41 research outputs found

    Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo

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    <p>Abstract</p> <p>Background</p> <p>Telomerase activation, a critical step in cell immortalization and oncogenesis, is partly regulated by alternative splicing. In this study, we aimed to use the Marek's disease virus (MDV) T-cell lymphoma model to evaluate TERT regulation by splicing during lymphomagenesis <it>in vivo</it>, from the start point to tumor establishment.</p> <p>Results</p> <p>We first screened cDNA libraries from the chicken MDV lymphoma-derived MSB-1 T- cell line, which we compared with B (DT40) and hepatocyte (LMH) cell lines. The chTERT splicing pattern was cell line-specific, despite similar high levels of telomerase activity. We identified 27 alternative transcripts of chicken TERT (chTERT). Five were in-frame alternative transcripts without <it>in vitro </it>telomerase activity in the presence of viral or chicken telomerase RNA (vTR or chTR), unlike the full-length transcript. Nineteen of the 22 transcripts with a premature termination codon (PTC) harbored a PTC more than 50 nucleotides upstream from the 3' splice junction, and were therefore predicted targets for nonsense-mediated decay (NMD). The major PTC-containing alternatively spliced form identified in MSB1 (ie10) was targeted to the NMD pathway, as demonstrated by UPF1 silencing. We then studied three splicing events separately, and the balance between in-frame alternative splice variants (d5f and d10f) plus the NMD target i10ec and constitutively spliced chTERT transcripts during lymphomagenesis induced by MDV indicated that basal telomerase activity in normal T cells was associated with a high proportion of in-frame non functional isoforms and a low proportion of constitutively spliced chTERT. Telomerase upregulation depended on an increase in active constitutively spliced chTERT levels and coincided with a switch in alternative splicing from an in-frame variant to NMD-targeted variants.</p> <p>Conclusions</p> <p>TERT regulation by splicing plays a key role in telomerase upregulation during lymphomagenesis, through the sophisticated control of constitutive and alternative splicing. Using the MDV T-cell lymphoma model, we identified a chTERT splice variant as a new NMD target.</p

    This volume was born from the experience of the authors as researchers and educators, which suggests that many students of data mining are handicapped in their research by the lack of a formal, systematic education in its mathematics.The data mining literature contains many excellent titles that address the needs of users with a variety of interests ranging from decision making to pattern investigation in biological data. However, these books do not deal with the mathematical tools that are currently needed by data mining researchers and doctoral students. We felt it timely to produce a book that integrates the mathematics of data mining with its applications. We emphasize that this book is about mathematical tools for data mining and not about data mining itself; despite this, a substantial amount of applications of mathematical concepts in data mining are presented. The book is intended as a reference for the working data miner.In our opinion, three areas of mathematics are vital for data mining: set theory, including partially ordered sets and combinatorics; linear algebra, with its many applications in principal component analysis and neural networks; and probability theory, which plays a foundational role in statistics, machine learning and data mining.This volume is dedicated to the study of set-theoretical foundations of data mining. Two further volumes are contemplated that will cover linear algebra and probability theory.

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    Outils mathématiques pour la fouille des données - Théorie des ensembles, Ordre partiel, Combinatoires. Deuxième édition.

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    Second edition 2014. The first edition - 2008International audienc

    Mathematical tools for data mining: set theory, partial orders, combinatorics

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    The maturing of the field of data mining has brought about an increased level of mathematical sophistication. Such disciplines like topology, combinatorics, partially ordered sets and their associated algebraic structures (lattices and Boolean algebras), and metric spaces are increasingly applied in data mining research. This book presents these mathematical foundations of data mining integrated with applications to provide the reader with a comprehensive reference. Mathematics is presented in a thorough and rigorous manner offering a detailed explanation of each topic, with applications to data mining such as frequent item sets, clustering, decision trees also being discussed. More than 400 exercises are included and they form an integral part of the material. Some of the exercises are in reality supplemental material and their solutions are included. The reader is assumed to have a knowledge of elementary analysis. Features and topics: a Study of functions and relations a Applications are provided throughout a Presents graphs and hypergraphs a Covers partially ordered sets, lattices and Boolean algebras a Finite partially ordered sets a Focuses on metric spaces a Includes combinatorics a Discusses the theory of the Vapnik-Chervonenkis dimension of collections of sets This wide-ranging, thoroughly detailed volume is self-contained and intended for researchers and graduate students, and will prove an invaluable reference tool

    Clustering by Random Projections

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