12405 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

in 17.22 milliseconds.

• Targeted_sequencing_of_genes_recurrently_mutated_in_AML___part2

  Genomic libraries will be generated from total genomic DNA derived from 4000 samples with Acute Myeloid Leukaemia. Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 64 Samples will be individually barcoded and subjected to up to one lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Study EGAS00001000570

• Analysis of Somatic Mutations in Pediatric AML FAB-M7 Subtype by Whole Transcriptome Sequencing

  High resolution analysis of DNA copy number abnormalities and loss-of-heterozygosity on acute myeloblastic leukemia samples utilizing SNP arrays has demonstrated that in contrast to pediatric ALL, de novo AML is characterized by a very low burden of genomic alterations (Radtke, et al., PNAS, 2009). Samples for this study represented a cross-section of the different subtypes of pediatric AML. The only AML subtype that was an outlier from the above observations was acute megakaryocytic leukemia (AML FAB-M7), with the majority of these cases being characterized by complex chromosomal rearrangements and a high number of copy number alterations. To more fully define the genomic landscape of this subtype, we performed transcriptome sequence analysis on 14 pediatric FAB-M7 cases and mutation recurrence screening in a panel of 62 adult and pediatric AML FAB-M7 samples using the Illumina platform. Our results identified chromosomal rearrangements resulting in the expression of novel fusion transcripts in 11/14 cases. Remarkably, in 7/14 cases we detected an inversion on chromosome 16 that results in the juxtaposition of the CBFA2T3 gene next to the GLIS2 gene resulting in a CBFA2T3-GLIS2 chimeric gene that encoded an in frame fusion protein. This fusion led to the acquisition or preservation of self-renewal in colony forming assays, providing functional evidence for a role in leukemogenesis. In addition to novel chimeric transcripts, we found mutations in genes previously identified to play a role in megakaryoblastic leukemia that carry a proliferative advantage to the cell, such as JAK2 and MPL. These data demonstrate that AML FAB-M7 is characterized by cooperating Class I and Class II mutations leading to leukemogenesis.

  Study phs000413

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

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. In this study, a novel SFT/HPC was characterized using whole genome sequencing.

  Dataset EGAD50000000038

• Sorted WGS for three samples

  This dataset contains Whole Genome Sequencing (WGS) data from two cell populations (myeloid and lymphoid) and the germline population sorted from a primary sample of the novel FOXF1/FENDRR ALL subtype. All the three samples are in bam file type.

  Dataset EGAD50000001792

• IBDCA_Edinburgh

  In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.

  Dataset EGAD00001001330

• Dataset for EGAS00001007937

  WGS, RNAseq, Methylation, variant calling analysis for a Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

  Dataset EGAD00001015412

• ExomeSeq Neoantigen Immunogenicity Landscapes

  Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies. Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood. To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted. We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit. We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment. These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders. Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score. Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment. Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.

  Study EGAS00001007508

• RNASeq Neoantigen Immunogenicity Landscape

  Immune checkpoint blockade (ICB) therapy is a cornerstone of oncologic treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and other malignancies. Neoantigen immunoediting drives ICB efficacy, yet the fundamental physiochemical characteristics of neoantigens and how neoantigen immunogenicity shapes treatment response remains poorly understood. To help address these questions, a prospective clinical trial of NSCLC patients treated with nivolumab was conducted. We assessed genomic alterations in tumors from 58 patients and performed large-scale neoepitope immunogenicity analyses, before and during treatment (CheckMate153, CA209-153). Tumors were analyzed by whole-exome and transcriptome sequencing. In responding patients, loss of mutation and neoantigen burden early during therapy associated with clinical benefit. We evaluated the immunogenicity of 1,453 candidate neoantigens and identified 502 neopeptides that bound to MHC I and 196 neopeptides that were immunogenically recognized by T cells in the setting of nivolumab treatment. These T cell reactive neoantigens were differentially present in clonal populations that underwent distinctive evolutionary trajectories across responders and nonresponders. Mapping these neoantigens to tumor clonal dynamics and clinical response revealed strong selection against immunogenic neoantigen harboring clones compared to non-immunogenic clones. Using this large collection of neoantigens, we identified position specific amino acid features related to immunogenicity, which we used to develop and validate an immunogenicity score. Changes in the genomic and neoantigen immunogenicity landscapes were accompanied by temporal changes in the tumor microenvironment. Nivolumab-induced microenvironmental evolution in NSCLC shared some similarities with that in melanoma, yet critical differences in immunologic programs were apparent from comparative network analysis between tumor types. This study provides unprecedented molecular portraits of the neoantigen landscapes underlying nivolumab’s mechanism of action.

  Study EGAS00001007509

• Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome

  Gray Platelet Syndrome (GPS) is a rare recessive bleeding disorder resulting from biallelic variants in NBEAL2. As part of a comprehensive evaluation of the phenotype and genotype in 47 patients with GPS, four different blood cell-types (platelets, neutrophils, monocytes, and CD4-lymphocytes) were evaluated using bulk RNA-seq in five patients and five controls. These data are deposited in this archive in FASTQ format.

  Dataset EGAD00001005950

• Whole_Exome_Sequencing_for_Characterization_of_Disease_Causing_Mutations_in_two_Pakistani_Families_Suffering_from_Autosomal_Recessive_Ocular_Disorders_

  We propose to use whole exome Agilent solutionprobes and paired end Illumina sequencing to sequence 4 individualsfrom two families suffering from novel autosomal recessive disease[microphthalmia, MOP (OMIM %251600) and non-syndromic persistenthyperplastic primary vitreous, PHPV (OMIM %611311)]. Selectedcandidate variants will subsequently be genotyped in the remainingfamily members in Pakistan with the aim of identifying the rarehomozygous recessive mutations responsible for the disease phenotype. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001000026