12304 results for ""statistically+reactive"+taxa+in+microbial+community"

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• Microvascular Permeability, Inflammation, and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach

  The goal of the study is to identify novel molecular pathways involved in the etiology of endometriosis and to develop in vitro model systems to enable the study of the mechanisms regulating reproductive function. Using a physiomimetic modeling approach, primary tissue samples of the human endometrium derived from patients diagnosed with and without endometriosis and/or endometriotic diseases (e.g. adenomyosis) were used for secondary analysis using multi-omic systems biology analysis and to build tissue engineered models. We performed single cell RNA sequencing (scRNA-Seq, N=6)) to study the cellular and transcriptomic composition of the endometrial tissue microenvironment and proteomics (LC-MS/MS) to study protein-level signaling pathways and the matrisome of the native endometrium. Systems biology analysis of these datasets helped identified a putative dysregulated inflammatory signaling pathway in endometriosis patients compared to controls. Moreover, subsets from these scRNA-Seq and proteomic datasets were used to aid the design of a synthetic extracellular matrix hydrogel as an in vitro platform for the culture of endometrial cells. Tissue-engineered synthetic PEG hydrogel enables the simultaneous co-culture of endometrial epithelial organoids and stromal fibroblasts in a fully defined, 3D, and tunable environment. We demonstrated that the in vitro co-culture model recapitulates key phenotypic processes observed across the human menstrual cycle in response to sex hormone stimulation through both biochemical and transcriptomic (bulk RNA-sequencing) analysis. This model will enable future mechanistic studies that examine origins of endometriotic disease phenotypes. The transcriptomic data generated for this study including the scRNA-Seq data from primary human endometrial tissues and the bulk RNA-Seq datasets from the experimental co-culture models is available through dbGAP.

  Study phs003326

• Clinical and Molecular Features of Acquired Resistance to Immunotherapy in Non-Small Cell Lung Cancer

  PD-(L)1 blockade has been shown to promote durable responses in non-small cell lung cancer (NSCLC) patients and has been rapidly incorporated into the treatment regimens for many with advanced disease. Despite this, mechanisms of acquired resistance (AR) to PD-(L)1 have not been well understood. To address the clinical and molecular landscape of AR to PD-(L)1 blockade in NSCLC patients, a large clinical cohort of AR to PD-(L)1 blockade in lung cancer was examined. In conjunction, a systematic genomic and transcriptomic analysis in a subset of patients (n = 29) with available tissue samples was conducted. To investigate the molecular mechanisms of AR to PD-1 blockade from pre- and/or post-treatment tumors, microarray-based whole transcriptome expression data for 29 tumor samples, and whole exome sequencing (WES) data from 34 tumor samples was generated from this subset. Microarray data was uploaded to the Gene Expression Omnibus (GEO) database. Most AR tumors showed retained or increased inflammatory characteristics with significant upregulation of IFNγ which was suggestive of persistent albeit insufficient anti-tumor immune response. This finding expounds upon the prior pre-clinical and translational data supporting the intricate role of IFNγ in sensitivity and resistance to immunotherapy. Whereas initial IFNγ exposure may be fundamental to T cell activation (a hallmark of immune response), persistent IFNγ related effects and upregulation may potentially signal immune dysfunction and IFNγ insensitivity in contrast. The inflammatory phenotypes identified have implications for future rational development of new immunotherapy strategies for patients with AR.

  Study phs002834

• The phase II Neo-Pembro trial: neoadjuvant pembrolizumab in stage IV high-grade serous ovarian cancer

  While immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, their efficacy in high-grade serous ovarian cancer (HGSOC) remains limited. Nevertheless, some patients achieve lasting responses, emphasizing the need to understand how the tumor microenvironment and molecular characteristics influence ICI response. We hypothesized higher efficacy of ICI when used in the neoadjuvant setting and preceded by induction chemotherapy. The phase 2 Neo-Pembro study (NCT03126812) included 33 untreated patients with stage IV HGSOC who were planned for 6 cycles of carboplatin-paclitaxel and interval cytoreductive surgery. Pembrolizumab (pembro) was added from cycle two and continued for one year. The primary objective was to assess intratumoral immune activation, through multiplexed immunofluorescence and immune-related gene expression. Our data provide evidence of immune activation, characterized by an increase in CD3+, CD8+, CD8+/FOXP3+ ratio, and TNF-α and interferon-γ signaling, and was most evident in major pathologic responders, which were 9/33 patients (27%, 95%CI 14-46) at time of surgery. Pathologic response was strongly associated with overall survival. At a median follow-up of 52.8 months, 8/9 major responders were alive, including 6 patients without recurrence, and 4 of 24 minor responders were alive, including one patient without recurrence. PD-L1 expression and homologous recombination deficiency were predictive of major response and may serve as potential biomarkers, warranting further exploration. In a post-hoc comparison, major responders treated with pembro had significantly better overall survival than major responders in a historic cohort treated without pembro. Our data indicate that immune activation was stronger in the subset of major pathologic responders and these patients may derive long-term survival benefits from the addition of neoadjuvant pembro.

  Study EGAS50000000781

• Clonal Lineage Tracing of Primary Human Cortical Progenitors, Cell Type Profiles in the Brain Vasculature and Genotyping Data for 22q11DS and Control iPS Lines

  We sought to characterize the cell types produced by individual human cortical progenitors and describe their lineage relationships. We labeled individual human cortical cells with a massively complex lentivirus library encoding a GFP reporter gene and a molecular barcode that could be captured by standard 3' scRNA-seq methodologies. We then cultured the labeled human cells for 6 weeks in either a 1) mouse cortical astrocyte co-culture system or 2) in the mouse cortex as a xenograft. In a separate experiment, we maintained human cortical tissue slices in organotypic slice culture for 12 days. GFP+ cells were then isolated by FACS and then captured on the 10x chromium scRNA-seq platform. An additional sample was labeled by lentivirus and briefly cultured for 3 days prior to being mixed with mouse 3T3 cells in order to perform a cell mixing experiment ("barnyard") to benchmark our methodologies. We found that human individual cortical progenitors gave rise to both excitatory and inhibitory neurons as well as glia.We also sought to characterize the adult brain vasculature in both vascular malformations and non-malformed tissue. We use the 10x chromium scRNA-seq platform across 10 individuals (5 control and 5 arteriovenous malformations). We find broad disregulation across multiple cell types including the immune cells and find a specific monocyte subtype to contribute to a rupture phenotype. We also find a novel population of fibromyocytes in both conditions.Finally, we confirmed the genotype status of iPS lines that were derived from either karyotypically normal control individuals or from DiGeorge Syndrome patients carrying the 22q11.2 deletion using the Illumina Infinium Global Screening Array v3.0.

  Study phs002624

• Repeat expansions with small TTTCA insertions in MARCHF6 cause Familial Adult Myoclonus without Epilepsy

  Familial Adult Myoclonic Epilepsy (FAME) is a rare autosomal dominant disorder characterized by cortical tremulous myoclonus and generalized tonic clonic (GTCS) or myoclonic seizures. Intrafamilial variability regarding the prevalence of seizure has been reported. Despite apparent genetic heterogeneity, FAME is caused by the same TTTTA/TTTCA pentanucleotide repeat expansion in introns of seven different genes with no common function. Expansions containing only TTTTA repeats are benign, and only expansions including a TTTCA expansion insertion, which can be located 3' to the TTTTA expansion or in the middle of the TTTTA repeats, are pathogenic. We aimed to identify the underlying genetic cause of dominant cortical myoclonus without GTCS in two unrelated families. We used a combination of repeat-primed PCR, long-range PCR and nanopore sequencing to detect and characterize expansions at known FAME loci. We report a novel configuration of the FAME3 repeat expansion in MARCHF6 segregating with cortical myoclonus without epilepsy GTCS in both families. This expansion predominantly comprises elongated TTTTA repeats, ranging from 388 to 454 repeats, with the presence of only 5-11 TTTCA repeats at its 3' terminus (i.e., 5’-(TTTTA)~388-454(TTTCA)5-11-3’). This configuration exhibits greater stability upon meiotic transmission but somatic variability in TTTCA repeat number was detected at low level in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset. This study shows that as little as five TTTCA juxtaposed with expanded TTTTA expansions is sufficient to cause cortical myoclonus without GTCS. This finding has implications regarding possible pathophysiological mechanisms leading to FAME.

  Study EGAS50000000570

• CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory

  Foxp3-expressing CD25+CD4+ regulatory T cells (Tregs) are abundantly infiltrating into tumor tissues, hindering effective anti-tumor immunity. Here, assuming that such tumor Tregs were clonally expanding by recognizing tumor-associated antigens, we attempted to characterize them by their gene expression profiling and T-cell receptor (TCR) clonotyping at the single-cell level. We found that they predominantly expressed the chemokine receptor CCR8: ~40% of tumor Tregs, less than 10% of Tregs in other tissues, and few tumor-infiltrating conventional T cells expressed CCR8 in mice and humans. CCR8+ tumor Tregs were phenotypically highly differentiated and functionally stable. One injection of anti-CCR8 mAb with high antibody-dependent cellular cytotoxic activity was indeed able to specifically deplete clonally expanded tumor Tregs and thereby eradicate established tumors in mice. The depletion predominantly expanded tumor-infiltrating CD8+ effector T cells, which were different in activated or exhausted patterns from those seen after immune checkpoint blockade by anti-PD-1 mAb. The treatment also evoked potent secondary immune responses against the same tumor cell line inoculated several months after tumor eradication, indicating that the anti-CCR8-induced memory-type tumor-reactive effector T cells were, once induced, resistant to recovered Treg suppression. In contrast to such evocation of potent tumor immunity, anti-CCR8 treatment scarcely elicited discernable autoimmunity in mice, contrasting with a similar treatment for systemic whole Treg depletion, which induced histologically and serologically evident autoimmunity. Thus, temporary and specific depletion of clonally expanded Tregs in tumor tissues by cell-depleting anti-CCR8 mAb is sufficient to evoke potent tumor immunity with long-lasting memory and without serious autoimmunity.

  Study JGAS000312

• Biallelic variants in the non-protein coding minor spliceosome components RNU6ATAC and RNU6ATAC cause syndromic monogenic autoimmune diabetes

  Non-protein coding genes are emerging as critical contributors to the aetiology of rare diseases, providing key insights into human biology and uncovering novel disease mechanisms. We identified 7 individuals from 4 families with early-onset diabetes (diagnosed <5 years) and immune dysregulatory features caused by biallelic variants in RNU6ATAC. RNU6ATAC encodes a small nuclear RNA (snRNA) acting as a catalytic component of the minor spliceosome, a protein-RNA complex mediating splicing of ~700 genes containing U12/minor-type introns. Variant screening of the other 64 minor spliceosome genes in 276 infants with diabetes identified 12 unrelated individuals with biallelic disease-causing variants in RNU4ATAC. Biallelic pathogenic RNU4ATAC variants are known to cause a variable spectrum of clinical features, which until now did not include diabetes. Clinically, 12/19 RNU6ATAC/RNU4ATAC patients had additional immune dysregulatory features, and 50% of patients tested were islet-autoantibody positive, strongly supporting an autoimmune aetiology for their diabetes. RNA-seq in 3 individuals with biallelic RNU6ATAC variants showed a pattern of intron retention in U12 intron-containing genes similar to that seen in RNU4ATAC-individuals (n=3), supporting a shared disease mechanism. Analysis of patients’ transcriptomic, methylation and immune data revealed impaired B cell development and maturation. We conclude that biallelic RNU6ATAC variants cause a novel syndrome of early-onset autoimmune diabetes and immune dysregulation. We further show that infancy-onset diabetes is a previously unrecognised feature of RNU4ATACopathy. Our work highlights the important role of two snRNAs critical to minor spliceosome function in immune system regulation, providing novel insights into the pathogenesis of autoimmune diabetes.

  Study EGAS50000001565

• Molecular subtypes of pancreatic neuroendocrine tumors mutated in MEN1/DAXX/ ATRX explain biological variability

  Pancreatic Neuroendocrine Tumors (PanNETs) most probably arise from the islets of Langerhans, although direct evidence is still lacking. About 40% of non-functioning (NF) PanNETs harbour mutations in MEN1, often in conjunction with alterations in DAXX/ATRX. Despite the homogeneous genetic background, the ADM (mutation in DAXX/ATRX and MEN1) group is heterogeneous regarding molecular features and response to treatment. To explore the molecular and clinical heterogeneity within this group, we integrated transcriptomic and DNA methylation data from 36 and 93 samples, respectively. Using a multi-omic approach we described a two-level hierarchy separating PanNET subtypes mutated in MEN1, DAXX and ATRX. First, DNA methylation discriminates ADM-PanNET from PanNET mutated in MEN1 only (α-like). Compared to α-like, all ADM tumors exhibit DNA methylation changes at enhancer and lowly methylated regions as well as at peri-centromeric and telomeric regions, associated with alternative lengthening of telomeres, increased chromosomal instability, and enhanced proliferative capacity. At a second level, transcriptomic analysis revealed three distinct ADM subtypes: ADM hypoxic, ADM NST (No Special Type), and ADM immunosuppressive. The ADM hypoxic subtype is characterized by strong hypoxia signature, likely regulated epigenetically. The ADM NST subtype appears to be primarily driven by epigenetic changes that promote proliferation. The ADM immunosuppressive is highly enriched in immune component and strong metastasis-like signature. While all the three subtypes are highly associated with liver metastasis formation and invasion, the ADM immunosuppressive are significantly smaller (&lt;2.5 cm p.value=0.023) despite displaying aggressive molecular features. By defining these three novel ADM subtypes, our study provides a refined framework for understanding PanNET heterogeneity. This classification underscores potential diagnostic markers and highlights distinct biological vulnerabilities that may inform the development of subtype-tailored therapeutic strategies.

  Study EGAS00001008272

• Genesis of Two Most Prevalent Variants Causing Combined Pituitary Hormone Deficiency in 21 Populations

  Two variants (c.[301_302delAG];[301_302delAG] and c.[150delA];[150delA]) in the PROP1 gene are the most common genetic causes of recessively inherited combined pituitary hormones deficiency (CPHD). Our objective was to analyze in detail the origin of the two most prevalent variants. In the multicentric study were included 237 patients with CPHD and their 15 relatives carrying c.[301_302delAG];[301_302delAG] or c.[150delA];[150delA] or c.[301_302delAG];[ 150delA]. They originated from 21 different countries worldwide. We genotyped 21 single nucleotide variant markers flanking the 9.6Mb region around the PROP1 gene that are not in mutual linkage disequilibrium in the general populations - a finding of a common haplotype would be indicative of ancestral origin of the variant. Haplotypes were reconstructed by Phase and Haploview software, and the variant age was estimated using an allelic association method. We demonstrated ancestral origin of both variants: c.[301_302delAG] was carried on 0.2Mb-long haplotype in a majority of European patients arising approximately 101 generations ago (confidence interval 90.1-116.4). Patients from the Iberian Peninsula displayed a different haplotype which was estimated to have emerged 23.3 (20.1-29.1) generations ago. Subsequently, the data indicated that both haplotypes were transmitted to Latin American patients approximately 13.8 (12.2-17.0) and 16.4 (14.4-20.1) generations ago, respectively. The c.[150delA] variant that was carried on a haplotype spanning about 0.3Mb was estimated to appear 43.7 (38.4-52.7) generations ago. We present strong evidence that the most frequent variants in the PROP1 gene are not a consequence of variant hot-spots as previously assumed, but are founder variants.

  Study EGAS00001001165

• Induced Pluripotent Cells Derived from Differentiated Rod Photoreceptors Undergo Efficient Retinogenesis in Three-Dimensional Cultures

  "Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are used to study lineage-specific differentiation in culture. We developed a standardized quantitative protocol called STEM-RET to compare eye field specification, optic cup formation, and retinal differentiation across stem cell populations. We reprogrammed individual rod photoreceptors into iPSCs by inducible expression of Oct3/4, Klf4, Sox2, and Myc. We also developed ESC lines from rods by somatic cell nuclear transfer. Using the STEM-RET protocol, we compared the abilities of ESCs, fibroblast-derived iPSCs (f-iPSCs), rod photoreceptor-derived iPSCs (r-iPSCs), and rod photoreceptorderived ESCs to form retinae using STEM-RET. r-iPSCs were the most efficient at producing differentiated retina. Retinae derived from f-iPSCs lacked an inner nuclear layer (INL) and had a concomitant reduction in amacrine cells and other INL cell populations. The INL-specific LIM homeobox gene, Lhx9, was hypermethylated in fiPSCs and concomitantly downregulated in retinae derived from those stem cells. ChIP-seq analysis for H3K36me3, H3K4me1, H3K4me3, H3K9/14Ac, H3K27me3, H3K9me3, CTCF and 5 hydroxymethyl cytosine showed that the major difference between the r-iPSCs and the f-iPSCs were in the genes marked by the CTCF insulator protein. Importantly, CTCF binding enrichment at rod photoreceptor specific genes was at least 10-fold higher in r-iPSCs relative to f-iPSCs. Taken together, our data suggest that both inhibitory and permissive epigenetic marks important for retinal development can be retained in iPSCs and such marks can be exploited to select the most favorable stem cell population to study retinal development or produce photoreceptor precursors for cell transplantation."

  Study EGAS00001001288

• Tumor-derived cell lines as pharmacogenomic models to predict therapeutic vulnerabilities in hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. We performed multi-omic analysis including whole-exome, RNA and miRNA sequencing and quantification of 126 proteins in a series 34 LCCL coupled with a screening of 29 anti-cancer agents. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular "proliferation class" of HCC. Genomic alterations of the RAS-MAPK pathway correlated with trametinib sensitivity that was more potent than FGFR4 inhibitors in tumor cells depending on the FGF19/FGFR4 pathway. Moreover, we showed that FGF19 amplification was only functional in tumor cells that retained a hepatocyte differentiation program with expression of FGFR4, KLB and NR1H4 highlighting the complex interplay between the genomic and transcriptomic context in drug response. We also identified drugs/combination that could target efficiently the transcriptomic "progenitor subclass of HCC", as well as specific genetic contexts such as inactivating mutations in TSC1/TSC2 and TP53 associated with higher sensitivity to the mTOR inhibitor rapamycin and the AURKA inhibitor alisertib, respectively. LCCL represent relevant preclinical models for drug-biomarker discovery in HCC and enabled to identify molecular contexts linked with particular therapeutic vulnerabilities that may be useful to stratify patients in future clinical trials

  Study EGAS00001003536

• Tumor-specific expression of let-7i and miR-192 is associated with resistance to cisplatin-based chemoradiotherapy in patients with larynx and hypopharynx cancer

  Background: The majority of patients with locally advanced larynx or hypopharynx squamous cell carcinoma are treated with organ preserving chemoradiotherapy (CRT). Clinical outcome following CRT varies greatly. We hypothesized tumor microRNA (miRNA) expression is predictive for outcome following CRT. Methods: Next-generation sequencing (NGS) miRNA profiling was performed on 37 formalin fixed paraffin embedded (FFPE) tumor samples. Patients with a recurrence free survival (RFS) of less than 2 years (“poor outcome”) and patients without recurrence within 2 years (“good outcome”) were compared by differential expression analysis. Tumor-specific miRNAs were selected based on normal mucosa miRNA expression data from The Cancer Genome Atlas database. A model was constructed to predict outcome using group-regularized penalized logistic ridge regression. Candidate miRNAs were validated in the initial sample set by RT-qPCR as well as in 46 additional tumor samples.Results: 1,938 known mature miRNAs were detected. Thirteen miRNAs were differentially expressed (p&lt;0.05, FDR&lt;0.1) according to outcome group. Initial class prediction in the NGS cohort (n=37) resulted in a model combining five miRNAs and disease stage, able to predict CRT outcome with an area under the curve (AUC) of 0.82. In the RT-qPCR cohort (n=83), 25 patients (30%) experienced early recurrence (median RFS 8 months; median follow-up 42 months). Class prediction resulted in a model combining let-7i-5p and miR-192-5p and disease stage, able to discriminate with an AUC of 0.80 patients with good versus poor clinical outcome.Conclusion: The combined miRNA expression and disease stage prediction model is superior to using either factor alone. ¬¬¬This study indicates NGS miRNA profiling using FFPE specimens is feasible, resulting in clinically relevant biomarkers.

  Study EGAS00001004001

• Exploration of coding and non-coding variants in cancer using GenomePaint.

  GenomePaint (https://proteinpaint.stjude.org/genomepaint) is a dynamic visualization platform for whole-genome, whole-exome, transcriptome, and epigenomic data, featuring a novel design that captures the inter-relatedness between DNA variations and RNA expression. Regulatory non-coding variants can be inspected and discovered along with coding variants, and their functional impact further explored by examining 3D genome and/or ChIP-seq data generated from cancer cell lines. Further, GenomePaint correlates mutation and expression patterns with patient outcomes, and can display external data such as adult cancer datasets and user-provided custom tracks. We used GenomePaint to analyze multi-omics data from 3,652 pediatric cancers representing 16 histotypes, and demonstrate the visualization features through examples, including two that led to new insights into oncogenic mechanisms in pediatric cancer. The first is the discovery of a new class of pathogenic recurrent variants that cause aberrant splicing, disrupting the RING domain of CREBBP, a driver gene frequently mutated in relapsed pediatric leukemia. The second is the cis-activation of the MYC oncogene in a subset of B-lineage acute lymphoblastic leukemia (B-ALL) via duplication of the NOTCH1-MYC enhancer (N-ME), previously discovered only in T-lineage ALL. The regulatory impact of N-ME enhancer amplification was initially confirmed by allelic imbalance in published gene expression and ChIP-seq data and verified by additional Capture-C and fluorescence in situ hybridization data generated by follow-up experiments. These examples demonstrate the power of GenomePaint in enabling not only data visualization but also integrative genomic analysis that can lead to novel biological insight for follow-up experimental validation.

  Study EGAS00001004669

• Long-term temporal stability of peripheral blood DNA methylation alterations in patients with inflammatory bowel disease.

  Introduction There is great current interest in the potential application of DNA methylation alterations in peripheral blood as biomarkers of susceptibility, progression, and treatment response in inflammatory bowel disease (IBD). To date, the intra-individual stability of peripheral blood leukocyte (PBL) methylation in IBD patients, a key consideration in biomarker development, has not been characterised. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array. Methods We followed a cohort of 46 adult IBD patients (36 Crohn’s disease (CD), 10 ulcerative colitis (UC), median age 44 (IQR: 27-56), 50% female) that received standard care without any intervention at the Amsterdam UMC. Paired PBL samples were collected at two time points with a median 7 (range: 2-9) years in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively. Results Around 60% of all CpG loci on the EPIC array presented poor (ICC &lt;0.50); 119,388 (≈14%) and 41,274 (≈5%) showed good (ICC ≥0.75) or excellent (ICC ≥0.90) intra-individual stability. Functional over-representation analyses of the stable methylated CpGs implicated genes involved in cell-cell signaling, adhesion and neurogenesis. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated good stability (ICC ≥0.75) over time, where we observed a marked stability of CpG loci associated to the HLA genes. Conclusion Our data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation.

  Study EGAS00001006501

• Converging and evolving immuno-genomic routes towards immune escape in breast cancer

  This study explores the evolution of tumor and blood immune microenvironment and related mechanisms that shape breast cancer progression, culminating in a heterogeneous lethal cancer.

  Study EGAS00001004956

• Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

  Targeted cfDNA and WBC sequencing data from patients profiled in the study "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer". Note that 'Exome sequencing' is listed under Dataset Type since there is no option for targeted panel sequencing.

  Dataset EGAD50000000303

• CIDR: Discovery, Biology, and Risk of Inherited Variants in Glioma

  This is a gliogene brain tumor family study. This study includes glioma cases with a family history of glioma in a first, second, or third degree relative.&nbsp;

  Study phs002250

• LRS - episignature samples

  This dataset contains 22 long-read WGS fastq.gz files sequenced ONT PromethION. In total the dataset includes 20 individuals, for all of them sequencing starting from blood was performed, and for one of the samples sequencing from urine and from the buccal swab was also included. In all the samples methylation calls are included in the fastq file.

  Dataset EGAD50000001000

• Whole genome sequence analysis in patients with primary central nervous system lymphomas

  We performed target amplicon sequencing analysis in 28 patients with primary central nervous system lymphomas using target capture technology (NGS) on Cancer Panel to explore molecular targets.

  Study JGAS000258

• GWAS of tuberculosis in Russia

  Genome-wide association study of cases of tuberculosis from St Petersburg and Samara, in Russia, compared to healthy controls from the same two cities. Genotype data from Affy6 array.

  Study EGAS00001001090

• Whole-genome DNA methylation profiling of CD14+ monocytes reveals disease status and activity differences in Crohn’s disease patients

  Identifying differences in CD14+ monocyte methylation between CD and non-CD patients, as well as between CD-active and CD-remissive patients.

  Study EGAS00001004221

• Germline DNMT3A mutation in mother-son pair with AML

  A mother/son pair with adult onset diploid AML were evaluated and found to have a dominant negative germline mutation in DNMT3A that is associated with global hypomethylation

  Study EGAS00001002940

• Cabozantinib Response in ETV6-NTRK3 G623R Positive Carcinoma HIPO-021

  We report a case of marked response to cabozantinib in a secondary entrectinib-resistant tumor harboring the ETV6-NTRK3 fusion with a G623R solvent-front mutation.

  Study EGAS00001004494

• RNA sequencing of Human Organoid Lines

  The study will use RNA sequencing to aid in benchmarking different culture conditions in a set of genetically annotated human organoid lines. The data will be used to assess whether there are any clonal differences introduced when culturing these lines in different conditions.

  Dataset EGAD00001007971

• WES_localized non-small cell lung cancer (540 samples)_MDACC

  Whole exome sequencing of tumors and paired adjacent uninvolved tissues from 222 early stage NSCLC patients, in order to identify genomic drivers present in early-stage non-small cell lung cancer and determine the overall tumor mutational burden in early-stage non-small cell lung cancer.

  Dataset EGAD00001005956

• Cohort of NGS lymphoma samples used as control

  Control cohort of lymphoma samples sequenced with a hybrid capture panel designed to be able to detect translocations and mutations in lymphoma samples. used in the paper "Robust detection of translocations in lymphoma FFPE samples using Targeted Locus Capture-based sequencing"

  Dataset EGAD00001007711

• HiC-sequencing in human monocyte differentiation

  This dataset consists of in situ HiC-seq data from human monocytes, monocyte-derived dendritic cells as well as monocyte-derived cells that were subjected to siRNA treatment targeting CTCF or RAD21. In total, the data set includes 42 samples.

  Dataset EGAD00001007955

• GATCI whole genome sequence data

  Sequence data in fastq format was aligned to the GRCh38 reference genome with BWA-MEM. Aligned sequence was preprocessed with GATK for Indel Realignment and Base Quality Score Recalibration. Duplicates were marked with Picard Mark Duplicates. Aligned sequence is in bam format. Details of the alignment can be found in the bam header

  Dataset EGAD00001005914

• Non-coding mutations reveal cancer driver cistromes in luminal breast cancer

  A dataset of ER+PR+ breast tumor samples that were analyzed in order to identify mutation enrichment in cis-regulatory elements and cistrome. The repository includes sequencing data from 88 patients. 26/88 were sequenced using ATAC-seq

  Dataset EGAD00001007650

• GIS-LUNGTCR1-2016_VAL-FASTQ

  This dataset contains FASTQ files of targeted Amplicon deep-sequencing data, for validation of the mutations found in WES. There are 16 patients and 95 samples in total, including 16 controls and 79 tumors. 140 fastq in total, multiple runs for some of the samples. Please refer to the sample-ID from filename for merging.

  Dataset EGAD00001001981

• 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.

  Study EGAS00001000023

• Single Cell Analysis of Pulmonary Fibrosis

  Pulmonary fibrosis is a heterogenous syndrome in which fibrotic scar replaces normal lung tissue. We performed massively parallel single-cell RNA-Seq on lung tissue from eight lung transplant donors and eight patients with pulmonary fibrosis. Combined with in situ RNA hybridization, with amplification, these data provide a molecular atlas of disease pathobiology. We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to non-overlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. Analysis of a cryobiopsy specimen from a patient with early disease supports the clinical application of single-cell RNA-Seq to develop personalized approaches to therapy.

  Study phs001750

• Genomic sequencing of Pediatric Rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood accounting for approximately 350 newly diagnosed cases yearly in the United States. With the development of multimodal chemotherapy regimens, relapse-free survival rates have improved to 70-80% in patients with localized disease albeit with significant toxicity. Unfortunately, despite aggressive treatment, patients with metastatic or recurrent disease continue to suffer from high mortality. Further characterization of the genetic events underlying this tumor type is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. In a collaborative effort between the National Cancer Institute, the Children's Oncology Group, and the Broad Institute, we use a combination of whole-genome and whole-exome sequencing to characterize the landscape of somatic alterations in 147 tumor/normal pairs.

  Study phs000720

• DNA Methylation Analysis of Peripheral Blood Cells from Siblings Discordant for ASD

  Autism is a common disorder whose causes are poorly understood. Both genetic and environmental influences are thought to act together causing autism. Epigenetics is an area that bridges genetic and environmental influencing and commonly is studied by examining dynamic methylation changes to the DNA. We have screened a total of 78 autistic boys and their fathers by this method in 807 genes and find 116 methylation changes that together can correctly identify nearly 80% of the affected boys from their fathers. We propose to confirm these exciting data in a much larger set of genes in 1,200 autistic boys and their families, including unaffected brothers. These data not only could provide new insight into the causes of autism but could also result in a screening test for autism.

  Study phs000619

• GWAS for IgA Nephropathy

  IgA nephropathy (IgAN) is a common form of immune-mediated glomerulonephritis characterized by glomerular deposition of IgA-containing immune complexes and manifesting with hematuria, proteinuria, and often kidney failure. This dataset is from a genome-wide association study (GWAS) designed to identify novel genetic risk loci for IgAN. In this dataset, seven cohorts were genotyped by Illumina Multi-Ethnic Global Array, consisting of 3,337 IgAN cases and 2,177 healthy controls of European and East Asian ancestries. Three of the provided cohorts were genotyped by Illumina HumanImmuno Chip, which are composed of 2007 cases of IgAN of European ancestry. These cohorts were used in the GWAS meta-analysis, as described in the manuscript entitled "GWAS defines pathogenic signaling pathways and prioritizes drug targets for IgA nephropathy" (Nature Genetics 2022, in press).

  Study phs000431

• Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

  Gastric cancers are cancers of the stomach. Hereditary cancers are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. Bulk RNA sequencing (RNA-seq) of signet ring cells (SRCs) and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from hereditary diffuse gastric cancer (HDGC) patients (Clinicaltrials.gov ID: NCT03030404). Twenty patients (6 male, 14 female) with confirmed HDGC were identified. Analysis of differentially expressed genes (DEGs) demonstrated upregulation of certain individual epithelial&#8211;mesenchymal transition (EMT) and proliferation genes. SRC regions had significant enrichment in pathways involved in T cell signaling. CIBERSORTx predicted significant increases in the presence of regulatory T cells (Tregs) specific to SRC regions.

  Study phs003422

• Smoking-dependent expression alterations in nasal epithelium reveal immune impairment linked to germline variation and lung cancer risk.

  Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to lifestyle risk in the form of cigarette smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, often many years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk are unclear. CT screening of current and former smokers has been shown to reduce lung cancer mortality by up to 26%. To examine whether clinical risk stratification can be improved upon by the addition of genetic data, and to explore the mechanisms of the persisting risk in former smokers, we have analyzed transcriptomic data from accessible airway tissues of 487 subjects. We developed a model to assess smoking associated gene expression changes and their reversibility after smoking is stopped, in both healthy subjects and clinic patients. We find persistent smoking associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune and interferon related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. Our results provide initial evidence for germline-mediated personalised smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality.

  Dac EGAC50000000169

• The characterization of gene expression pattern of anticancer agent-resistant cancer stem cells using RNA sequencing analysis.

  Slow cycling cancer stem cells persist and contribute to tumor regrowth after chemotherapy.To investigate this mechanism, we developed stemness- and cell cycle-visualized colon cancer organoids from patient tissues, and perfomed comparative transcriptome analysis using sorted rapid cycling stem cells (LGR5+p27-) and slow cycling stem cells (LGR5+p27+). In addition, we analyzed the changes in the gene expression patterns in the slow cycling stem cells and all of tumor cells after chemotherapy (camptothecin) treatment. Gene ontology analysis and gene set enrichment analysis using these transcriptome data revealed cell adhesion signal and YAP siganling pathway were important to maintain the dormancy and resume propagation after chemotherapy. In each experiments, total RNA was extracted from organoids and sequenced with HiSeq X Ten (Illumina).

  Study JGAS000350

• Evolutionary Origins of Recurrent Pancreatic Cancer

  Surgery is the only curative option for patients with Stage I/II pancreatic cancer, nonetheless most patients will recur after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer we performed whole exome or targeted sequencing of 10 resected primary cancers and their matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease develops from a monophyletic or polyphyletic origin, and this distinction has potential clinical relevance. In all patients, treatment induced genetic bottlenecks led to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In one patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings strongly advocate for routine post-treatment sampling in the management of recurrent pancreatic cancer.

  Study EGAS00001004097

• Multi-omics analysis of serial samples from metastatic TNBC patients on PARP inhibitor monotherapy provide insight into rational PARP inhibitor therapy combinations

  In a pilot study, we evaluated the safety and efficacy of olaparib/durvalumab combination treatment in mTNBC patients and the feasibility of real-time deep analysis of serial tumor samples from triple negative breast cancer patients to identify mechanisms of resistance and treatment opportunities. This study used the SMMART analytic platform at OHSU KCI and incorporated comprehensive multi-omic analysis of serial liquid and tumor biopsies. Deep analysis of longitudinal biopsies combined with a robust computational biology pipeline identified multiple PARPi-induced changes in immune activation, DNA damage checkpoint activation, apoptosis and signaling pathways including RTK, PI3K-AKT and RAS-MAPK. These emergent tumor and immune state changes could act as biomarker targets to be used in selecting patient specific combination therapies.

  Study EGAS00001005479

• Two lung cancer cell lines with EGFR mutations, PC-9 and KHM-3S, were either treated with Tarceva for 24 hours or left untreated. The gene expression profiles were examined by RNAseq, and the genome wide binding profiles of total STAT3 and pSTAT3 were characterized by ChIPseq.

  Lung cancers harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as Tarceva. However, nearly all patients show relapse within 1 year after initial treatment. To investigate the early signaling switches that are involved in the formation of drug resistance, and the role of STAT3 in the early signaling switches involved in the formation of drug resistance, we have treated two lung cancer cell lines with EGFR mutations, PC-9 and KMH-3S, with Tarceva for 24hours. The RNA samples with and without treatment were collected in triplicate for RNAseq experiment.The total STAT3 and pSTAT3 chromatinIP were done on samples with and without treatment for ChIPseq.

  Study EGAS00001000793

• Sequencing of Infant high grade gliomas

  Infant high grade gliomas appear distinct from their counterparts in older children, indicating that grading may not accurately reflect the biology of these tumours. We have collected 228 cases under 4 years of age, and carried out histological review, methylation profiling (217), custom panel (15) and genome (20)/exome (12) sequencing. After excluding cases representing other established entities or subgroups, we identified 120 cases to be part of an intrinsic spectrum of disease in the infant population. These included those with targetable MAP-kinase alterations, and a large proportion of remaining cases to harbour gene fusions targeting ALK, NTRK1/2/3, ROS1 and MET as their driving alterations, with evidence of efficacy of targeted agents in the clinic. Infant gliomas require a change in diagnostic practise and management.

  Study EGAS00001003532

• The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas

  Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the central nervous system TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to the impaired circulation of cerebrospinal fluid resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. Here, we performed RNA-Seq and small RNA-Seq on SEGAs (n=19) and periventricular controls (n=8) to gain a better understanding of the underlying molecular basis of SEGAs, so that novel treatment targets could be identified.

  Study EGAS00001003787

• Single-cell multi-omics of relapse/refractory multiple myeloma patients (Hipo K08K/H067/K43R)

  Therapy resistance in cancers is ingrained in complex clonal dynamics. While the major clonal population in a tumour might respond well to the employed intervention, minor clones will eventually mutate, consequently acquiring a selective advantage and drug resistance. Hence, to improve cancer therapy, it is crucial to understand the mechanisms behind clonal evolution. Here, we applied single-cell transcriptomics and epigenomics, as well as whole-genome sequencing to 15 patients with relapsed/refractory multiple myeloma (RRMM). By profiling longitudinal samples throughout varying treatment regimens, we were able to interrogate patterns of evolution across patients. In particular, by defining clones based on copy number aberrations (CNAs), we found evidence for the majority of clones being diminished but not fully eradicated during treatment.

  Study EGAS00001006538

• The Iberian Roma genetic variant server

  The Roma are the most numerous ethnic minority in Europe. The Iberian Roma arrived in the Iberian Peninsula five centuries ago and still today, they keep a strong group identity. Demographic and cultural reasons lie behind a high rate of Mendelian disease often related to founder variants. We have analysed exome data from 119 Iberian Roma individuals collected from 2018 to 2020. A database of variant frequency has been implemented (IRPVS) and made available online. We have analysed the carrier rate of founder private alleles as well as pathogenic variants present in the general population. Significant enrichment in structural variants involving gene clusters related to keratinization and epidermal growth suggest that evolutive mechanisms have developed towards climate and environmental adaptation. IRPVS can be accessed at http://irpvs.clinbioinfosspa.es/

  Study EGAS00001006758

• Correction of a Factor VIII genomic inversion with designer recombinases

  Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in 12% correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.

  Study EGAS00001005496

• A panel of reference haplotypes for imputing complement component 4 (C4) gene structural variation

  Neuropsychiatric and autoimmune disorders have substantial epidemiological correlations (Benros et al., JAMA Psychiatry 2013, PMID: 23760347) and broad, genome-wide patterns of shared genetic risk (Pouget et al., Hum Mol Genet, PMID: 31211845; Tylee et al., Am J Med Genet B Neuropsychiatr Genet 2018, PMID: 30325587). Some cases of psychosis involve autoantibodies against the NMDA receptor, AMPA receptor, or other synaptic proteins (reviewed in Dalmau et al, Lancet Neurol 2011, PMID: 21163445). The related autoimmune conditions lupus and Sjogren&#39;s Syndrome also involve the development of autoantibodies. The possibility that neuropsychiatric disorders can have molecular mechanisms in common with autoimmune disorders - for example, that psychosis involves an inflammatory or autoimmune component in some patients, or that immune molecules are re-used in the brain to underlie other important biological activities (Stevens et al., Cell 2007, PMID: 18083105) - could open novel therapeutic possibilities for neuropsychiatric disorders. At a genetic level, the strongest genetic associations of schizophrenia, lupus, and Sjogren&#39;s Syndrome to common genetic variation involve associations to genetic markers in the Major Histocompatibility Complex (MHC) locus. Bipolar disorder in some studies also associates with variation in or near the MHC locus, though less strongly than schizophrenia does. Intriguingly, the same specific SNPs appear to associate strongly with schizophrenia, lupus, and Sjogren&#39;s; these strongly associating SNPs span a genomic segment that includes the HLA class II genes (which have an important role in antibody production) and the complement component 4 (C4) genes. The specific genes and alleles responsible for these associations need to be completely defined, and the extent to which they represent shared or distinct genetic influences in neuropsychiatric and autoimmune illnesses needs to be clarified. The complement component 4 (C4A and C4B) genes are present in the MHC locus, between the class I and class II HLA genes. C4A and C4B commonly vary in genomic copy number and encode complement proteins with distinct affinities for molecular targets. The complex genetic variation at C4 - arising from many alleles with different numbers of C4A and C4B genes - has been challenging to analyze in large cohorts. We recently developed an approach to this problem based on imputation: people share long haplotypes with the same combinations of SNP and C4 alleles, such that C4A and C4B gene copy numbers can be imputed from SNP data (Sekar et al., Nature 2016, PMID: 26814963). In the current work, to analyze C4 in large cohorts, we developed a way to identify C4 alleles from whole-genome sequence (WGS) data, then analyzed WGS data from 1,234 individuals to create a large multi-ancestry panel of 2,530 reference haplotypes of MHC SNPs and C4 alleles that can then be imputed into still-larger cohorts for which SNP data are available. With this dbGaP submission, we make this reference panel available for other studies. Protocols and software for imputing C4 alleles into genome-wide SNP data, and for performing molecular analyses on the C4 genes (such as direct measurement of copy number from genomic DNA), can be found on the McCarroll Lab web site (http://mccarrolllab.org/resources). We are also working to create additional reference panels for imputation of C4 alleles that will be based on still-larger and more diverse population samples; links to these will also be available on the McCarroll Lab web site as we create and validate them.

  Study phs001992

• STAMPEED: Northern Finland Birth Cohort 1966 (NFBC1966)

  The Northern Finland Birth Cohorts program (NFBC) was initiated in the 1960s in the two northernmost provinces of Finland to study risk factors involved in pre-term birth and intrauterine growth retardation, and the consequences of these early adverse events on subsequent morbidity and mortality. The uniqueness of NBFCs is that the data of the cohorts were obtained from early fetal life (including maternal health during pregnancy) to adulthood. The NFBC1966 includes 12,058 live births to mothers in the two northern-most provinces of Finland. Two decades later, a second cohort of 9432 births was obtained (NFBC1986). In NFBC1966 pregnancies were followed prospectively from the first antenatal contact (10-16th week). After birth, the offspring were examined and then again underwent clinical evaluation at ages 1y, 7y, 14-16y and 31y. At each visit, a wide range of phenotypic, lifestyle and demographic data were gathered by questionnaires and clinical examinations. For the most part, NFBC1986 has undergone similar evaluations to NFBC1966. Linkage to national registries includes hospitalization, deaths, education, medication, pensions, and provides up-to-date demographic and clinical information for members of both cohorts. DNA samples were obtained from 5,923 subjects from NFBC1966 and 6688 subjects from NFBC1986. Data coverage, 96% of all births in 1966 and 99% in 1986, is highly representative for the whole population. The NFBC program comprises more than 20 different projects coordinated by the Center of Lifecourse Disease studies in Northern Finland (COLD) at Oulu University. The prospective data collected from the NFBCs form a unique resource, allowing the study of disease emergence, and of the importance of genetic, biological, social and behavioral risk factors. The genome-wide association (GWA) study sponsored through the STAMPEED program of NHLBI employed genomic DNA samples previously collected by the NFBC1966 study and stored in the DNA repository of the National Institute for Health and Welfare, Finland. This NHLBI sponsored RO1 project aimed to identify genetic variants contributing to metabolic and cardiovascular diseases (CVD). In addition to de-identified genome wide genotypic data, a selected list of phenotypic data related to CVD including weight, height, BMI, HDL, LDL, total cholesterol, triglyceride, glucose, insulin and fasting status, are also available in dbGaP. A summary of the GWAS for the NFBC1966 cardiovascular risk traits can be found in Sabatti et al., Nature Genetics 41: 35-46, 2009, PMID: 19060910. The version 2 release of this study contains sequence data from seventeen loci associated with levels of triglyceride, HDL-C, LDL-C, total cholesterol, fasting plasma glucose, and fasting plasma insulin (Kathiresan et al. 2008, Willer et al. 2008, Sabatti et al. 2009, Dupuis et al. 2010, Teslovich et al. 2010). At each locus, protein-coding regions and 5&#39; and 3&#39; untranslated regions of genes nearest to single nucleotide polymorphisms showing genome-wide significant association with metabolic syndrome-related traits, were sequenced. Targeted Illumina sequencing of 78 genes (~270kb) using 150bp probes was performed on 4943 subjects of the Northern Finland Birth Cohort 1966 (NFBC1966). Whole exome sequencing on the Illumina platform was carried out on 586 of those participants. The sequencing study is part of a larger project that is funded by the National Human Genome Research Institute&#39;s Allelic Spectrum in Common Disease Initiative, and comprises sequence data from more than 7000 individuals in two Finnish cohorts: NFBC1966 and the Finland-United States Investigation of NIDDM Genetics (FUSION) study.

  Study phs000276

• UCSF Sebaceous Carcinoma DAC for review of sequence data release from manuscript in Nature Communications, based in the UCSF Departments of Dermatology and Pathology

  Dac EGAC00001000850

• Early on-treatment changes in circulating tumor DNA fraction and response to enzalutamide or abiraterone in metastatic castration-resistant prostate cancer - Data Access Committee

  Dac EGAC00001003128