Integrative analysis of non-coding variants in human leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA566156 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10138130.fastq.gz | Fastqsanger.gz | |||
| SRR10138131.fastq.gz | Fastqsanger.gz | |||
| SRR10138132.fastq.gz | Fastqsanger.gz | |||
| SRR10138133.fastq.gz | Fastqsanger.gz | |||
| SRR10138134.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 133 |
Similar Datasets
Project description:Integrative analysis of genomic structural variants in human leukemia
| PRJNA821195 | ENA
Project description:Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements (CREs), contribute to cancer pathophysiology. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage-specific CREs and mutation discovery, and uncovered 1,837 recurrently mutated CREs containing leukemia-associated non-coding variants. By enhanced CRISPR/dCas9-based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor suppressive CREs in human leukemia. Non-coding variants at KRAS and PER2 enhancers reside in nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in situ in leukemia cells. NR binding sites frequently co-localize with non-coding variants across cancer types. Hence, recurrent non-coding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.
2020-04-22 | GSE137652 | GEO
Project description:Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements (CREs), contribute to cancer pathophysiology. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants with functional consequences in human hematopoietic malignancies. Combining targeted resequencing of hematopoietic lineage-specific CREs and mutation discovery, and uncovered 1,837 recurrently mutated CREs containing leukemia-associated non-coding variants. By enhanced CRISPR/dCas9-based CRE perturbation screening and functional analyses, we identified 218 variant-associated oncogenic or tumor suppressive CREs in human leukemia. Non-coding variants at KRAS and PER2 enhancers reside in nuclear receptor (NR) binding regions and modulate transcriptional activities in response to NR signaling in situ in leukemia cells. NR binding sites frequently co-localize with non-coding variants across cancer types. Hence, recurrent non-coding variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.
2020-04-22 | GSE137647 | GEO
Project description:We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants. RNA-Sequencing of CEPH/UTAH family 1463
2014-09-01 | E-GEOD-56961 | biostudies-arrayexpress
Project description:We have combined high-quality genome sequencing and RNA-sequencing data within a 17-individual, three generation family. Using these data, we have contrasted cis-acting expression, allele-specific expression and splicing quantitative trait loci (collectively termed eQTLs) within the family to eQTLs discovered within a cell-type and ethnicity-matched population sample. We identified that eQTL that exhibit larger effects in the family compared to the population are enriched for rare regulatory and splicing variants and were more likely to influence essential genes. In addition, we identify several large effect-size eQTLs within the family for genes involved in complex disease. Through analysis of eQTLs in a large family we also report the utility of non-coding genome annotation to predicting the effect of rare non-coding variants. We find that a combination of distance to the transcription start site, evolutionary constraint and epigenetic annotation is considerably more informative for predicting the consequence of rare non-coding variants than for common variants. In summary, through transcriptome analyses within a large family we are able to identify the contribution of rare non-coding variants to expression phenotypes and further demonstrate the predictive potential of diverse non-coding genome annotation for interpretation of the impact of rare non-coding variants.
2014-09-01 | GSE56961 | GEO
Project description:A number of genetic studies have identified rare protein-coding DNA variations associated with autism spectrum disorder (ASD), a neurodevelopmental disorder with significant genetic etiology and heterogeneity. In contrast, the contributions of functional, regulatory genetic variations that occur in the extensive non-protein-coding regions of the genome remain poorly understood. Here we developed a genome-wide analysis to identify rare single nucleotide variants (SNVs) that occur in non-coding regions and determined regulatory function and evolutionary conservation of these variants. Using publicly available datasets and computational predictions, we identified SNVs within putative regulatory regions in promoters, transcription factor binding sites, microRNA genes and their target sites. Overall, we found regulatory variants in the ASD cases were enriched in autism-risk genes and genes involved in fetal neurodevelopment. As with previously reported coding mutations, we found an enrichment of regulatory variants associated with dysregulation of neurodevelopmental and synaptic signaling pathways. Among these were rare inherited non-coding SNVs found in the mature sequence of a number of microRNAs predicted to affect the regulation of autism-risk genes. We show a paternally inherited miR-873-5p variant, with reduced NRXN2 binding affinity, overlays a maternally inherited NRXN1 putative loss-of-function coding variation to likely increase genetic liability in an idiopathic ASD case. Our analysis pipeline provides a new resource for identifying loss-of-function regulatory DNA variations that may contribute to the genetic etiology of complex disorders.
2017-04-25 | GSE98088 | GEO
Project description:Glucocorticoids Unmask Silent Non-Coding Genetic Risk Variants for Common Diseases
| PRJNA771402 | ENA
Project description:Identification of Atrial Fibrillation associated genes and functional non-coding variants
| PRJNA525655 | ENA
Project description:Massively parallel functional dissection of schizophrenia associated non-coding genetic variants
| PRJNA937652 | ENA
Project description:Mutations in protein-coding genes are well established as the basis for human cancer, yet it remains elusive how alterations within non-coding genome, a substantial fraction of which contain cis-regulatory elements, contribute to cancer pathophysiology largely due to lack of high throughput assays to assess their functional effects. Here we developed an integrative approach to systematically identify and characterize non-coding regulatory variants in human hematopoietic malignancies by combining targeted resequencing, mutation discovery, CRISPR-based enhancer-selective epigenome editing, and enhancer reporter assays. We identify 4,629 recurrent non-coding alterations and 939 mutation-associated pathogenic enhancers controlling proto-oncogenes or tumor suppressors. Enhancer variants at KRAS and PER2 co-localize with nuclear receptor (NR) binding sites and modulate transcriptional activities in response to NR signaling in leukemia cells. NR binding sites frequently associate with non-coding variants across cancer types. Hence, recurrent non-coding somatic variants connect enhancer dysregulation with nuclear receptor signaling in hematopoietic malignancies.
2020-04-22 | GSE125939 | GEO