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  1. Article ; Online: miRNA target identification and prediction as a function of time in gene expression data.

    Grigaitis, Pranas / Starkuviene, Vytaute / Rost, Ursula / Serva, Andrius / Pucholt, Pascal / Kummer, Ursula

    RNA biology

    2020  Volume 17, Issue 7, Page(s) 990–1000

    Abstract: The understanding of miRNA target interactions is still limited due to conflicting data and the fact that high-quality validation of targets is a time-consuming process. Faster methods like high-throughput screens and bioinformatics predictions are ... ...

    Abstract The understanding of miRNA target interactions is still limited due to conflicting data and the fact that high-quality validation of targets is a time-consuming process. Faster methods like high-throughput screens and bioinformatics predictions are employed but suffer from several problems. One of these, namely the potential occurrence of downstream (i.e. secondary) effects in high-throughput screens has been only little discussed so far. However, such effects limit usage for both the identification of interactions and for the training of bioinformatics tools. In order to analyse this problem more closely, we performed time-dependent microarray screening experiments overexpressing human miR-517a-3p, and, together with published time-dependent datasets of human miR-17-5p, miR-135b and miR-124 overexpression, we analysed the dynamics of deregulated genes. We show that the number of deregulated targets increases over time, whereas seed sequence content and performance of several miRNA target prediction algorithms actually decrease over time. Bioinformatics recognition success of validated miR-17 targets was comparable to that of data gained only 12 h post-transfection. We therefore argue that the timing of microarray experiments is of critical importance for detecting direct targets with high confidence and for the usability of these data for the training of bioinformatics prediction tools.
    MeSH term(s) Algorithms ; Computational Biology/methods ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; MicroRNAs/genetics ; RNA, Messenger/genetics ; Reproducibility of Results ; Transcriptome
    Chemical Substances MicroRNAs ; RNA, Messenger
    Language English
    Publishing date 2020-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2159587-2
    ISSN 1555-8584 ; 1555-8584
    ISSN (online) 1555-8584
    ISSN 1555-8584
    DOI 10.1080/15476286.2020.1748921
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: miRNA target identification and prediction as a function of time in gene expression data

    Grigaitis, Pranas / Starkuviene, Vytaute / Rost, Ursula / Serva, Andrius / Pucholt, Pascal / Kummer, Ursula

    RNA biology. 2020 July 02, v. 17, no. 7

    2020  

    Abstract: The understanding of miRNA target interactions is still limited due to conflicting data and the fact that high-quality validation of targets is a time-consuming process. Faster methods like high-throughput screens and bioinformatics predictions are ... ...

    Abstract The understanding of miRNA target interactions is still limited due to conflicting data and the fact that high-quality validation of targets is a time-consuming process. Faster methods like high-throughput screens and bioinformatics predictions are employed but suffer from several problems. One of these, namely the potential occurrence of downstream (i.e. secondary) effects in high-throughput screens has been only little discussed so far. However, such effects limit usage for both the identification of interactions and for the training of bioinformatics tools. In order to analyse this problem more closely, we performed time-dependent microarray screening experiments overexpressing human miR-517a-3p, and, together with published time-dependent datasets of human miR-17-5p, miR-135b and miR-124 overexpression, we analysed the dynamics of deregulated genes. We show that the number of deregulated targets increases over time, whereas seed sequence content and performance of several miRNA target prediction algorithms actually decrease over time. Bioinformatics recognition success of validated miR-17 targets was comparable to that of data gained only 12 h post-transfection. We therefore argue that the timing of microarray experiments is of critical importance for detecting direct targets with high confidence and for the usability of these data for the training of bioinformatics prediction tools.
    Keywords algorithms ; bioinformatics ; gene overexpression ; genes ; humans ; microRNA ; microarray technology ; prediction ; screening
    Language English
    Dates of publication 2020-0702
    Size p. 990-1000.
    Publishing place Taylor & Francis
    Document type Article
    ISSN 1555-8584
    DOI 10.1080/15476286.2020.1748921
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: A Potential of microRNAs for High-Content Screening.

    Serva, Andrius / Claas, Christoph / Starkuviene, Vytaute

    Journal of nucleic acids

    2011  Volume 2011, Page(s) 870903

    Abstract: In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance ... ...

    Abstract In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.
    Language English
    Publishing date 2011-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2549000-X
    ISSN 2090-021X ; 2090-021X
    ISSN (online) 2090-021X
    ISSN 2090-021X
    DOI 10.4061/2011/870903
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Online ; Thesis: Functional Analysis of MicroRNAs as Regulators of Membrane Trafficking

    Serva, Andrius [Verfasser] / Eils, Roland [Akademischer Betreuer]

    2012  

    Author's details Andrius Serva ; Betreuer: Roland Eils
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universitätsbibliothek Heidelberg
    Publishing place Heidelberg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  5. Article ; Online: A Potential of microRNAs for High-Content Screening

    Vytaute Starkuviene / Andrius Serva / Christoph Claas

    Journal of Nucleic Acids, Vol

    2011  Volume 2011

    Keywords Genetics ; QH426-470 ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Genetics ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Biochemistry ; QD415-436 ; Organic chemistry ; QD241-441 ; Chemistry ; QD1-999 ; DOAJ:Biochemistry ; DOAJ:Life Sciences
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Capture and Amplification by Tailing and Switching (CATS). An ultrasensitive ligation-independent method for generation of DNA libraries for deep sequencing from picogram amounts of DNA and RNA.

    Turchinovich, Andrey / Surowy, Harald / Serva, Andrius / Zapatka, Marc / Lichter, Peter / Burwinkel, Barbara

    RNA biology

    2014  Volume 11, Issue 7, Page(s) 817–828

    Abstract: Massive parallel sequencing (MPS) technologies have paved the way into new areas of research including individualized medicine. However, sequencing of trace amounts of DNA or RNA still remains a major challenge, especially for degraded nucleic acids like ...

    Abstract Massive parallel sequencing (MPS) technologies have paved the way into new areas of research including individualized medicine. However, sequencing of trace amounts of DNA or RNA still remains a major challenge, especially for degraded nucleic acids like circulating DNA. This together with high cost and time requirements impedes many important applications of MPS in medicine and fundamental science. We have established a fast, cheap and highly efficient protocol called 'Capture and Amplification by Tailing and Switching' (CATS) to directly generate ready-to-sequence libraries for MPS from nanogram and picogram quantities of both DNA and RNA. Furthermore, those DNA libraries are strand-specific, can be prepared within 2-3 h and do not require preliminary sample amplification steps. To exemplify the capacity of the technique, we have generated and sequenced DNA libraries from hundred-picogram amounts of circulating nucleic acids isolated from human blood plasma, one nanogram of mRNA-enriched total RNA from cultured cells and few nanograms of bisulfite-converted DNA. The approach for DNA library preparation from minimal and fragmented input described here will find broad application in diverse research areas such as translational medicine including therapy monitoring, prediction, prognosis and early detection of various human disorders and will permit high-throughput DNA sequencing from previously inaccessible material such as minute forensic and archeological samples.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Cell Line, Tumor ; DNA/blood ; DNA/genetics ; Gene Library ; High-Throughput Nucleotide Sequencing/economics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; RNA/blood ; RNA/genetics ; Sequence Analysis, DNA/economics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/economics ; Sequence Analysis, RNA/methods ; Time Factors
    Chemical Substances RNA (63231-63-0) ; DNA (9007-49-2)
    Language English
    Publishing date 2014-06-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1555-8584
    ISSN (online) 1555-8584
    DOI 10.4161/rna.29304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs

    Raquel M. Melero-Fernandez de Mera / Li-Li Li / Arkadiusz Popinigis / Katryna Cisek / Minna Tuittila / Leena Yadav / Andrius Serva / Michael J. Courtney

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 18

    Abstract: Light-sensitive regulators of protein kinases could offer valuable insights into intracellular signalling. Here the authors design an optogenetic inhibitor of c-Jun N-terminal kinase (JNK) and show evidence for resonance in JNK signalling circuits in ... ...

    Abstract Light-sensitive regulators of protein kinases could offer valuable insights into intracellular signalling. Here the authors design an optogenetic inhibitor of c-Jun N-terminal kinase (JNK) and show evidence for resonance in JNK signalling circuits in neurons, and use the same design principle to develop an inhibitor for p38MAPK.
    Keywords Science ; Q
    Language English
    Publishing date 2017-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A simple optogenetic MAPK inhibitor design reveals resonance between transcription-regulating circuitry and temporally-encoded inputs.

    Melero-Fernandez de Mera, Raquel M / Li, Li-Li / Popinigis, Arkadiusz / Cisek, Katryna / Tuittila, Minna / Yadav, Leena / Serva, Andrius / Courtney, Michael J

    Nature communications

    2017  Volume 8, Page(s) 15017

    Abstract: Engineering light-sensitive protein regulators has been a tremendous multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of cellular regulation, have not previously been described. Here we present OptoJNKi, a light-regulated JNK ... ...

    Abstract Engineering light-sensitive protein regulators has been a tremendous multidisciplinary challenge. Optogenetic regulators of MAPKs, central nodes of cellular regulation, have not previously been described. Here we present OptoJNKi, a light-regulated JNK inhibitor based on the AsLOV2 light-sensor domain using the ubiquitous FMN chromophore. OptoJNKi gene-transfer allows optogenetic applications, whereas protein delivery allows optopharmacology. Development of OptoJNKi suggests a design principle for other optically regulated inhibitors. From this, we generate Optop38i, which inhibits p38MAPK in intact illuminated cells. Neurons are known for interpreting temporally-encoded inputs via interplay between ion channels, membrane potential and intracellular calcium. However, the consequences of temporal variation of JNK-regulating trophic inputs, potentially resulting from synaptic activity and reversible cellular protrusions, on downstream targets are unknown. Using OptoJNKi, we reveal maximal regulation of c-Jun transactivation can occur at unexpectedly slow periodicities of inhibition depending on the inhibitor's subcellular location. This provides evidence for resonance in metazoan JNK-signalling circuits.
    MeSH term(s) Animals ; Avena/genetics ; Avena/metabolism ; COS Cells ; Cells, Cultured ; Cercopithecus aethiops ; Drug Design ; Female ; HEK293 Cells ; Humans ; Light ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/genetics ; MAP Kinase Signaling System/radiation effects ; Male ; Neurons/drug effects ; Neurons/metabolism ; Neurons/radiation effects ; Optogenetics/methods ; Phototropins/chemistry ; Phototropins/genetics ; Phototropins/metabolism ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Rats ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
    Chemical Substances Phototropins ; Protein Kinase Inhibitors ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2017-05-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/ncomms15017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Short, terminally modified 2'-OMe RNAs as inhibitors of microRNA.

    Blechinger, Jenny / Pieper, Hanna / Marzenell, Paul / Kovbasyuk, Larisa / Serva, Andrius / Starkuviene, Vytaute / Erfle, Holger / Mokhir, Andriy

    Chemical communications (Cambridge, England)

    2013  Volume 49, Issue 67, Page(s) 7397–7399

    Abstract: We applied 14-mer 2'-OMe RNAs as inhibitors of selected micro RNAs. To improve their properties, we introduced a trimethoxystilbene residue at the 5'-terminus and three 2'-fluoro-2'-deoxynucleotides at the 3'-terminus to obtain potent inhibitors, whose ... ...

    Abstract We applied 14-mer 2'-OMe RNAs as inhibitors of selected micro RNAs. To improve their properties, we introduced a trimethoxystilbene residue at the 5'-terminus and three 2'-fluoro-2'-deoxynucleotides at the 3'-terminus to obtain potent inhibitors, whose mismatch discrimination is substantially better than that of typically applied >18-mers.
    MeSH term(s) Base Sequence ; Down-Regulation/drug effects ; HeLa Cells ; Humans ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/chemistry ; Oligonucleotides/chemistry ; Oligonucleotides/pharmacology ; Stilbenes/chemistry ; Stilbenes/pharmacology
    Chemical Substances MicroRNAs ; Oligonucleotides ; Stilbenes
    Language English
    Publishing date 2013-08-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1472881-3
    ISSN 1364-548X ; 1359-7345 ; 0009-241X
    ISSN (online) 1364-548X
    ISSN 1359-7345 ; 0009-241X
    DOI 10.1039/c3cc43174f
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Multi-element analysis of single nanoparticles by ICP-MS using quadrupole and time-of-flight technologies

    Naasz, Steffi / Weigel, Stefan / Borovinskaya, Olga / Serva, Andrius / Cascio, Claudia / Undas, Anna K. / Simeone, Felice C. / Marvin, Hans J. P. / Peters, Ruud J. B.

    2018  

    Abstract: Determining composition, shape, and size of nanoparticles dispersed in a complex matrix is necessary in the assessment of toxicity, for regulatory actions, and environmental monitoring. Many types of nanoparticles that are currently used in consumer ... ...

    Abstract Determining composition, shape, and size of nanoparticles dispersed in a complex matrix is necessary in the assessment of toxicity, for regulatory actions, and environmental monitoring. Many types of nanoparticles that are currently used in consumer products contain more than one metal which are often not uniformly distributed (e.g., core-shell nanoparticles). This compositional and structural complexity makes their characterization difficult. In this study, we investigate the capability of single particle inductively coupled plasma mass spectrometry (spICP-MS) using time-of-flight (TOF) and quadrupole (Q) mass analyzers to determine the composition, size distribution, and concentration of a series of nanoparticles that are used in a variety of industrial applications: BiVO4, (Bi0.5Na0.5)TiO3 and steel (which contains Fe, Cr, Ni, Mo) nanoparticles. In addition, we tested both types of mass analyzers with Au-core/Ag-shell nanoparticles, which are well-characterized and have already been used for assessment of multi-element capabilities of spICP-MS. The results confirm that both types of mass analyzers produce accurate estimations of the size of Au-core/Ag-shell particles. For other multi-element nanoparticles, spICP-MS provided the size of aggregates and/or agglomerates in the prepared suspensions. In general, particle size detection limits (dLOD) of spICP-TOFMS instruments with values of 29 nm for Ti, 14 nm for Mo, and 7 nm for Au, are smaller than those obtained for the quadrupole instruments. This study finds that only spICP-TOFMS can accurately assess the elemental composition of nano-steel particles. By contrast, spICP-QMS is limited to the detection of 2 elements in an individual particle and the elemental composition of nano-steel particles is less accurate. In general, spICP-TOFMS was able to quantify multiple elements with high precision and that currently makes it the first choice for multi-element detection of unknown nanoparticles.
    Keywords Text ; ddc:540
    Subject code 620
    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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