CREST: an algorithm that directly maps structural variants for next-generation sequencing data
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PROVIDER: PRJNA75297 | ENA |
REPOSITORIES: ENA
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Project description:CREST: an algorithm that directly maps structural variants for next-generation sequencing data
| PRJNA75299 | ENA
Project description:Structural variants can lead to an alteration of gene expression which may be associated with disease worsening. In our study we attempted to describe expression changes associated with the presence of extensive genomic rearrangements in chronic lymphocytic leukemia. We used microarrays for establishing an algorithm for identification of unique expression profiles associated with extensive genomic rearrangements.
2019-05-13 | GSE124329 | GEO
Project description:Aminoglycosides resistance mechanisms inference algorithm
| PRJEB29576 | ENA
Project description:We developed a novel algorithm, smORFer, detecting smORFs (e.g. <50 codons) which performs with higher accuracy in prokaryotic organisms. smORFer considers structural features of genetic sequence along with in-register translation and using Fourier transform converts them into a measurable score to faithfully select smORFs. The algorithm is executed in a modular way and dependent on the data available different modules can be tested.
2021-05-12 | GSE150601 | GEO
Project description:Structural characterization of ribosome variants
| PRJNA414663 | ENA
Project description:We developed 'clipping reveals structure' (CREST), an algorithm that uses next-generation sequencing reads with partial alignments to a reference genome to directly map structural variations at the nucleotide level of resolution. Application of CREST to whole-genome sequencing data from five pediatric T-lineage acute lymphoblastic leukemias (T-ALLs) and a human melanoma cell line, COLO-829, identified 160 somatic structural variations. Experimental validation exceeded 80%, demonstrating that CREST had a high predictive accuracy.
| S-EPMC3527068 | biostudies-literature
Project description:<p><b>CREST</b></p> <p>The accurate identification of structural variations using whole-genome DNA sequencing data generated by next-generation sequencing technology is extremely difficult. To address this challenge, we have developed CREST, an algorithm that uses sequencing reads with partial alignments to the reference human genome (so-called soft-clipped reads) to directly map the breakpoints of somatic structural variations. We applied CREST to paired tumor/normal whole genome sequencing data from five cases of T-lineage acute lymphoblastic leukemia (T-ALL). A total of 110 somatic structural variants were identified, >80% of which were validated by genomic PCR and Sanger sequencing. The validated structural variants included 31 inter-chromosomal translocations, 19 intra-chromosomal translocations, one inversion, 22 deletions and 16 insertions. A comparison of the results generated with CREST to those obtained using the traditional paired-end discordant mapping methods demonstrate CREST to have a much higher sensitivity and specificity. In addition, application of CREST to publicly available whole-genome sequencing data from the human melanoma cancer cell line COLO-829 demonstrated the identification of 50 novel structural variations not detected using the standard methods, 20 of which were selected for validation with a 90% success rate. These data demonstrate that direct mapping of soft-clipped reads offers an improved method for detecting structural variants at the nucleotide level of resolution.</p> <p><b>T-ALL</b></p> <p>Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; <i>NRAS</i>, <i>KRAS</i>, <i>FLT3</i>, <i>IL7R</i>, <i>JAK3</i>, <i>JAK1</i>, <i>SH2B3</i> and <i>BRAF</i>), inactivating lesions disrupting haematopoietic development (58%; <i>GATA3</i>, <i>ETV6</i>, <i>RUNX1</i>, <i>IKZF1</i> and <i>EP300</i>) and histone-modifying genes (48%; <i>EZH2</i>, <i>EED</i>, <i>SUZ12</i>, <i>SETD2</i> and <i>EP300</i>). We also identified new targets of recurrent mutation including <i>DNM2</i>, <i>ECT2L</i> and <i>RELN</i>. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.</p>
| phs000340 | dbGaP
Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.
2022-10-04 | GSE147123 | GEO
Project description:We utilized quantitative analyses of the proteome, transcriptome, and ubiquitinome to study how ubiquitination and NEDD4 control neural crest cell survival and stem-cell-like properties. We report 276 novel NEDD4 targets in neural crest cells and show that loss of NEDD4 leads to a striking global reduction in specific ubiquitin lysine linkages.
2022-02-08 | PXD024103 | Pride
Project description:Pathogenic Structural Variants in Leukemia Genomes
| PRJEB50975 | ENA