling of malignant, stromal and immune cells in MMRd and MMRp tumors. This dataset was generated as part of a published study (Pelka, Hofree, Chen, et al., Cell 2021 Sep 2;184(18):4734-4752; PMID: 34450029).

  Study phs002407

• Yale Center for Mendelian Genomics (YCMG)

  From 2012-2021, Yale University was home to one of four national centers created by the National Institutes of Health (NIH) to study the genetics of rare inherited diseases. Researchers at Yale University, University of Washington, the Broad Institute and a center operated jointly by Baylor University and Johns Hopkins University analyzed the genomes of thousands of patients who suffer from more than 6,000 rare Mendelian disorders affecting more than 25 million individuals in United States. The Centers for Mendelian Genomics (CMG) applied next-generation sequencing and computational approaches to discover the genes and variants that underlie Mendelian disorders. The discovery of new genes that cause Mendelian conditions expanded our understanding about their biology to facilitate their diagnosis, and potentially indicate new treatments. The CMG provided free exome sequencing and analysis to collaborating investigators for qualified phenotypes.

  Study phs000744

• The Epilepsy Phenome/Genome Project

  The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, international, multi-institutional, collaborative research project, sponsored by the National Institute of Neurological Disorders and Stroke, designed to understand the genes that cause common and rare epilepsies. The overall goal of EPGP is to collect detailed, high quality phenotypic (i.e., characteristics of individuals, from the molecular level to the whole person) information on persons with epilepsy and to compare the phenotypic information with genomic information. 27 clinical centers enrolled more than 4,100 participants of families with epilepsy. EPGP will provide a resource that may lead to many discoveries related to the diagnosis and treatment of epilepsy, including the eventual development of new therapies based on a better understanding of causes of the disorder. Documents and questionnaires that provide context to the variables and measurements available through the current study, are available for download from EPGP: Download EPGP Forms.

  Study phs000742

• Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA)

  Asthma is a complex disease where the interplay between genetic factors and environmental exposures influences susceptibility and disease prognosis. Asthmatics of African descent tend to have more severe asthma and more severe clinical symptoms than individuals of European ancestry. Advances in genetic and genomic technologies have revolutionized gene discovery for several complex diseases, but going to the next step in gene discovery for asthma among populations of African descent requires considering unique characteristics of this ethnic group, including adequate sample sizes and population stratification due to (European and African) admixture. Thus far, coverage of common genetic markers both in public databases and commercially available SNP chips has been inadequate to detect and measure genetic associations among African admixed populations. The aim of this study was therefore to catalog genetic diversity in populations of African descent, especially those whose ancestry reflects the African Diaspora in the Americas.

  Study phs001123

• Genomic Characterization CS-MATCH-0007 Arm Z1A

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1A is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with NRAS mutations are treated with Binimetinib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs001973

• Location and Function of NSun2-Mediated Cytosine-5 Methylation in RNA and its Effect on Translation

  Mutations in the cytosine-5 RNA methyltransferase NSun2 can cause neurodevelopmental disorders and symptoms commonly found in patients with Dubowitz-like syndrome. Some tRNAs are known to be methylated NSun2, however the occurrence of cytosine-5 methylation (m5C) in other RNA biotypes is still under debate. Location in RNA and function of m5C has not been studied yet. This study is aimed at identifying new m5C methylated RNA biotypes, as well as the location at specific structures or sequences and the ultimate biological function. The impact of the loss of NSun2-mediated methylation is also determined by comparing gene expression data with the global cytosine-5 RNA methylome in Dubowitz-like syndrome patients. We also use ribosomal profiling to assess the impact of the loss and rescue of Nsun2-mediated cytosine-5 RNA methylation on translation rates and ribosome occupancy.

  Study phs000645