15020 results for "cancer studies using rna-seq"

in 19.16 milliseconds.

• Preeclampsia InterPregGen Consortium: Whole Genome Sequencing of 100 unrelated Kazakhs (DNA samples from the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan; Gulnara Svyatova, Principal Investigator

  Whole genome sequencing of 100 unrelated Kazakhs in order to impute genotypes into PE cases and controls from Kazakhstan and to provide genetic data and infrastructure for future genetic studies in Kazakhstan and Central Asia more generally and to fill a gap in worldwide information as Central Asia is not adequately represented in available genomic data. This dataset is one component of the InterPregGen FP7 project. DNA samples for this component were collected by InterPregGen Consortium collaborators at the Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan (Gulnara Svyatova, Principal Investigator)

  Dataset EGAD00001005467

• PAK4 inhibition improves PD-1 blockade immunotherapy

  Introduction with rationale and aims for study Immune checkpoint blockade therapies have significantly altered the current landscape of cancer treatment. However, this immunotherapy still fails more often than it succeeds. There are now evidences that the lack of tumour infiltration by immune cells is the main mechanism of primary resistance to PD‐1 blockade therapies for cancer. It has been postulated that cancer cell‐intrinsic mechanisms may actively exclude T cells from tumours, suggesting that the finding of actionable molecules that could be inhibited to increase T cell infiltration may synergize with checkpoint inhibitor immunotherapy. With the idea of finding potential drivers of immune exclusion, we performed RNA sequencing analysis of biopsies from melanoma patients and compared the transcriptomic differences of samples that where infiltrated with those that did not have immune infiltration. Methods RNAseq analysis of gene expressions on biopsies from melanoma patients treated with checkpoint blockade were analysed. We focused on the variable of "infiltration: yes or no,", e.g. tumors that were well infiltrated by immune cells with those that kept immune cells out. Sequencing revealed a list of genes whose expression differed between the infiltrated and noninfiltrated tumors. The kinase PAK4 stood out as a good candidate for inhibition treatment in the future as it was consistently enriched in the samples without immune infiltration. To test whether immunotherapy would work better if we deleted PAK4, we first knocked out PAK4, using CRISPR‐Cas9, in the ‐resistant melanoma cell line, B16. Then they injected the melanoma cells into mice and observed that PAK4 KO tumours now responded to PD‐1 blockade. In order to elucidate whether pharmacological inhibition of PAK4 could recapitulate the results observed in the B16 PAK4 KO tumours, we obtained the PAK4 inhibitor, KPT-9274, from Karyopharm Therapeutics. Indeed, inhibiting PAK4 in combination with anti‐PD‐1 immunotherapy significantly slowed the growth of the B16 melanomas more than either drug alone. Results and Conclusions Transcriptomic analysis of melanoma tumors that were well infiltrated by immune cells with those that kept immune cells out revealed a list of genes whose expression differed between the infiltrated and non-infiltrated tumours. The result suggests that p21 activated kinase 4 (PAK4) is enriched in non-responding tumour biopsies with low T cell and dendritic cell infiltration. In addition, PAK4 decreased WNT activity, a signalling pathway that has previously been involved in immune exclusion. In mouse models, genetic deletion of PAK4 increased T cell infiltration and reversed resistance to PD‐1 blockade in a CD8 T cell-dependent manner. Furthermore, combination of with the PAK4 inhibitor, KPT-9274, improved anti‐tumour responses compared to anti‐PD‐1 alone. Therefore, high PAK4 expression is correlated with low T cell and dendritic cell infiltration and lack of response to PD‐1 blockade, which could be reversed with PAK4 inhibition. The data establish a rationale for targeting this kinase with inhibitors in combination with immune checkpoint inhibitors for patients. Future work and data that we can anticipate for this study Oncogenic signalling pathways and specially the WNT signalling pathway, have been associated with lack of immune infiltration and resistance to PD‐1 blockade therapies. Here, we show that PAK4 overcome resistance to PD‐1 blockade while significantly decreases WNT signalling activity. Therefore, it constitutes the first potential druggable target that is able to reverse oncogenic driven immune cell exclusion. However, the fully mechanism whereby PAK4 sensitizes tumours to immunotherapy remains to be fully elucidated. It is necessary to address whether PAK4 inhibition overcomes resistance through WNT signalling inhibition or if other signalling pathways are involved in the observed phenotype.

  Study phs001919

• Targeted sequencing

  Paired-end BAM files with associated index files of 15 AML samples were generated using Agilent SureSelect XT library capture system using a custom panel as described before Takahashi et al Blood 2018. Libraries were sequenced using Illumina HiSeq 2500.

  Dataset EGAD00001007671

• GenomeDenmark Phase 2 - variants called on chrY for 62 males.

  Variants on the Y chromosome for 62 danish males in VCF format from the GenomeDenmark Phase 2 cohort. Variants were called using reference based approaches such as the haplotype-caller module from GATK and using alignment of denovo assemblies to the reference using ASMvar.

  Dataset EGAD00001003186

• Whole genome sequencing of breast cancer and related clones

  Paired WGA (whole-genome amplificated) samples from 65 single cell-derived organoids and six fresh single cell-derived organoid samples both of which were established from normal mammary epithelial cells, 84 FFPE LCM (laser-capture microdissection) samples of breast cancer and related clones, 79 fresh-frozen LCM samples of non-cancer lobules of breast cancer patients, and 36 matched germline controls were subjected to whole genome sequencing using NovaSeq 6000 system (Illumina) or DNBSEQ-G400RS (MGI Tech).

  Dataset EGAD00001010833

• Asian Indian Diabetic Heart Study (AIDHS) /Sikh Diabetes Study (SDS)

  The Punjabi Sikh population is a well-defined, carefully collected homogeneous sample from northern India and the US. It has unique characteristics, which are ideal for genetic studies. Sikhs are strictly a non-smoking population and about 50% of participants are life-long vegetarians. All subjects included in the genome-wide association studies (GWAS) were recruited from one geographical location. Our population demonstrates a strong familial clustering of type 2 diabetes and related cardio-metabolic disorders that may be genetic and we believe that the contribution of alleles at specific loci are likely to be unique to Punjabi Asians compared to Europeans. Our group first showed that the association of a common variant at rs9939609 in the FTO (fat mass and obesity) gene in South Asians was independent of BMI (PMID:18598350) in contrast to Europeans where the association of same variant with T2D is mediated through obesity (PMID:17434869). These findings were later confirmed in an independent sample of South Indians (PMID:19005641), Pakistanis (PMID:21294771), and even East and South Asians in a large meta-analyses study comprising 96,551 individuals (PMID: 22109280). Earlier reported association of MTNR1B with fasting glucose concentrations and type 2 diabetes in European GWAS could not be confirmed in our Sikh cohort. On the other hand, our study revealed, for the first time, a significant protective association of another less common variant in MTNR1B with fasting glucose levels that was modulated by obesity. Ours was the first report that suggested that the low CETP activity was associated with higher CAD risk (PMID:22143414) in South Asians and that the genetic effects are significantly modulated by environmental factors (alcohol consumption). Our recent GWAS on type 2 diabetes has identified a novel locus at chromosome 13q12 in the SGCG gene (p=1.82x10-8) associated with type 2 diabetes (PMID:23300278) in Punjabi Sikhs. From these findings, we are optimistic that our resource will provide new insights to gene functions in the diabetic pathway and better help researchers to understand and translate these insights to novel therapeutic treatment and early prevention to T2D that may be important beyond Indians.

  Study phs000583

• Ulcerative Colitis Human Microbiome Project (UCHMP)

  The aims of the multi-center Ulcerative Colitis Human Microbiome Project (UCHMP) are to examine the role of the enteric microbiome in causing human ulcerative colitis, specifically the development of pouchitis. Pouchitis is an inflammatory condition of the surgically-created ileoanal pouch that serves as a pseudo-rectum in patients with ulcerative colitis who have undergone a total colectomy. It is a condition unique to ulcerative colitis (UC), as it rarely occurs in non-UC patients who have the same procedure. Within one year, about 50% of patients will develop pouchitis. The condition is almost certainly due to aspects of the pouch microbiota on a background of genetic susceptibility, as most patients respond to treatment with antibiotics. While there have been reports on the microbiota in pouchitis patients, all have been performed after the inflammatory process is initiated, rendering interpretation of the results difficult, as the inflammatory process itself will change the microbiota. Our project is therefore unique and possibly the only opportunity in the role of the enteric microbiome in IBD in a prospective manner, thereby establishing potentially important causal relationships between microbiota structure or function and development of UC.The studies also offer two additional advantages. First, the development of the pouch microbiota can be observed prospectively. Second, the cause of antibiotic treatment failure in some patients with pouchitis may be revealed. The two aims are (1) to identify causal factors in the structure and/or function of the enteric microbiota in the development of pouchitis, and (2) to determine the basis of treatment failure in UC pouchitis patients. Our analyses will include serial measurements of enteric microbial structure (16S rRNA gene-based), function (metagenomics and functional candidate genes), and cultivation, the latter to enhance interpretation of gene sequences derived from metagenomes and targeted gene surveys (either functional or 16S genes). The insights gained from these studies will help us understand the fundamental and causative roles of the enteric microbiome in human inflammatory bowel diseases (IBD). This information will be the basis for developing strategies to restore host-microbial relationships to prevent and treat IBD.

  Study phs000262

• Dataset for WGS and RNA melanoma samples

  This dataset contains WGS and RNA sequencing data for 4 melanoma samples. Sequencing was performed on Illumina Novaseq 6000 and Illumina HiSeq X. The sequencing was always paired.

  Dataset EGAD50000000093

• B cell single cell sequencing (RNA + VDJ) - Autoproliferation

  10X 3' (RNA) and 10X 5' (VDJ) samples of B cells (non-proliferating/hi and autoproliferating/Dim) for healthy donor and Multiple sclerosis patients used in the paper.

  Dataset EGAD50000001237

• Hematological toxicity following CAR-T cells injection dataset

  This dataset containes 44 paired of bulk RNA sequencing and 42 parired of single cell RNA sequencing issued from bone marrow aspirations obtained from patients treated with CAR-T (CD3+, CAR T+, CD34+ sorted populations).

  Dataset EGAD50000001142

• Integrated Multiomics Uncovers Distinct Macrophage Alterations in Human Metabolic dysfunction-Associated Steatohepatitis Progression

  We report single-nuclei RNA sequencing data from human livers in metabolic dysfunction-associated steatotic liver disease (MASLD) patients.

  Study EGAS50000000768

• Vascularized human retinal organoids

  Single cell RNA sequencing of human retinal organoids that have been vascularized. Assesses the impact of vascularization on cell types and their gene expression.

  Study EGAS50000000828

• Single-nucleus transcriptome sequencing of the human motor cortex

  Single-nucleus RNA-sequencing of the human motor cortex in patients with ALS, C9ORF72-ALS-FTD, ALS-FTD and unaffected controls.

  Study EGAS50000001562

• Single-cell RNA-sequencing of nivolumab-treated glioblastoma

  Single-cell RNA-sequencing of 8 patients, from primary and relapse tumour (total of 16 samples). Patients were treated with nivolumab prior to relapse surgery.

  Dataset EGAD00001010843

• Bulk RNA-sequencing of nivolumab-treated glioblastoma

  Bulk RNA-sequencing of 30 relapse tumour samples. 20 patients were treated with nivolumab prior to relapse surgery, while 10 patients are control patients.

  Dataset EGAD00001010844

• Single-cell RNA sequencing of RCC patients

  Single-cell RNA sequencing was performed on viable frozen tumor dissociated cells from three RCC patients. The raw data is available as fastq files.

  Dataset EGAD00001011045

• Clear cell sarcoma dataset

  This deposit consists of DNA and RNA sequencing data from 67 CCS samples. 55 samples had tumor DNA sequencing data. 6 had matched normal sequencing data. 34 samples had tumor RNA sequencing data.

  Dataset EGAD00001008611

• RNA sequencing upon depletion of RAF kinases vs. MAPK inhibition in KRAS mutant cells

  RNA Sequencing upon shRNA mediated depletion of RAF kinases or treatment with Cobimetinib (GDC-0973, 250nM, 6hrs) or with pan RAFi (AZ-628, 10uM, 6hrs)

  Dataset EGAD00001008384

• RNA data of neuroblastoma patients

  94 sample with multi-omics analysis of ALT-positive neuroblastoma tumors, rna sequencing

  Dataset EGAD00001006587