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fusion transcript discovery

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https://www.readbyqxmd.com/read/28575524/identifying-transposon-insertions-and-their-effects-from-rna-sequencing-data
#1
Julian R de Ruiter, Sjors M Kas, Eva Schut, David J Adams, Marco J Koudijs, Lodewyk F A Wessels, Jos Jonkers
Insertional mutagenesis using engineered transposons is a potent forward genetic screening technique used to identify cancer genes in mouse model systems. In the analysis of these screens, transposon insertion sites are typically identified by targeted DNA-sequencing and subsequently assigned to predicted target genes using heuristics. As such, these approaches provide no direct evidence that insertions actually affect their predicted targets or how transcripts of these genes are affected. To address this, we developed IM-Fusion, an approach that identifies insertion sites from gene-transposon fusions in standard single- and paired-end RNA-sequencing data...
June 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28525538/chimeraviz-a-tool-for-visualizing-chimeric-rna
#2
Stian Lågstad, Sen Zhao, Andreas M Hoff, Bjarne Johannessen, Ole Christian Lingjærde, Rolf I Skotheim
Summary: Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for fusion detection from sequencing data often yield a high false discovery rate. Good prioritization of the results is important, and this can be helped by a visualization framework that automatically integrates RNA data with known genomic features. Here we present chimeraviz , a Bioconductor package that automates the creation of chimeric RNA visualizations...
May 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28489570/transcriptome-profiling-identifies-a-recurrent-cryl1-ift88-chimeric-transcript-in-hepatocellular-carcinoma
#3
Yi Huang, Jiaying Zheng, Dunyan Chen, Feng Li, Wenbing Wu, Xiaoli Huang, Yanan Wu, Yangyang Deng, Funan Qiu
We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways including cell cycle, DNA replication, p53, complement and coagulation cascades, etc. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#4
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28380446/identification-of-kansarl-as-the-first-cancer-predisposition-fusion-gene-specific-to-the-population-of-european-ancestry-origin
#5
Jeff Xiwu Zhou, Xiaoyan Yang, Shunbin Ning, Ling Wang, Kesheng Wang, Yanbin Zhang, Fenghua Yuan, Fengli Li, David D Zhuo, Liren Tang, Degen Zhuo
Gene fusion is one of the hallmarks of cancer. Recent advances in RNA-seq of cancer transcriptomes have facilitated the discovery of fusion transcripts. In this study, we report identification of a surprisingly large number of fusion transcripts, including six KANSARL (KANSL1-ARL17A) transcripts that resulted from the fusion between the KANSL1 and ARL17A genes using a RNA splicingcode model. Five of these six KANSARL fusion transcripts are novel. By systematic analysis of RNA-seq data of glioblastoma, prostate cancer, lung cancer, breast cancer, and lymphoma from different regions of the World, we have found that KANSARL fusion transcripts were rarely detected in the tumors of individuals from Asia or Africa...
March 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28358915/enhancement-of-arabidopsis-growth-characteristics-using-genome-interrogation-with-artificial-transcription-factors
#6
Niels van Tol, Martijn Rolloos, Johan E Pinas, Christiaan V Henkel, Dieuwertje Augustijn, Paul J J Hooykaas, Bert J van der Zaal
The rapidly growing world population has a greatly increasing demand for plant biomass, thus creating a great interest in the development of methods to enhance the growth and biomass accumulation of crop species. In this study, we used zinc finger artificial transcription factor (ZF-ATF)-mediated genome interrogation to manipulate the growth characteristics and biomass of Arabidopsis plants. We describe the construction of two collections of Arabidopsis lines expressing fusions of three zinc fingers (3F) to the transcriptional repressor motif EAR (3F-EAR) or the transcriptional activator VP16 (3F-VP16), and the characterization of their growth characteristics...
2017: PloS One
https://www.readbyqxmd.com/read/28352191/retinoic-acid-and-arsenic-trioxide-in-the-treatment-of-acute-promyelocytic-leukemia-current-perspectives
#7
REVIEW
Derek McCulloch, Christina Brown, Harry Iland
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28299659/mechanism-of-etv6-runx1-leukemia
#8
Aishwarya Sundaresh, Owen Williams
The t(12;21)(p13;q22) translocation is the most frequently occurring single genetic abnormality in pediatric leukemia. This translocation results in the fusion of the ETV6 and RUNX1 genes. Since its discovery in the 1990s, the function of the ETV6-RUNX1 fusion gene has attracted intense interest. In this chapter, we will summarize current knowledge on the clinical significance of ETV6-RUNX1, the experimental models used to unravel its function in leukemogenesis, the identification of co-operating mutations and the mechanisms responsible for their acquisition, the function of the encoded transcription factor and finally, the future therapeutic approaches available to mitigate the associated disease...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299648/structure-and-biophysics-of-cbf%C3%AE-runx-and-its-translocation-products
#9
Tahir H Tahirov, John Bushweller
The core binding factor (CBF) transcription factor is somewhat unique in that it is composed of a DNA binding RUNX subunit (RUNX1, 2, or 3) and a non-DNA binding CBFβ subunit, which modulates RUNX protein activity by modulating the auto-inhibition of the RUNX subunits. Since the discovery of this fascinating transcription factor more than 20 years ago, there has been a robust effort to characterize the structure as well as the biochemical properties of CBF. More recently, these efforts have also extended to the fusion proteins that arise from the subunits of CBF in leukemia...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28261265/new-insights-into-transcriptional-and-leukemogenic-mechanisms-of-aml1-eto-and-e2a-fusion-proteins
#10
Jian Li, Chun Guo, Nickolas Steinauer, Jinsong Zhang
BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28240214/genomic-alterations-of-non-coding-regions-underlie-human-cancer-lessons-from-t-all
#11
REVIEW
Adrian Rivera-Reyes, Katharina E Hayer, Craig H Bassing
It has been appreciated for decades that somatic genomic alterations that change coding sequences of proto-oncogenes, translocate enhancers/promoters near proto-oncogenes, or create fusion oncogenes can drive cancer by inducing oncogenic activities. An explosion of genome-wide technologies over the past decade has fueled discoveries of the roles of three-dimensional chromosome structure and powerful cis-acting elements (super-enhancers) in regulating gene transcription. In recent years, studies of human T cell acute lymphoblastic leukemia (T-ALL) using genome-wide technologies have provided paradigms for how non-coding genomic region alterations can disrupt 3D chromosome architecture or establish super-enhancers to activate oncogenic transcription of proto-oncogenes...
December 2016: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28185541/kaos-a-new-automated-computational-method-for-the-identification-of-overexpressed-genes
#12
Angelo Nuzzo, Giovanni Carapezza, Sebastiano Di Bella, Alfredo Pulvirenti, Antonella Isacchi, Roberta Bosotti
BACKGROUND: Kinase over-expression and activation as a consequence of gene amplification or gene fusion events is a well-known mechanism of tumorigenesis. The search for novel rearrangements of kinases or other druggable genes may contribute to understanding the biology of cancerogenesis, as well as lead to the identification of new candidate targets for drug discovery. However this requires the ability to query large datasets to identify rare events occurring in very small fractions (1-3 %) of different tumor subtypes...
November 8, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28114882/fugeprior-a-novel-gene-fusion-prioritization-algorithm-based-on-accurate-fusion-structure-analysis-in-cancer-rna-seq-samples
#13
Giulia Paciello, Elisa Ficarra
BACKGROUND: Latest Next Generation Sequencing technologies opened the way to a novel era of genomic studies, allowing to gain novel insights into multifactorial pathologies as cancer. In particular gene fusion detection and comprehension have been deeply enhanced by these methods. However, state of the art algorithms for gene fusion identification are still challenging. Indeed, they identify huge amounts of poorly overlapping candidates and all the reported fusions should be considered for in lab validation clearly overwhelming wet lab capabilities...
January 23, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/27929140/acfs-accurate-circrna-identification-and-quantification-from-rna-seq-data
#14
Xintian You, Tim Of Conrad
Circular RNAs (circRNAs) are a group of single-stranded RNAs in closed circular form. They are splicing-generated, widely expressed in various tissues and have functional implications in development and diseases. To facilitate genome-wide characterization of circRNAs using RNA-Seq data, we present a freely available software package named acfs. Acfs allows de novo, accurate and fast identification and abundance quantification of circRNAs from single- and paired-ended RNA-Seq data. On simulated datasets, acfs achieved the highest F1 accuracy and lowest false discovery rate among current state-of-the-art tools...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907167/infusion-advancing-discovery-of-fusion-genes-and-chimeric-transcripts-from-deep-rna-sequencing-data
#15
Konstantin Okonechnikov, Aki Imai-Matsushima, Lukas Paul, Alexander Seitz, Thomas F Meyer, Fernando Garcia-Alcalde
Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found...
2016: PloS One
https://www.readbyqxmd.com/read/27899596/chitars-3-1-the-enhanced-chimeric-transcripts-and-rna-seq-database-matched-with-protein-protein-interactions
#16
Alessandro Gorohovski, Somnath Tagore, Vikrant Palande, Assaf Malka, Dorith Raviv-Shay, Milana Frenkel-Morgenstern
Discovery of chimeric RNAs, which are produced by chromosomal translocations as well as the joining of exons from different genes by trans-splicing, has added a new level of complexity to our study and understanding of the transcriptome. The enhanced ChiTaRS-3.1 database (http://chitars.md.biu.ac.il) is designed to make widely accessible a wealth of mined data on chimeric RNAs, with easy-to-use analytical tools built-in. The database comprises 34 922: chimeric transcripts along with 11 714: cancer breakpoints...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27856253/discovery-of-high-affinity-bcl6-binding-peptide-and-its-structure-activity-relationship
#17
Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Nozomu Sakai, Kouhei Asano, Mie Yoshimatsu, Kou Ida, Yasuhiro Imaeda, Jun-Ichi Sakamoto
B cell lymphoma 6 (BCL6) is a transcriptional repressor that interacts with its corepressors BcoR and SMRT. Since this protein-protein interaction (PPI) induces activation and differentiation of B lymphocytes, BCL6 has been an attractive drug target for potential autoimmune disease treatments. Here we report a novel BCL6 inhibitory peptide, F1324 (Ac-LWYTDIRMSWRVP-OH), which we discovered using phage display technology; we also discuss this peptide's structure-activity relationship (SAR). For BCL6(5-129) binding, KD and IC50 values of F1324 were 0...
January 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27855558/diagnostic-evaluation-of-rna-sequencing-for-the-detection-of-genetic-abnormalities-associated-with-ph-like-acute-lymphoblastic-leukemia-all
#18
Kai Lee Yap, Larissa V Furtado, Kazuma Kiyotani, Emily Curran, Wendy Stock, Jennifer L McNeer, Sabah Kadri, Jeremy P Segal, Yusuke Nakamura, Michelle M Le Beau, Sandeep Gurbuxani, Gordana Raca
Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a molecular subtype of high-risk B-cell ALL characterized by formation of abnormal gene fusions involving tyrosine kinase (TK) and cytokine receptor genes and activation of TK signaling. Because of the diversity of associated genetic changes, the detection of Ph-like ALL cases currently requires multiple cytogenetic and molecular assays; thus, our goal was to develop a consolidated workflow for detecting genetic abnormalities in Ph-like ALL. We found that total and targeted RNA sequencing (RNAseq)-based approach allowed the detection of abnormal fusion transcripts (EBF1-PDGFRB, P2RY8-CRLF2, RCSD1-ABL1, and RCSD1-ABL2)...
April 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27843590/ntrk-gene-fusions-as-novel-targets-of-cancer-therapy-across-multiple-tumour-types
#19
REVIEW
Alessio Amatu, Andrea Sartore-Bianchi, Salvatore Siena
The tropomyosin receptor kinase (Trk) receptor family comprises 3 transmembrane proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors that are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue and play an essential role in the physiology of development and function of the nervous system through activation by neurotrophins. Gene fusions involving NTRK genes lead to transcription of chimeric Trk proteins with constitutively activated or overexpressed kinase function conferring oncogenic potential...
2016: ESMO Open
https://www.readbyqxmd.com/read/27662880/targeted-gene-activation-using-rna-guided-nucleases
#20
Alexander Brown, Wendy S Woods, Pablo Perez-Pinera
The discovery of the prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) system and its adaptation for targeted manipulation of DNA in diverse species has revolutionized the field of genome engineering. In particular, the fusion of catalytically inactive Cas9 to any number of transcriptional activator domains has resulted in an array of easily customizable synthetic transcription factors that are capable of achieving robust, specific, and tunable activation of target gene expression within a wide variety of tissues and cells...
2017: Methods in Molecular Biology
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