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https://www.readbyqxmd.com/read/27929140/acfs-accurate-circrna-identification-and-quantification-from-rna-seq-data
#1
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
#2
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
#3
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...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27856253/discovery-of-high-affinity-bcl6-binding-peptide-and-its-structure-activity-relationship
#4
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...
November 14, 2016: 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
#5
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)...
November 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27843590/ntrk-gene-fusions-as-novel-targets-of-cancer-therapy-across-multiple-tumour-types
#6
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
#7
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
https://www.readbyqxmd.com/read/27485475/identifying-fusion-transcripts-using-next-generation-sequencing
#8
REVIEW
Shailesh Kumar, Sundus Khalid Razzaq, Angie Duy Vo, Mamta Gautam, Hui Li
Fusion transcripts (i.e., chimeric RNAs) resulting from gene fusions have been used successfully for cancer diagnosis, prognosis, and therapeutic applications. In addition, many fusion transcripts are found in normal human cell lines and tissues, with some data supporting their role in normal physiology. Besides chromosomal rearrangement, intergenic splicing can generate them. Global identification of fusion transcripts becomes possible with the help of next generation sequencing technology like RNA-Seq. In the past decade, major advancements have been made for chimeric RNA discovery due to the development of advanced sequencing platform and software packages...
November 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27417935/rewiring-riboswitches-to-create-new-genetic-circuits-in-bacteria
#9
C J Robinson, D Medina-Stacey, M-C Wu, H A Vincent, J Micklefield
Riboswitches are RNA elements that control the expression of genes through a variety of mechanisms in response to the specific binding of small-molecule ligands. Since their discovery, riboswitches have shown promise for the artificial control of transcription or translation of target genes, be it for industrial biotechnology, protein expression, metabolic engineering, antimicrobial target validation, or gene function discovery. However, natural riboswitches are often unsuitable for these purposes due to their regulation by small molecules which are already present within the cell...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/27416267/the-protein-domains-of-the-dictyostelium-microprocessor-that-are-required-for-correct-subcellular-localization-and-for-microrna-maturation
#10
Janis Kruse, Doreen Meier, Fides Zenk, Maren Rehders, Wolfgang Nellen, Christian Hammann
The maturation pathways of microRNAs (miRNAs) have been delineated for plants and several animals, belonging to the evolutionary supergroups of Archaeplastida and Opisthokonta, respectively. Recently, we reported the discovery of the microprocessor complex in Dictyostelium discoideum of the Amoebozoa supergroup. The complex is composed of the Dicer DrnB and the dsRBD (double-stranded RNA binding domain) containing protein RbdB. Both proteins localize at nucleoli, where they physically interact, and both are required for miRNA maturation...
July 14, 2016: RNA Biology
https://www.readbyqxmd.com/read/27259011/recurrent-ntrk1-gene-fusions-define-a-novel-subset-of-locally-aggressive-lipofibromatosis-like-neural-tumors
#11
Narasimhan P Agaram, Lei Zhang, Yun-Shao Sung, Chun-Liang Chen, Catherine T Chung, Cristina R Antonescu, Christopher Dm Fletcher
The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation...
October 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27233447/a-cellular-high-throughput-screening-approach-for-therapeutic-trans-cleaving-ribozymes-and-rnai-against-arbitrary-mrna-disease-targets
#12
Edwin H Yau, Mark C Butler, Jack M Sullivan
Major bottlenecks in development of therapeutic post transcriptional gene silencing (PTGS) agents (e.g. ribozymes, RNA interference, antisense) include the challenge of mapping rare accessible regions of the mRNA target that are open for annealing and cleavage, testing and optimization of agents in human cells to identify lead agents, testing for cellular toxicity, and preclinical evaluation in appropriate animal models of disease. Methods for rapid and reliable cellular testing of PTGS agents are needed to identify potent lead candidates for optimization...
October 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/27191707/exploiting-mitochondria-as-targets-for-the-development-of-new-antifungals
#13
Dongmei Li, Richard Calderone
Mitochondria are essential for cell growth and survival of most fungal pathogens. Energy (ATP) produced during oxidation/reduction reactions of the electron transport cycle (ETC) Complexes I, III and IV (CI, CIII, CIV) fuel cell synthesis. The mitochondria of fungal pathogens are understudied even though more recent published data suggest critical functional assignments to fungal-specific proteins. Proteins of mammalian mitochondria are grouped into 16 functional categories. In this review, we focus upon 11 proteins from five of these categories in fungal pathogens, OXPHOS, protein import, stress response, carbon source metabolism, and fission/fusion morphology...
May 18, 2016: Virulence
https://www.readbyqxmd.com/read/27151993/rna-sequencing-unravels-the-genetics-of-refractory-relapsed-t-cell-acute-lymphoblastic-leukemia-prognostic-and-therapeutic-implications
#14
Valentina Gianfelici, Sabina Chiaretti, Sofie Demeyer, Filomena Di Giacomo, Monica Messina, Roberta La Starza, Nadia Peragine, Francesca Paoloni, Ellen Geerdens, Valentina Pierini, Loredana Elia, Marco Mancini, Maria Stefania De Propris, Valerio Apicella, Gianluca Gaidano, Anna Maria Testi, Antonella Vitale, Marco Vignetti, Cristina Mecucci, Anna Guarini, Jan Cools, Robin FoĆ 
Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases...
August 2016: Haematologica
https://www.readbyqxmd.com/read/26957201/hiv-1-capsid-inhibitors-as-antiretroviral-agents
#15
Suzie Thenin-Houssier, Susana T Valente
BACKGROUND: The infectious human immunodeficiency virus (HIV) particle is characterized by a conical capsid that encloses the viral RNA genome. The capsid is essential for HIV-1 replication and plays crucial roles in both early and late stages of the viral life cycle. Early on, upon fusion of the viral and cellular membranes, the viral capsid is released into the host cell cytoplasm and dissociates in a process known as uncoating, tightly associated with the reverse transcription of the viral genome...
2016: Current HIV Research
https://www.readbyqxmd.com/read/26883001/molecular-features-of-cellular-reprogramming-and-development
#16
REVIEW
Zachary D Smith, Camille Sindhu, Alexander Meissner
Differentiating somatic cells are progressively restricted to specialized functions during ontogeny, but they can be experimentally directed to form other cell types, including those with complete embryonic potential. Early nuclear reprogramming methods, such as somatic cell nuclear transfer (SCNT) and cell fusion, posed significant technical hurdles to precise dissection of the regulatory programmes governing cell identity. However, the discovery of reprogramming by ectopic expression of a defined set of transcription factors, known as direct reprogramming, provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability and pluripotency...
March 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/26871368/fusion-genes-in-malignant-neoplastic-disorders-of-haematopoietic-system
#17
Mohamed Saleem, Narazah Mohd Yusoff
OBJECTIVES: The new World Health Organization's (WHO) classification of haematopoietic and lymphoid tissue neoplasms incorporating the recurrent fusion genes as the defining criteria for different haematopoietic malignant phenotypes is reviewed. The recurrent fusion genes incorporated in the new WHO's classification and other chromosomal rearrangements of haematopoietic and lymphoid tissue neoplasms are reviewed. METHODOLOGY: Cytokines and transcription factors in haematopoiesis and leukaemic mechanisms are described...
October 2016: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/26867494/novel-pre-mrna-splicing-of-intronically-integrated-hbv-generates-oncogenic-chimera-in-hepatocellular-carcinoma
#18
Yung-Tuen Chiu, John K L Wong, Shing-Wan Choi, Karen M F Sze, Daniel W H Ho, Lo-Kong Chan, Joyce M F Lee, Kwan Man, Stacey Cherny, Wan-Ling Yang, Chun-Ming Wong, Pak-Chung Sham, Irene O L Ng
BACKGROUND & AIMS: Hepatitis B virus (HBV) integration is common in HBV-associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs. METHODS: Transcriptome sequencing was performed on paired HBV-associated HCCs and corresponding non-tumorous liver tissues to identify viral-human chimeric sites. Validation was further performed in an expanded cohort of human HCCs...
June 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/26862001/comparative-assessment-of-methods-for-the-fusion-transcripts-detection-from-rna-seq-data
#19
Shailesh Kumar, Angie Duy Vo, Fujun Qin, Hui Li
RNA-Seq made possible the global identification of fusion transcripts, i.e. "chimeric RNAs". Even though various software packages have been developed to serve this purpose, they behave differently in different datasets provided by different developers. It is important for both users, and developers to have an unbiased assessment of the performance of existing fusion detection tools. Toward this goal, we compared the performance of 12 well-known fusion detection software packages. We evaluated the sensitivity, false discovery rate, computing time, and memory usage of these tools in four different datasets (positive, negative, mixed, and test)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26812183/a-high-performance-platform-based-on-cdna-display-for-efficient-synthesis-of-protein-fusions-and-accelerated-directed-evolution
#20
Mohammed Naimuddin, Tai Kubo
We describe a high performance platform based on cDNA display technology by developing a new modified puromycin linker-oligonucleotide. The linker consists of four major characteristics: a "ligation site" for hybridization and ligation of mRNA by T4 RNA ligase, a "puromycin arm" for covalent linkage of the protein, a "polyadenosine site" for a longer puromycin arm and purification of protein fusions (optional) using oligo-dT matrices, and a "reverse transcription site" for the formation of stable cDNA protein fusions whose cDNA is covalently linked to its encoded protein...
February 8, 2016: ACS Combinatorial Science
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