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                    "firstName": "Bin",
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            "abstractNote": "Motivation: Compared with complementary DNA (cDNA) or messenger RNA (mRNA) microarray data, microRNA (miRNA) microarray data are harder to normalize due to the facts that the total number of miRNAs is small, and that the majority of miRNAs usually have low expression levels. In bead-based microarrays, the hybridization is completed in several pools. As a result, the number of miRNAs tested in each pool is even smaller, which poses extra difficulty to intrasample normalization and ultimately affects the quality of the final profiles assembled from various pools. In this article, we consider a measurement error model-based method for bead-based microarray intrasample normalization.Results: In this study, results from quantitative real-time PCR (qRT-PCR) assays are used as ‘gold standards’ for validation. The performance of the proposed measurement error model-based method is evaluated via a simulation study and real bead-based miRNA expression data. Simulation results show that the new method performs well to assemble complete profiles from subprofiles from various pools. Compared with two intrasample normalization methods recommended by the manufacturer, the proposed approach produces more robust final complete profiles and results in better agreement with the qRT-PCR results in identifying differentially expressed miRNAs, and hence improves the reproducibility between the two microarray platforms. Meaningful results are obtained by the proposed intrasample normalization method, together with quantile normalization as a subsequent complemental intersample normalization method.Availability: Datasets and R package are available at http://gauss.usouthal.edu/publ/beadsme/.Contact: bwang@jaguar1.usouthal.edu",
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            "date": "June 01 , 2011",
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            "abstractNote": "MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.",
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                    "firstName": "Michael J",
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                    "firstName": "Jakub O",
                    "lastName": "Westholm"
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                    "firstName": "Eric C",
                    "lastName": "Lai"
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            "date": "2011",
            "volume": "12",
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            "pages": "221",
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            "title": "A detailed investigation of accessibilities around target sites of siRNAs and miRNAs",
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                {
                    "creatorType": "author",
                    "firstName": "Hisanori",
                    "lastName": "Kiryu"
                },
                {
                    "creatorType": "author",
                    "firstName": "Goro",
                    "lastName": "Terai"
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                {
                    "creatorType": "author",
                    "firstName": "Osamu",
                    "lastName": "Imamura"
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                {
                    "creatorType": "author",
                    "firstName": "Hiroyuki",
                    "lastName": "Yoneyama"
                },
                {
                    "creatorType": "author",
                    "firstName": "Kenji",
                    "lastName": "Suzuki"
                },
                {
                    "creatorType": "author",
                    "firstName": "Kiyoshi",
                    "lastName": "Asai"
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            ],
            "abstractNote": "MOTIVATION: The importance of RNA sequence analysis has been increasing since the discovery of various types of non-coding RNAs transcribed in animal cells. Conventional RNA sequence analyses have mainly focused on structured regions, which are stabilized by the stacking energies acting on adjacent base pairs. On the other hand, recent findings regarding the mechanisms of small interfering RNAs (siRNAs) and transcription regulation by microRNAs (miRNAs) indicate the importance analyzing accessible regions where no base pairs exist. So far, relatively few studies have investigated the nature of such regions. RESULTS: We have conducted a detailed investigation of accessibilities around the target sites of siRNAs and miRNAs. We have exhaustively calculated the correlations between the accessibilities around the target sites and the repression levels of the corresponding mRNAs. We have computed the accessibilities with an originally developed software package, called \"Raccess\", which computes the accessibility of all the segments of a fixed length for a given RNA sequence when the maximal distance between base pairs is limited to a fixed size W. We show that the computed accessibilities are relatively insensitive to the choice of the maximal span W. We have found that the efficacy of siRNAs depends strongly on the accessibility of the very 3'-end of their binding sites, which might reflect a target site recognition mechanism in the RISC complex. We also show that the efficacy of miRNAs has a similar dependence on the accessibilities, but some miRNAs also show positive correlations between the efficacy and the accessibilities in broad regions downstream of their putative binding sites, which might imply that the downstream regions of the target sites are bound by other proteins that allow the miRNAs to implement their functions. We have also investigated the off-target effects of an siRNA as a potential RNAi therapeutic. We show that the off-target effects of the siRNA have similar correlations to the miRNA repression, indicating that they are caused by the same mechanism. AVAILABILITY: The C++ source code of the Raccess software is available at http://www.ncrna.org/software/Raccess/ The microarray data on the measurements of the siRNA off-target effects are also available at the same site. CONTACT: kiryu-h@k.u-tokyo.ac.jp.",
            "publicationTitle": "Bioinformatics (Oxford, England)",
            "publisher": "",
            "place": "",
            "date": "Apr 29, 2011",
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            "seriesTitle": "",
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            "journalAbbreviation": "Bioinformatics",
            "DOI": "10.1093/bioinformatics/btr276",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/21531769",
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            "PMCID": "",
            "ISSN": "1367-4811",
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            "creatorSummary": "Zhang and Zhang",
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            "title": "Histone modification profiles are predictive for tissue/cell-type specific expression of both protein-coding and microRNA genes",
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                    "creatorType": "author",
                    "firstName": "Zhihua",
                    "lastName": "Zhang"
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                    "firstName": "Michael Q",
                    "lastName": "Zhang"
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            "abstractNote": "ABSTRACT: BACKGROUND: Gene expression is regulated at both the DNA sequence level and through modification of chromatin. However, the effect of chromatin on tissue/cell-type specific gene regulation (TCSR) is largely unknown. In this paper, we present a method to elucidate the relationship between histone modification/variation (HMV) and TCSR. RESULTS: A classifier for differentiating CD4+ T cell-specific genes from housekeeping genes using HMV data was built. We found HMV in both promoter and gene body regions to be predictive of genes which are targets of TCSR. For example, the histone modification types H3K4me3 and H3K27ac were identified as the most predictive for CpG-related promoters, whereas H3K4me3 and H3K79me3 were the most predictive for nonCpG-related promoters. However, genes targeted by TCSR can be predicted using other type of HMVs as well. Such redundancy implies that multiple type of underlying regulatory elements, such as enhancers or intragenic alternative promoters, which can regulate gene expression in a tissue/cell-type specific fashion, may be marked by the HMVs. Finally, we show that the predictive power of HMV for TCSR is not limited to protein-coding genes in CD4+ T cells, as we successfully predicted TCSR targeted genes in muscle cells, as well as microRNA genes with expression specific to CD4+ T cells, by the same classifier which were trained on HMV data of protein-coding genes in CD4+ T cells. CONCLUSION: We have begun to understand the HMV patterns that guide gene expression in both tissue/cell-type specific and ubiquitous manner.",
            "publicationTitle": "BMC Bioinformatics",
            "publisher": "",
            "place": "",
            "date": "May 14, 2011",
            "volume": "12",
            "issue": "1",
            "section": "",
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            "partTitle": "",
            "pages": "155",
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            "journalAbbreviation": "BMC Bioinformatics",
            "DOI": "10.1186/1471-2105-12-155",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/21569556",
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            "ISSN": "1471-2105",
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            "extra": "PMID: 21569556",
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                {
                    "tag": "mirna-regulation"
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            "dateAdded": "2011-05-26T17:35:33Z",
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    {
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            "creatorSummary": "Ellwanger et al.",
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            "title": "The sufficient minimal set of miRNA seed types",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Daniel C.",
                    "lastName": "Ellwanger"
                },
                {
                    "creatorType": "author",
                    "firstName": "Florian A.",
                    "lastName": "Büttner"
                },
                {
                    "creatorType": "author",
                    "firstName": "Hans-Werner",
                    "lastName": "Mewes"
                },
                {
                    "creatorType": "author",
                    "firstName": "Volker",
                    "lastName": "Stümpflen"
                }
            ],
            "abstractNote": "Motivation: Pairing between the target sequence and the 6–8 nt long seed sequence of the miRNA presents the most important feature for miRNA target site prediction. Novel high-throughput technologies such as Argonaute HITS-CLIP afford meanwhile a detailed study of miRNA:mRNA duplices. These interaction maps enable a first discrimination between functional and non-functional target sites in a bulky fashion. Prediction algorithms apply different seed paradigms to identify miRNA target sites. Therefore, a quantitative assessment of miRNA target site prediction is of major interest.Results: We identified a set of canonical seed types based on a transcriptome wide analysis of experimentally verified functional target sites. We confirmed the specificity of long seeds but we found that the majority of functional target sites are formed by less specific seeds of only 6 nt indicating a crucial role of this type. A substantial fraction of genuine target sites arenon-conserved. Moreover, the majority of functional sites remain uncovered by common prediction methods.Contact: florian.buettner@helmholtz-muenchen.de v.stuempflen@helmholtz-muenchen.deSupplementary Information: Supplementary data are available at Bioinformatics online.",
            "publicationTitle": "Bioinformatics",
            "publisher": "",
            "place": "",
            "date": "May 15 , 2011",
            "volume": "27",
            "issue": "10",
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            "partNumber": "",
            "partTitle": "",
            "pages": "1346 -1350",
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            "DOI": "10.1093/bioinformatics/btr149",
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            "url": "http://bioinformatics.oxfordjournals.org/content/27/10/1346.abstract",
            "accessDate": "2011-05-24T21:10:19Z",
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            "dateAdded": "2011-05-26T17:34:38Z",
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            "creatorSummary": "Su et al.",
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            "title": "Characterizing the role of miRNAs within gene regulatory networks using integrative genomics techniques",
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                    "firstName": "Wan-Lin",
                    "lastName": "Su"
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                {
                    "creatorType": "author",
                    "firstName": "Robert R",
                    "lastName": "Kleinhanz"
                },
                {
                    "creatorType": "author",
                    "firstName": "Eric E",
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            ],
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            "publicationTitle": "Mol Syst Biol",
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            "date": "May 24, 2011",
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            "journalAbbreviation": "Mol Syst Biol",
            "DOI": "10.1038/msb.2011.23",
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            "dateAdded": "2011-05-26T17:34:26Z",
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