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fusion transcript discovery

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https://www.readbyqxmd.com/read/29754229/designed-transcriptional-regulation-in-mammalian-cells-based-on-tale-and-crispr-dcas9
#1
Tina Lebar, Roman Jerala
Transcriptional regulation lies at the center of many cellular processes and is the result of cellular response to different external and internal signals. Control of transcription of selected genes enables an unprecedented access to shape the cellular response. While orthogonal transcription factors from bacteria, yeast, plants, or other cells have been used to introduce new cellular logic into mammalian cells, the discovery of designable modular DNA binding domains, such as Transcription Activator-Like Effectors (TALEs) and the CRISPR system, enable targeting of almost any selected DNA sequence...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29534934/discovery-of-potent-dot1l-inhibitors-by-alphalisa-based-high-throughput-screening-assay
#2
Yakai Song, Linjuan Li, Yantao Chen, Jingqiu Liu, Senhao Xiao, Fulin Lian, Naixia Zhang, Hong Ding, Yuanyuan Zhang, Kaixian Chen, Hualiang Jiang, Chenhua Zhang, Yu-Chih Liu, Shijie Chen, Cheng Luo
DOT1L (the disruptor of telomeric silencing 1-like), through its methyltransferase activity of H3K79, plays essential roles in transcriptional regulation, cell cycle regulation, and DNA damage response. In addition, DOT1L is believed to be involved in the development of MLL-rearranged leukemia driven by the MLL (mixed-lineage leukemia) fusion proteins, which thus to be a crucial target for leukemia therapy. Hence, discovering of novel DOT1L inhibitors has been in a great demand. In this study, we initiated the discovering process from setting up the AlphaLISA based High Throughput Screening (HTS) assay of DOT1L...
May 1, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29474638/star-chimeric-post-for-rapid-detection-of-circular-rna-and-fusion-transcripts
#3
Nicholas K Akers, Eric E Schadt, Bojan Losic
Motivation: The biological relevance of chimeric RNA alignments is now well established. Chimera arising as chromosomal fusions are often drivers of cancer, and recently discovered circular RNA are only now being characterized. While software already exists for fusion discovery and quantitation, high false positive rates and high run-times hamper scalable fusion discovery on large datasets. Furthermore, software available for circular RNA detection and quantification is limited. Results: Here we present STAR Chimeric Post (STARChip), a novel software package that processes chimeric alignments from the STAR aligner and produces annotated circular RNA and high precision fusions in a rapid, efficient, and scalable manner that is appropriate for high dimensional medical omics datasets...
February 20, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29414922/perspective-insight-into-future-potential-fusion-gene-transcript-biomarker-candidates-in-breast-cancer
#4
REVIEW
Ryong Nam Kim, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh
Next generation sequencing has accelerated the discovery of a variety of new fusion gene types in clinical breast cancer samples by analyzing cancer genomes and transcriptomes. Although previous studies have focused on a few clinically validated oncogenic fusion genes as diagnostic and therapeutic targets in breast cancer, a perspective consideration has not been given thus far for a plethora of breast cancer fusion genes, which are being newly identified at an overwhelmingly increasing pace. In this perspective review, we discuss diverse fusion gene types recently identified in a variety of breast cancer subtypes, including breast clinical cancer samples in TCGA (The Cancer Genome Atlas) database...
February 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29382099/in-silico-and-in-vitro-guided-identification-of-inhibitors-of-alkylquinolone-dependent-quorum-sensing-in-pseudomonas-aeruginosa
#5
Fadi Soukarieh, Eduard Vico Oton, Jean-Frédéric Dubern, Janice Gomes, Nigel Halliday, Maria de Pilar Crespo, Jonathan Ramírez-Prada, Braulio Insuasty, Rodrigo Abonia, Jairo Quiroga, Stephan Heeb, Paul Williams, Michael J Stocks, Miguel Cámara
Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System ( pqs ) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29346292/isoform-sequencing-and-state-of-art-applications-for-unravelling-complexity-of-plant-transcriptomes
#6
REVIEW
Dong An, Hieu X Cao, Changsheng Li, Klaus Humbeck, Wenqin Wang
Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications...
January 18, 2018: Genes
https://www.readbyqxmd.com/read/29258295/therapeutic-targeting-of-ependymoma-as-informed-by-oncogenic-enhancer-profiling
#7
Stephen C Mack, Kristian W Pajtler, Lukas Chavez, Konstantin Okonechnikov, Kelsey C Bertrand, Xiuxing Wang, Serap Erkek, Alexander Federation, Anne Song, Christine Lee, Xin Wang, Laura McDonald, James J Morrow, Alina Saiakhova, Patrick Sin-Chan, Qiulian Wu, Kulandaimanuvel Antony Michaelraj, Tyler E Miller, Christopher G Hubert, Marina Ryzhova, Livia Garzia, Laura Donovan, Stephen Dombrowski, Daniel C Factor, Betty Luu, Claudia L L Valentim, Ryan C Gimple, Andrew Morton, Leo Kim, Briana C Prager, John J Y Lee, Xiaochong Wu, Jennifer Zuccaro, Yuan Thompson, Borja L Holgado, Jüri Reimand, Susan Q Ke, Adam Tropper, Sisi Lai, Senthuran Vijayarajah, Sylvia Doan, Vaidehi Mahadev, Ana Fernandez Miñan, Susanne N Gröbner, Matthias Lienhard, Marc Zapatka, Zhiqin Huang, Kenneth D Aldape, Angel M Carcaboso, Peter J Houghton, Stephen T Keir, Till Milde, Hendrik Witt, Yan Li, Chao-Jun Li, Xiu-Wu Bian, David T W Jones, Ian Scott, Sheila K Singh, Annie Huang, Peter B Dirks, Eric Bouffet, James E Bradner, Vijay Ramaswamy, Nada Jabado, James T Rutka, Paul A Northcott, Mathieu Lupien, Peter Lichter, Andrey Korshunov, Peter C Scacheri, Stefan M Pfister, Marcel Kool, Michael D Taylor, Jeremy N Rich
Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy...
January 4, 2018: Nature
https://www.readbyqxmd.com/read/29230372/integrated-downstream-regulation-by-the-quorum-sensing-controlled-transcription-factors-lrha-and-rcsa-impacts-phenotypic-outputs-associated-with-virulence-in-the-phytopathogen-pantoea-stewartii-subsp-stewartii
#8
Duy An Duong, Ann M Stevens
Pantoea stewartii subsp. stewartii is a Gram-negative proteobacterium that causes leaf blight and Stewart's wilt disease in corn. Quorum sensing (QS) controls bacterial exopolysaccharide production that blocks water transport in the plant xylem at high bacterial densities during the later stage of the infection, resulting in wilt. At low cell density the key master QS regulator in P. stewartii , EsaR, directly represses rcsA , encoding an activator of capsule biosynthesis genes, but activates lrhA , encoding a transcription factor that regulates surface motility...
2017: PeerJ
https://www.readbyqxmd.com/read/29075538/an-unsuspected-finding-of-t-9-22-a-rare-case-of-philadelphia-chromosome-positive-b-lymphoblastic-lymphoma
#9
Prajwal Boddu, C Cameron Yin, Rashmi Kanagal-Shamanna, Guillin Tang, Beenu Thakral, Tapan Kadia, Marina Konopleva, Elias Jabbour, Nitin Jain
While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28978704/human-metapneumovirus-induces-formation-of-inclusion-bodies-for-efficient-genome-replication-and-transcription
#10
Nicolás Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch
Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm...
December 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28951853/ironing-out-the-unconventional-mechanisms-of-iron-acquisition-and-gene-regulation-in-chlamydia
#11
REVIEW
Nick D Pokorzynski, Christopher C Thompson, Rey A Carabeo
The obligate intracellular pathogen Chlamydia trachomatis, along with its close species relatives, is known to be strictly dependent upon the availability of iron. Deprivation of iron in vitro induces an aberrant morphological phenotype termed "persistence." This persistent phenotype develops in response to various immunological and nutritional insults and may contribute to the development of sub-acute Chlamydia-associated chronic diseases in susceptible populations. Given the importance of iron to Chlamydia, relatively little is understood about its acquisition and its role in gene regulation in comparison to other iron-dependent bacteria...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28881586/identification-of-kansarl-as-the-first-cancer-predisposition-fusion-gene-specific-to-the-population-of-european-ancestry-origin
#12
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28851811/the-mitf-tfe-family-of-transcription-factors-master-regulators-of-organelle-signaling-metabolism-and-stress-adaptation
#13
REVIEW
Logan Slade, Thomas Pulinilkunnil
The microphthalmia family (MITF, TFEB, TFE3, and TFEC) of transcription factors is emerging as global regulators of cancer cell survival and energy metabolism, both through the promotion of lysosomal genes as well as newly characterized targets, such as oxidative metabolism and the oxidative stress response. In addition, MiT/TFE factors can regulate lysosomal signaling, which includes the mTORC1 and Wnt/β-catenin pathways, which are both substantial contributors to oncogenic signaling. This review describes recent discoveries in MiT/TFE research and how they impact multiple cancer subtypes...
December 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28802831/validation-of-a-targeted-rna-sequencing-assay-for-kinase-fusion-detection-in-solid-tumors
#14
Julie W Reeser, Dorrelyn Martin, Jharna Miya, Esko A Kautto, Ezra Lyon, Eliot Zhu, Michele R Wing, Amy Smith, Matthew Reeder, Eric Samorodnitsky, Hannah Parks, Karan R Naik, Joseph Gozgit, Nicholas Nowacki, Kurtis D Davies, Marileila Varella-Garcia, Lianbo Yu, Aharon G Freud, Joshua Coleman, Dara L Aisner, Sameek Roychowdhury
Kinase gene fusions are important drivers of oncogenic transformation and can be inhibited with targeted therapies. Clinical grade diagnostics using RNA sequencing to detect gene rearrangements in solid tumors are limited, and the few that are available require prior knowledge of fusion break points. To address this, we have analytically validated a targeted RNA sequencing assay (OSU-SpARKFuse) for fusion detection that interrogates complete transcripts from 93 kinase and transcription factor genes. From a total of 74 positive and 36 negative control samples, OSU-SpARKFuse had 93...
September 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28575524/identifying-transposon-insertions-and-their-effects-from-rna-sequencing-data
#15
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...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28525538/chimeraviz-a-tool-for-visualizing-chimeric-rna
#16
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...
September 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28489570/transcriptome-profiling-identifies-a-recurrent-cryl1-ift88-chimeric-transcript-in-hepatocellular-carcinoma
#17
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
#18
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
#19
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
#20
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
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