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作者： Sundfeld, Daniel Teodoro, George Havgaard, Jakob H. Gorodkin, Jan Melo, Alba C. M. A. Information and Communication Technology Brasília Federal Institute Brasília Brazil Department of Computer Science University of Brasília Brasília Brazil Center for Non-Coding RNA in Technology and Health Department of Veterinary and Animal Sciences University of Copenhagen Copenhagen Denmark

Structural alignments of Ribonucleic acid (rna) sequences solved by the Sankoff algorithm are computationally expensive and often require constraints to be used in practice. Modern Graphics Processing Units (GPUs) contain more than 1000 cores, which compute in parallel to speed up applications. Here, we present a GPU-based solution to the rna structural alignment problem that makes use of precalculated base pair probabilities on the individual sequences. We designed and developed an unconstrained version of the Sankoff algorithm, obtaining the optimal result and calculating the entire four-dimension dynamic programming matrix (4D DP). Our approach uses a two-level wavefront strategy to exploit parallelism. The 4D DP matrix is divided in one external matrix (EM) and several internal matrices (IM). We applied wavefront strategies on the EM and IMs in a two-level hierarchical way. At the first level, the wavefront is applied to the EM, calculating the cells that belong to the same diagonal in parallel. In the second level, since each cell in the EM is itself an IM matrix, the cells that belong to the same IM diagonal are calculated in parallel. The results obtained with real rna sequences show that our GPU version is capable of outperforming a multicore CPU version of the unconstrained version of the Sankoff algorithm. Compared with the CPU-based version running on 32 cores, our approach is able to achieve a speedup of 7.81x on the NVidia Tesla P100. In this case, the execution time was reduced from 6 hours and 18 minutes (32 cores) to 48 minutes and 20 seconds (GPU). © 2019 John Wiley & Sons, Ltd.

关键词： Graphics processing unit

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50 shades of rule composition from chemical reactions to higher levels of abstraction

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Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 2014年 8738卷 115-135页

作者： Andersen, Jakob Lykke Flamm, Christoph Merkle, Daniel Stadler, Peter F. Department of Mathematics and Computer Science University of Southern Denmark Denmark Institute for Theoretical Chemistry University of Vienna Austria Bioinformatics Group Department of Computer Science and Interdisciplinary Center for Bioinformatics Leipzig Germany Max Planck Institute for Mathematics in the Sciences Leipzig Germany Fraunhofer Institute for Cell Therapy and Immunology Leipzig Germany Center for Non-coding RNA in Technology and Health University of Copenhagen Denmark Santa Fe Institute United States

ISBN: (纸本)9783319103976

Graph rewriting has been applied quite successfully to model chemical and biological systems at different levels of abstraction. A particularly powerful feature of rule-based models that are rigorously grounded in category theory, is, that they admit a well-defined notion of rule composition, hence, provide their users with an intrinsic mechanism for compressing trajectories and coarse grained representations of dynamical aspects. The same formal framework, however, also allows the detailed analysis of transitions in which the final and initial states are known, but the detailed stepwise mechanism remains hidden. To demonstrate the general principle we consider here how rule composition is used to determine accurate atom maps for complex enzyme reactions. This problem not only exemplifies the paradigm but is also of considerable practical importance for many down-stream analyses of metabolic networks and it is a necessary prerequisite for predicting atom traces for the analysis of isotope labelling experiments. © Springer International Publishing Switzerland 2014.

关键词： Biological systems

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Identification of valid reference genes for microrna expression studies in a hepatitis B virus replicating liver cell line

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BMC Research Notes 2016年第1期9卷 1-7页

作者： Jacobsen, Kari Stougaard Nielsen, Kirstine Overgaard Winther, Thilde Nordmann Glebe, Dieter Pociot, Flemming Hogh, Birthe Department of Paediatrics Hvidovre Hospital University of Copenhagen Copenhagen Denmark Department of Paediatrics Center for Non-Coding RNA in Technology and Health Herlev Hospital University of Copenhagen Copenhagen Denmark Institute of Medical Virology National Reference Center for Hepatitis B and D Viruses German Center for Infection Research Biomedical Research Center Seltersberg Justus-Liebig University Giessen Giessen Germany

Background: Micrornas are regulatory molecules and suggested as non-invasive biomarkers for molecular diagnostics and prognostics. Altered expression levels of specific micrornas are associated with hepatitis B virus infection and hepatocellular carcinoma. We previously identified differentially expressed micrornas with liver-specific target genes in plasma from children with chronic hepatitis B. To further understand the biological role of these micrornas in the pathogenesis of chronic hepatitis B, we have used the human liver cell line HepG2, with and without HBV replication, after transfection of hepatitis B virus expression vectors. RT-qPCR is the preferred method for microrna studies, and a careful normalisation strategy, verifying the optimal set of reference genes, is decisive for correctly evaluating microrna expression levels. The aim of this study was to provide valid reference genes for the human HCC-derived cell line HepG2. Results: A panel of 739 micrornas was screened to identify the most stably expressed micrornas, followed by a PubMed search identifying micrornas previously used as reference genes. Sixteen candidate reference genes were validated by RT-qPCR. Reference gene stabilities were calculated first by standard deviations of ΔCt values and then by geNorm and NormFinder analyses, taking into account the amplification efficiency of each microrna primer set. The optimal set of reference genes was verified by a target analysis using RT-qPCR on miR-215-5p. Conclusion: We identified miR-24-3p, miR-151a-5p, and miR-425-5p as the most valid combination of reference genes for microrna RT-qPCR studies in our hepatitis B virus replicating HepG2 cell model. © 2016 Jacobsen et al.

关键词： Hepatitis B virus microrna Normalisation Reference genes RT-qPCR

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Computational Discovery of Conserved rna Structures and Functional Characterization of a Structured lncrna in Leishmania braziliensis

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non-coding rna Research 2025年

作者： Caroline R. Espada Christian Anthon Rubens D.M. Magalhães José Carlos Quilles Junior Natalia M.M. Teles Fabiano S. Pais Lissur A. Orsine Letícia de Almeida Tânia P.A. Defina Adam Dowle Jan Gorodkin Pegine B. Walrad Angela K. Cruz Department of Cell and Molecular Biology Ribeirão Preto Medical School University of São Paulo FMRP-USP Ribeirão Preto São Paulo Brasil Department of Biology York Biomedical Research Institute University of York York United Kingdom Center for non-coding RNA in Technology and Health Department of Animal and Veterinary Sciences Faculty for Health and Medical Sciences University of Copenhagen Copenhagen Denmark Data Science Lab Metabolomics and Proteomics Lab Bioscience Technology Facility Department of Biology University of York York United Kingdom

Leishmania parasites alternate between hosts, facing environmental changes that demand rapid gene expression adaptation. Lacking canonical rna polymerase II promoters, transcription in these eukaryotes is polycistronic, with gene regulation occurring post-transcriptionally. Although non-coding rnas (ncrnas) have been identified in Leishmania transcriptomes, their functions remain unclear. Recognizing rna structure's importance, we performed a genome-wide alignment of L. braziliensis and related species, identifying conserved rna structures, 38 of which overlap with known ncrnas. One such ncrna, lncrna45 , was functionally characterized. Using a knockout cell line, we demonstrated that lncrna45 is crucial for parasite fitness. Reintroducing the wild type lncrna45 restored fitness, while a version with a single nucleotide substitution in the structured region did not. This mutation also altered rna-protein interactions. These findings suggest that lncrna45 's regulatory role and protein interactions rely on its secondary structure. This study highlights the significance of structured lncrnas in Leishmania biology and their potential as therapeutic targets. Further research into these ncrnas could uncover new parasite regulation mechanisms and inspire novel treatment strategies.

关键词： non-coding rnas Leishmania braziliensis rna structure Gene expression regulation CRISPR- Cas9

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Comparative ncrna gene and structure prediction using foldalign and foldalignM

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Current Protocols in Bioinformatics 2012年第SUPPL.39期39卷

作者： Havgaard, Jakob Kaur, Simranjeet Gorodkin, Jan Center for Non-Coding RNA in Technology and Health Department of Veterinary Clinical and Animal Sciences University of Copenhagen Copenhagen Denmark

This unit describes how to use Foldalign and FoldalignM to make structural alignments of non-protein-coding-rna (ncrna). These tools can be used to find new ncrnas, to find the structure of novel ncrnas, and to improv... 详细信息

关键词： ncrna ncrna gene finding non-coding rna rna multiple sequence alignment rna structural alignment rna structure prediction

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Dual Fluorescent Protein(yEGFP/DsRed-Express-2) Bioassay System for Rapid Screening for Chemical Mutagens Based on RNR3 Regulation in Saccharomyces Cerevisiae

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Biomedical and Environmental Sciences 2021年第5期34卷 421-424页

作者： LIU Xing CHEN Geng LU Gang Yu YAO Jia ZHU Fang Yu XU Jun LI Xiang Ming Preventive Medicine Department of Yangzhou Medical College Yangzhou UniversityYangzhou 225001JiangsuChina Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001JiangsuChina Institute of Toxicology and Risk Assessment Jiangsu Provincial Center for Disease Control and PreventionNanjing 210009JiangsuChina Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Yangzhou 225001JiangsuChina

Over the past several years,the most widely used in vitro tests for mutagenicity have been those performed on *** include the Ames test,SOS,and SOS/umu chromotest[1,2].The Ames test is the most commonly used system,bu... 详细信息

关键词： SOS/umu automata Ames

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rnai-based therapeutics and tumor targeted delivery in cancer

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ADVANCED DRUG DELIVERY REVIEWS 2022年 182卷 114113-114113页

作者： Kara, Goknur Calin, George A. Ozpolat, Bulent Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Ordu Univ Div Biochem Dept Chem Ordu Turkey Univ Texas MD Anderson Canc Ctr Dept Translat Mol Pathol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA

Over the past decade, non-coding rna-based therapeutics have proven as a great potential for the development of targeted therapies for cancer and other diseases. The discovery of the critical function of micrornas (mirnas) has generated great excitement in developing mirna-based therapies. The dysregulation of mirnas contributes to the pathogenesis of various human diseases and cancers by modulating genes that are involved in critical cellular processes, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, drug resistance, and tumorigenesis. mirna (mirna mimic, anti-mirna/antagomir) and small interfering rna (sirna) can inhibit the expression of any cancer-related genes/mrnas with high specificity through rna interference (rnai), thus representing a remarkable therapeutic tool for targeted therapies and precision medicine. sirna and mirna-based therapies have entered clinical trials and recently three novel sirna-based therapeutics were approved by the Food and Drug Administration (FDA), indicating the beginning of a new era of targeted therapeutics. The successful clinical applications of mirna and sirna therapeutics rely on safe and effective nanodelivery strategies for targeting tumor cells or tumor microenvironment. For this purpose, promising nanodelivery/nanoparticle-based approaches have been developed using a variety of molecules for systemic administration and improved tumor targeted delivery with reduced side effects. In this review, we present an overview of rnai-based therapeutics, the major pharmaceutical challenges, and the perspectives for the development of promising delivery systems for clinical translation. We also highlight the passive and active tumor targeting nanodelivery strategies and primarily focus on the current applications of nanoparticle-based delivery formulations for tumor targeted rnai molecules and their recent advances in clinical trials in human cancers. Published by Elsevier B.V.

关键词： sirna mirna non-coding rnas Cancer Nanoparticles

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Microenvironment and Pathogenesis of Epithelial Ovarian Cancer

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Hormones and Cancer 2010年第6期1卷 277-290页

作者： Saad, Antonio F. Hu, Wei Sood, Anil K. Department of Obstetrics and Gynecology U.T.M.B. Galveston Branch Galveston TX 77555 301 University Blvd United States Department of Gynecologic Oncology U.T.M.D. Anderson Cancer Center Houston TX 77030 1155 Herman Pressler Unit 1362 United States Department of Cancer Biology U.T.M.D. Anderson Cancer Center Houston TX 77030 1515 Holcombe Boulevard Unit 173 United States Center for RNA Interference and Non-Coding RNA Houston TX 77030 1515 Holcombe Boulevard United States Departments of Gynecologic Oncology and Cancer Biology The University of Texas M.D. Anderson Cancer Center Houston TX 77030 1155 Herman Pressler Unit 1362 United States

Multiple genetic alterations play a role in the pathogenesis of ovarian cancer. Although many key proteins and pathways involved in ovarian carcinogenesis and metastasis have been discovered, knowledge of the early steps leading to malignancy remains poorly understood. This poor understanding stems from lack of data from early-stage cancers and absence of a well-established premalignant state universal to all ovarian cancer subtypes. Existing evidence suggests that ovarian cancers develop either through a stepwise mutation process (low-grade pathway), through genetic instability resulting in hastened metastasis (high-grade pathway), or more recently through what has been described as the "'fimbrial-ovarian' serous neoplasia theory." In this latter model, ovarian serous cancers evolve from premalignant lesions in the distal fallopian tube called tubal intraepithelial carcinoma. In this manuscript, we review key genetic and molecular changes that occur in cancer cell progression and suggest a model of ovarian cancer pathogenesis involving both tumor cell mutations and microenvironmental factors. © 2010 Springer Science+Business Media, LLC.

关键词： Carcinogenesis Ovarian cancer

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Targeting non-coding rnas to overcome cancer therapy resistance

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1447-1466页

作者： BaoQing Chen Mihnea P.Dragomir Chen Yang Qiaoqiao Li David Horst George A.Calin Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China Institute of Pathology Charité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlin 10117Germany Berlin Institute of Health Anna-Louisa-Karsch-Straße 210178 BerlinGermany German Cancer Consortium(DKTK) Partner Site BerlinGerman Cancer Research Center(DKFZ)69210 HeidelbergGermany Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA Center for RNA Interference and Non-Coding RNAs The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

It is now well known that non-coding rnas(ncrnas),rather than protein-coding transcripts,are the preponderant rna ***,particularly micrornas(mirnas),long non-coding rnas(lncrnas),and circular rnas(circrnas),are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation,apoptosis,invasion,metastasis,and genomic *** recent discoveries in cancer therapy,resistance to chemotherapy,radiotherapy,targeted therapy.

关键词： chemotherapy metastasis rnas

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Significance of lymphovascular space invasion in epithelial ovarian cancer

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CANCER MEDICINE 2012年第2期1卷 156-164页

作者： Matsuo, Koji Sheridan, Todd B. Yoshino, Kiyoshi Miyake, Takahito Hew, Karina E. Im, Dwight D. Rosenshein, Neil B. Mabuchi, Seiji Enomoto, Takayuki Kimura, Tadashi Sood, Anil K. Roman, Lynda D. Univ So Calif Los Angeles Cty Med Ctr Dept Obstet & Gynecol Div Gynecol Oncol Los Angeles CA 90033 USA Mercy Med Ctr Dept Pathol Baltimore MD USA Osaka Univ Fac Med Dept Obstet & Gynecol Suita Osaka Japan Mercy Med Ctr Gynecol Oncol Ctr Baltimore MD USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Houston TX 77030 USA Univ Texas Houston Ctr RNA Interference & Non Coding RNA Houston TX USA Univ So Calif Los Angeles Cty Med Ctr Norris Comprehens Canc Ctr Womens Canc Program Los Angeles CA 90033 USA

While the prognostic significance of lymphovascular space invasion (LVSI) is well established in endometrial and cervical cancer, its role in ovarian cancer is not fully understood. First, a training cohort was conducted to explore whether the presence and quantity of LVSI within the ovarian tumor correlated with nodal metastasis and survival (n = 127). Next, the results of the training cohort were applied to a different study population (validation cohort, n = 93). In both cohorts, histopathology slides of epithelial ovarian cancer cases that underwent primary cytoreductive surgery including pelvic and/or aortic lymphadenectomy were examined. In a post hoc analysis, the significance of LVSI was evaluated in apparent stage I cases (n = 53). In the training cohort, the majority of patients had advanced-stage disease (82.7%). LVSI was observed in 79.5% of cases, and nodal metastasis was the strongest variable associated with the presence of LVSI (odds ratio [OR]: 7.99, 95% confidence interval [CI]: 1.98-32.1, P = 0.003) in multivariate analysis. The presence of LVSI correlated with a worsened progression-free survival on multivariate analysis (hazard ratio [HR]: 2.06, 95% CI: 1.01-4.24, P = 0.048). The significance of the presence of LVSI was reproduced in the validation cohort (majority, early stage 61.3%). In apparent stage I cases, the presence of LVSI was associated with a high negative predictive value for nodal metastasis (100%, likelihood ratio, P = 0.034) and with worsened progression-free survival (HR: 5.16, 95% CI: 1.00-26.6, P = 0.028). The presence of LVSI is an independent predictive indicator of nodal metastasis and is associated with worse clinical outcome of patients with epithelial ovarian cancer.

关键词： Lymph node metastasis lymphovascular space invasion ovarian cancer survival

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