3930 results for "RNA AND sequencing OR transcriptome"

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• Profiling Genome-Wide Circulating ncRNAs for the Early Detection of Lung Cancer

  Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Although imaging techniques such as low-dose computed tomography (LDCT), combined with tissue biopsies, have improved early detection rates, current diagnostic approaches are often limited by high false-positive rates, invasiveness, and radiation exposure, which lead to misdiagnosis and increased patient burden. Therefore, there is an urgent need for minimally invasive, accurate, and safe diagnostic biomarkers, particularly those derived from liquid biopsies such as blood-based exosomal RNA.This dataset specifically focuses on plasma-derived exosomal small non-coding RNAs (sncRNAs).A total of 233 de-identified plasma samples were obtained from Rush University Medical Center, including 116 NSCLC patients and 117 non-cancer controls. Exosomes were isolated from plasma, RNA was extracted, and small RNA sequencing was performed using the Illumina NextSeq 500 platform. Data available through dbGaP include individual-level raw sequencing files (FASTQ) and basic phenotype annotations of the plasma cohort.A diagnostic model was initially developed using small RNA-seq data from 1,446 tissue samples obtained from TCGA and GEO, identifying a robust sncRNA signature that distinguished NSCLC from non-cancer samples with an AUC of 0.90 in hold-out tissue validation. This signature was subsequently validated in the plasma exosome cohort, achieving an AUC of 0.84 in independent validation. The model demonstrated consistent diagnostic performance across subgroups stratified by age, sex, smoking history, cancer stage, and NSCLC subtype. Survival and functional analyses further supported the clinical and biological relevance of the identified sncRNAs. It is hoped that this resource will contribute to a better understanding of the sncRNA expression landscape in NSCLC and promote the development of non-invasive biomarkers for early cancer detection. These data may be applied to the investigation of transcriptomic and other risk factors, provide insight into cancer screening, tumor progression mechanisms, and prognosis prediction, and ultimately support precision medicine for NSCLC.

  Study phs004166

• Immunogenomics of Malignant Brain Tumors

  We performed systematic and comprehensive multi-sector immunogenomic analyses on 93 samples from a cohort of 30 patients with primary or recurrent gliomas or metastatic brain tumors, representing the largest cohort of these brain cancers studied spatially to date. For each patient, we characterized multiple spatially distinct regions using whole-exome (WES), custom capture validation, RNA, and TCR-sequencing. Our findings underscore the significant differences in clonal architecture between gliomas and metastatic brain tumors which translates into distinct neoantigen landscapes and, in turn, tumor infiltrating T cell clonotypic diversity. These data therefore provide high resolution insights into the immunogenomic landscapes within malignant brain tumors which may inform tumor-specific therapeutic approaches.

  Study phs002612

• RNAseq RPKM

  RNA-seq data from ILC samples. This dataset includes counts normalized for sequencing depth and gene length.

  Dataset EGAD50000000828

• Paired healthy & tumor organoid Biobank _B16PON

  Organoid cultures derived from colorectal adenomas. RNA and DNA was isolated from these cultures for genome wide profiling.

  Dataset EGAD00001008949

• Medulloblastoma exome sequence analysis

  Medulloblastomas are the most common malignant brain tumors in children. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles. Here, we utilized whole exome hybrid capture and Illumina sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, to our knowledge novel findings in medulloblastoma and all cancer. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma. "Reprinted from 'MEDULLOBLASTOMA EXOME SEQUENCING UNCOVERS SUBTYPE-SPECIFIC SOMATIC MUTATION', with permission from Nature"

  Study phs000504

• Trisomy 21 Dosage Compensation Map (T21DoCoMap)

  Excess gene dosage from human chromosome 21 (HSA21), due to trisomy or translocation of HSA21 material, causes Down syndrome (DS). We derived trisomy 21 (T21) induced pluripotent stem cells (iPSCs) alongside otherwise isogenic euploid controls from mosaic DS fibroblasts (GM00260, first described in Lubiniecki et al., PMID: 225951) of the NIGMS genetic cell repository, to enable analysis of whole-chromosomal and individual gene dosage imbalance in the context of in vitro models of DS development. Virtual karyotyping (by Infinium CytoSNP-850k), and phased genotyping (by linked-read whole-genome sequencing) of the resulting iPSC lines provide a deeply-characterized genomic platform for dissection of HSA21 gene dosage. We apply this highly unique resource to allelic analysis of mRNA sequencing of iPSCs and differentiated neural lineages, and demonstrate its utility in the context of inducible HSA21 dosage compensation. To this end, we equipped one distinct HSA21 copy with a doxycycline-inducible XIST transgene, which endogenously silences one X in 46,XX females. Standard and allele-specific RNA-seq analysis confirms mono-allelic T21 silencing to be virtually complete and irreversible, further supported by DNA methylation data (Infinium methylEPIC). This full-length HSA21 map of phased single-nucleotide and insertion/deletion variants enables allele-specific applications for gene-level dissection T21 dosage effects. Because our XIST remains inducible in post-mitotic T21 neurons and astrocytes, we perform single-nuclei RNA-seq to demonstrate XIST efficiently represses genes even after terminal differentiation.

  Study phs002397

• A novel orthotopic patient-derived xenograft model of radiation-induced glioma following medulloblastoma

  Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phospho-S6, -4EBP1 and -ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.

  Study EGAS00001004709

• Next Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

  Putative oncogenic pathways in squamous cell lung cancer have been recently characterized, although their biologic repercussions in patients is largely unknown. This study sought to discover potential clinical manifestations of major pathways in squamous cell lung cancer, particularly the PI3K pathway. Two key findings emerged: patients with stage IV squamous cell lung cancer whose tumors harbored upstream PI3K aberrations had significantly worse survival and a higher burden of metastatic disease. In addition, brain metastases were significantly more common in these patients than in others. Paired lung primary/brain metastasis genotyping, including RNA sequencing and whole exome sequencing, uncovered a high degree of genetic heterogeneity between lung/brain pairs, and identified potential regulators of the metastatic process to brain.

  Study phs000907

• High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. These tumors were profiled using whole-genome sequencing (WGS) or whole-exome sequencing (WES) to identify somatic mutations, WGS or low-pass WGS to detect copy number alterations, targeted capture sequencing to assess MYC and BCL2 structural variants, and RNA sequencing. The genetic features of HGBCL-NOS were compared to those of diffuse large B-cell lymphoma (DLBCL-NOS) and EBV-negative adult Burkitt lymphoma (BL). DLBCL-NOS tumors underwent targeted capture sequencing using a panel of 125 genes recurrently mutated in aggressive B-cell lymphomas. BL biopsies were drawn from the Burkitt Lymphoma Genome Sequencing Project and had available WGS (dbGaP Study Accession: phs000527.v18.p6).

  Study EGAS50000000932

• CD4+ cell transcriptional profiling by RNA sequencing

  We use next generation sequencing to investigate the different transcriptomes of closely related CD4+ T-cells from healthy human donors to elucidate the genetic programs that underlie their specialized immune functions. Six cell types were included: Regulatory T-cells (CD25hiCD127low/neg with >95% FOXP3+ purity), regulatory T-cells activated using PMA/ionomycin, CD25-CD45RA+ ('naive' helper T-cells), CD25-CD45RO+ ('memory' helper T-cells), activated Th17 cells (>98% IL17A+ purity) and activated IL17-CD4+ T-cells (called 'ThPI'). Poly-T capture beads were used to isolate mRNA from total RNA, and fragment sizes of ~200 were sequenced from both ends on Illumina's genome analyzer. We confirm many of the canonical signature genes of T-cell populations, but also discover new genes whose expression is limited to specific CD4 T-cell lineages, including long non-coding RNAs. Additionally, we find that genes encoded at loci linked to multiple human autoimmune diseases are enriched for preferential expression upon T-cell activation, suggesting that an aberrant response to T-cell activation is fundamental to pathogenesis.

  Study phs000626