14977 results for "cancer studies using rna-seq"

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• Targeted de novo phasing and long-range assembly by template mutagenesis

  Long-range sequencing with low error rate has been challenging. Sequence assembly and phasing usually require a high-quality reference genome for mapping, so working on highly-variable genomic regions or regions with no reference genome information would be difficult. In this study, we describe novel bench protocols and algorithms to obtain ultra-low-error-rate haplotype-phased sequence assemblies of regions 10 KB in length using a short-read sequencing platform that simultaneously solves the above two problems. We accomplish this by imprinting each template strand from a target region with a dense and unique mutation pattern. The mutation process randomly and independently converts ~50% of cytosines to uracils. Short-read sequencing libraries are made from both mutated and unmutated templates. A conservative de Bruijn graph approach seeds an assembly of the mutated templates, which we then extend by mapping paired-end reads. We next partition the template assemblies into two or more haplotypes after using the unmutated sequence library to recover almost all of the mutated bases. The final haplotype is assembled and corrected for residual template mutations and PCR errors. We obtain per-base-error rates below 10 9. We apply this method to a human family, correctly assembling and phasing three genomic intervals, including the highly polymorphic HLA-B gene.

  Dataset EGAD00001008444

• TB-DAR Whole Genome Sequencing Study

  116 Whole Genome Sequencing (WGS) samples from the TB-DAR study, based on a cohort of adult pulmonary tuberculosis patients recruited in Dar es Salaam, Tanzania. WGS was performed at the Health2030 Genome Center in Geneva on the Illumina NovaSeq 6000 instrument (Illumina Inc, San Diego CA, USA), starting from1μg of whole blood genomic DNA and using Illumina TruSeq DNA PCR-Free reagents for library preparation and the 150nt paired-end sequencing configuration. Average coverage was above 30X for 75 samples, between 10X and 30Xfor 40 samples, and approximately 8X for a single sample. Sequencing reads were aligned to the GRCh38 (GCA_000001405.15) reference genome using bwa (Version 0.7.17).

  Dataset EGAD00001008400

• Institut Curie Neuroblastoma Whole Genome Sequencing Diagnosis Relapse

  Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table 1). Following alignment with BWA (Li et al., Oxford J, 2009 Jul) allowing up to 4% of mismatches, bam files were cleaned up according to the Genome Analysis Toolkit (GATK) recommendations (Van der Auwera et al., Current Protocols in Bioinformatics, 2013, picard-1.45, GenomeAnalysisTK-2.2-16). Variant calling was performed in parallel using 3 variant callers: GenomeAnalysisTK-2.2-16, Samtools-0.1.18 and MuTect-1.1.4 (McKenna et al., Genome Res, 2010; Li et al., Oxford J, 2009 Aug; Cibulskis et al., Nature, 2013). Annovar-v2012-10-23 with cosmic-v64 and dbsnp-v137 were used for the annotation and RefSeq for the structural annotation. For GATK and Samtools, single nucleotide variants (SNVs) with a quality under 30, a depth of coverage under 6 or with less than 2 reads supporting the variant were filter out. MuTect with parameters following GATK and Samtools thresholds have been used to filter our irrelevant variants. .SNVs within and around exons of coding genes overlapping splice sites.. Then,variants reported in more than 1% of the population in the 1000 genomes (1000gAprl_2012) or Exome Sequencing Project (ESP6500) have been discarded in order to filter polymorphisms. Finally, synonymous variants were filtered out. MuTect focuses on somatic by filtering with constitutional sample. Mpileup comparison between constitutional and somatic DNAs allowed us to focus also on tumor specific SNVs with GATK and Samtools. Finally, every SNV called by our pipeline and also supported in any constitutional samples were filtered our in order to prevent putative constitutional DNA coverage deficiency. Then we analyzed CNVs (copy number variants) with HMMcopy-v0.1.1 (Gavin et al., Genome Res, 2012) and control-FREEC-v6.7 (Boeva et al., Bioinformatics 2011) with a respective window of 2000bp and 1000 bp, and auto-correction of normal contamination of tumor samples for Control-FREEC. Finally we explored Structural variants (SVs) including deletions, inversions, tandem duplications and translocations using DELLY-v0.5.5 with standard parameters (Rausch et al., Oxford J, 2012). In tumors, at least 10 supporting reads were required to make a call and 5 supporting reads for the sample NB0175 with a coverage of only 40X (see table 2). To predict SVs in constitutional samples for subsequent somatic filtering, only 2 supporting reads were required in order not to miss one. To identify somatic events, all the SVs in each normal sample were first flanked by 500 bp in both directions and any SVs called in a tumor sample which was in the combined flanked regions of respective normal sample was removed (see graph 1). Deletions with more than 5 genes impacted or larger than 1Mb and inversions or tandem duplications covering more than 4 genes, were removed. We focused on exonic and splicing events for deletions, inversions, and tandem duplications. For translocation, we keep all SVs that occurred in intronic, exonic, 5'UTR, upstream or splicing regions. Bioinformatics detection of variations with Deep sequencing approach Once PE reads merged and adaptors trimmed by SeqPrep with default parameters, merged reads were aligned via the BWA (Li H. and Durbin R. 2009 PMID 19451168) allowing up to 1 differences in the 22-base-long seeds and reporting only unique alignments. Only reads having a mapping quality 20 or more have been further analysed. Variant calling software was not used, since we aimed to predict variations at low frequencies, observed in less than 1% of reads. Such variants require a custom approach. Using DepthOfCoverage functions of the Genome Analysis Toolkit (GATK) v2.13.2 (McKenna A, et al., 2010 Genome Research PMID: 20644199), we focused on high quality coverage of bases A, C, G and T at the targeted variant position. Depth of coverage of each base following a mapping quality higher than 20 and a base quality higher than 10 have been taken into account in order to focus only on high quality data. Aiming to determine the background level of variability at the studied regions, 10 control samples were included in the analysis. The same approach and filtering criteria have been applied as introduced above over the entire amplicons. In order to highlight variants, for each sample the frequencies of each bases at each amplicon position were then compared to those observed in the set of controls. Statistical analyses were performed with the R statistical software (http://www.R-project.org). Fisher’s exact two-sided tests with a Bonferroni correction were performed to compare percentages of bases between the data sets, i.e. for a given base between a case and the controls. Finally, significant variations were filtered-in once (i) a significant increase in the percentage of avariant base and (ii) a significant decrease in the percentage of it's reference base following our p.values criteria was observed (p.val < 0.05).

  Study EGAS00001001184

• CDK4/6 inhibition in advanced chordoma: final results of the NCT PMO-1601

  Background. Chordoma is a rare bone tumor with no approved systemic therapy. Inactivation of the tumor suppressor p16 (encoded by CDKN2A) leads to aberrant cyclin D-CDK4/6-RB pathway activity, which can be inhibited by palbociclib in chordoma cell lines. Patients and Methods. We conducted a phase II single-arm, open-labeled trial on palbociclib in adult patients with advanced chordomas with p16 loss (by immunohistochemistry) or CDKN2A loss (by genomic analysis) and CDK4/6 and RB1 presence (by immunohistochemistry or RNA-Sequencing). Patients received 125mg palbociclib once daily for 21 days in a 28-day cycle. The study used a Simon optimal 2-stage design. The primary endpoint was disease control rate after six cycles. Response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival, overall survival, and biomarker analysis. The study was considered positive if 25% of patients reached the primary endpoint. Results. Between December 2017 and April 2023, 28 patients (median age 60 years, range 31-84) were enrolled. After a median follow-up of 28 months, the disease control rate was 39%, with 11 out of 28 patients achieving stable disease. No objective responses were observed. The median progression-free survival was 5.6 months, and the median overall survival was 24.6 months. Treatment was well tolerated without new safety signals. CDKN2A deletions were the most common genomic alterations underlying p16 loss and were accompanied by MTAP co-deletion. There was no correlation between responder phenotypes by immunohistochemistry and outcome. RNA-based analysis showed heterogeneous pathways deregulation at study entry suggesting underlying primary resistance mechanisms Conclusion. This trial met its primary endpoint with a 39% disease control rate, though antitumor activity was modest. Molecularly tailored combination therapies should be considered to improve efficacy. (ClinicalTrials.gov number, NCT03110744).

  Study EGAS00001007985

• Molecular characterization of Barrett’s esophagus at single cell resolution

  Backgrounds & Aims: Patient with Barrett’s esophagus (BE) have an increased risk to develop esophageal adenocarcinoma and are under periodical endoscopic surveillance for malignant transformation. Pathologists distinguish between different BE stages to identify high-risk patients, but this process remains difficult as stage-specific markers are still missing. We established BE organoid cultures, applied single cell sequencing approaches to identify differences in gene expression and genomic alterations, and validated candidate genes for their predictive value on histological sections. Methods: We collected 43 epithelial biopsies from 21 patients, established organoids for the clonal expansion of matching healthy and diseased tissue from two patients to identify genomic alterations by whole genome sequencing (WGS). We performed single cell DNA-sequencing (scDNAseq) to analyse DNA alterations within biopsies from 8 patients and single cell RNA-sequencing (scRNAseq) to identify gene expression differences between BE stages from 19 patients. Candidate marker genes were then validated by RNA in situ hybridization experiments on histological resection specimen. Results: Most BE biopsies were chromosomal stable (CS) and their single base substitution (SBS) signatures were indistinguishable from the healthy control tissues. Dysplastic BE cells contained areas of chromosomal instabilities (CIN), which differed by the presence of the SBS17 signatures from biopsy-matching CS cells or patient-matching healthy control cells. Such CIN areas affected efficient clustering of the scRNAseq data. We identified two sets of marker genes (SLC5A5, PSCA, LIPF and ANPEP, CEACAM6, REG4), which distinguish columnar BE epithelium from non-dysplastic/dysplastic stages. CLDN2 allowed the distinction between dysplastic and more advanced stages as its expression level increased and spread in dysplastic BE glands. Conclusions: Molecular characterization of BE samples identified a correlation between the presence of CIN and COSMIC signature 17, and we report seven marker genes that help in distinguishing different BE stages.

  Study EGAS00001005221

• Single-cell profiling of neoantigen-specific T cells in lung cancers treated with neoadjuvant PD-1 blockade

  This dataset includes 406 samples from non small cell lung cancer patients treated with neoadjuvant anti-PD-1. The Single Cell 5’ V(D)J and 5’ DGE kits (10X Genomics) were used to capture immune repertoire information and gene expression from the same cell in an emulsion-based protocol at the single cell level. Libraries were generated and sequenced on an Illumina NovaSeq instrument using 2x150bp paired end sequencing.

  Dataset EGAD00001007728

• EGAD00010000266

  Metabric breast cancer samples (Genotype raw data)

  Dataset EGAD00010000266

• ICGC Prostate Cancer Whole Genome Sequencing

  A small subsample of EGAD00001000689. Please do not use.

  Dataset EGAD00001000263

• Whole exome sequencing of bulk primary tumor (and one lymph node metastasis) and matched blood of six non-metastatic breast cancer patients

  Dataset EGAD00001002746

• methylation_ec

  Raw methylation data from cervical samples in individuals with endometrial cancer.

  Dataset EGAD00010002084

• methylation_oc

  Raw methylation data from cervical samples in individuals with ovarian cancer.

  Dataset EGAD00010002086

• VCF dataset of Colorectal Cancer Synthetic genomes

  This dataset contains genomic variants data from VCF files of four patients synthetically generated in the EOSC4Cancer project

  Dataset EGAD50000000314

• germline pathogenic variants found in African patients of prostate cancer

  70 new blood samples added in this project

  Study EGAS50000001132

• The_mutational_landscape_of_recurrent_Glioblastome_multiforme

  Targeted gene screen of approx 120 patients with primary GBM and recurrent samples.

  Study EGAS00001001764

• OT2_Illumina_WXS_MET

  Whole-exome sequencing on Illumina HiSeq2000/2500 of colorectal cancer metastasis sample (OT2_cohort)

  Dataset EGAD00001003379

• Illumina_WXS_T

  Whole-exome sequencing on Illumina HiSeq2000/2500 of colorectal cancer primary tumor sample

  Dataset EGAD00001002099

• OT2_Illumina_WGS_T

  Whole-genome sequencing on Illumina HiSeq2000/2500 of colorectal cancer primary tumor sample (OT2_cohort)

  Dataset EGAD00001003375

• Wilms_Tumour_organoid_sequencing_WGS

  This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids

  Study EGAS00001002692

• Placental_genomics

  The aim of this study is to define the mutational landscape of placentas.

  Study EGAS00001003297

• Genetic Susceptibility and Biomarkers of Platinum-Related Toxicities

  The Platinum Study is an R01-funded, multicenter study of testicular cancer survivors that characterizes both long-term cisplatin-induced peripheral neuropathy (CisIPN) and cisplatin-associated ototoxicity, i.e., permanent, bilateral hearing loss. We collected data abstracted from medical records (e.g., cumulative cisplatin dose), conducted audiometric examinations, and administered self-report questionnaires, which included CisIPN symptoms.

  Study phs001621

• Exome Sequencing of Pleuropulmonary Blastoma

  Pleuropulmonary blastoma (PPB) is a rare, aggressive pediatric cancer arising from the lung or pleural cavity. In this study, we sequenced and analyzed the exomes of 15 PPB matched tumor and normal pairs. This study is part of a larger effort to characterize pediatric cancers as part of the Slim Initiative for Genomic Medicine (SIGMA) project.

  Study phs000543

• Single cell transcriptomic profiles of advanced melanoma patients treated with checkpoint inhibitor immunotherapy

  Little is known about the resistant clones within the tumour ecosystem treated with immunotherapy. This work provides a comprehensive and integrative analysis of each individual non-responding melanoma patients, including clinical features integrated with single cell analysis, which is critical to understand features of resistance in order to improve cancer patients’ outcomes.

  Study EGAS50000000339

• PDX gene expression

  Investigation of the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1amp high-grade serous ovarian cancer (HGSOC) models. We analyzed gene expression in five patient derived xenografts (PDX) that responded to CHK1i and three PDX that had a poor response to CHK1i.

  Study EGAS50000000084

• Dataset of 2485 CD8 T cells from non-muscle-invasive bladder cancer patients in context of BCG treatment

  FASTQ files from scRNAseq (smartseq2 protocol) from 2485 CD8 T cells from 4 non-muscle-invasive bladder cancer patients who received BCG treatment (induction treatment of 6 weekly instillations). Concerning the 'phenotype' column in metadata : pre-treatment samples include tumor samples ('Tumor') and normal adjacent bladder tissue ('Extratumor'). For post-treatment samples : no residual tumor was found in the bladder of the 4 patients after the BCG treatment . The post-treatment samples with 'Tumor' as phenotype denote samples from macroscopically suspect zones, but with microscopically no tumor detected.

  Dataset EGAD50000002007

• Genomic Data from Patients with Advanced Rare Cancers Treated with Pembrolizumab

  Rare cancers lack effective evidence-based treatments despite contributing substantially to cancer-related mortality. The goal of this study is to identify molecular biomarkers associated with response to pembrolizumab in patients with advanced rare cancers.This dataset includes genomic profiling generated from patients enrolled in an investigator-initiated phase II basket trial of pembrolizumab.

  Study EGAS50000001508

• Transcriptomic Data from Patients with Advanced Rare Cancers Treated with Pembrolizumab

  Rare cancers lack effective evidence-based treatments despite contributing substantially to cancer-related mortality. The goal of this study is to identify molecular biomarkers associated with response to pembrolizumab in patients with advanced rare cancers.This dataset includes transcriptomic profiling generated from patients enrolled in an investigator-initiated phase II basket trial of pembrolizumab.

  Study EGAS50000001509

• 2014 chunnam AML analysis

  2014 AML analysis is conducted with samples collected from Chunnam universty. 67 paired samples are belong to this project. The study was designed to examine the molecular abnormalities from leukemic patients at initial diagnosis in comparison with corresponding germ line control (saliva samples). The results of WXS were analyzed by Mutect for ranking cancer variants and creating mutational matrix.

  Study EGAS00001001082

• MutWP5: CRUK Mutographs of Cancer: Breast: BRCA Carriers (Exome) (2020-01-29)

  Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastectomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with cancer. . This dataset contains all the data available for this study on 2020-01-29.

  Dataset EGAD00001005921

• MutWP5: CRUK Mutographs of Cancer: Breast: BRCA Carriers (Targeted) (2020-01-29)

  Sequencing of LCM-derived microbiopsies from 20 women who underwent risk-reducing reduction mastectomies due to germline BRCA1/2. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Targeted data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who had cosmetic breast reduction surgeries and those with cancer. . This dataset contains all the data available for this study on 2020-01-29.

  Dataset EGAD00001005920

• Three large nuclear families in which a single child per family was diagnosed with cancer

  We collected saliva samples from three nuclear families having 4, 5, and 7 children, respectively. One child in each nfamily had been diagnosed with a pediatric tumor, and neither parent had been diagnosed with cancer. Diagnoses included Wilms tumor, low-grade astrocytoma, and Burkitt’s lymphoma, respectively. We used whole-genome sequencing to profile normal cells from each family member and a linked-read technology.

  Dataset EGAD00001007709