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      UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein–DNA interactions

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          Abstract

          The Universal PBM Resource for Oligonucleotide Binding Evaluation (UniPROBE) serves as a convenient source of information on published data generated using universal protein-binding microarray (PBM) technology, which provides in vitro data about the relative DNA-binding preferences of transcription factors for all possible sequence variants of a length k (‘ k-mers’). The database displays important information about the proteins and displays their DNA-binding specificity data in terms of k-mers, position weight matrices and graphical sequence logos. This update to the database documents the growth of UniPROBE since the last update 4 years ago, and introduces a variety of new features and tools, including a new streamlined pipeline that facilitates data deposition by universal PBM data generators in the research community, a tool that generates putative nonbinding (i.e. negative control) DNA sequences for one or more proteins and novel motifs obtained by analyzing the PBM data using the BEEML-PBM algorithm for motif inference. The UniPROBE database is available at http://uniprobe.org.

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          Most cited references27

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          JASPAR: an open-access database for eukaryotic transcription factor binding profiles.

          The analysis of regulatory regions in genome sequences is strongly based on the detection of potential transcription factor binding sites. The preferred models for representation of transcription factor binding specificity have been termed position-specific scoring matrices. JASPAR is an open-access database of annotated, high-quality, matrix-based transcription factor binding site profiles for multicellular eukaryotes. The profiles were derived exclusively from sets of nucleotide sequences experimentally demonstrated to bind transcription factors. The database is complemented by a web interface for browsing, searching and subset selection, an online sequence analysis utility and a suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. JASPAR is available at http://jaspar. cgb.ki.se.
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            DNA binding sites: representation and discovery.

            G Stormo (2000)
            The purpose of this article is to provide a brief history of the development and application of computer algorithms for the analysis and prediction of DNA binding sites. This problem can be conveniently divided into two subproblems. The first is, given a collection of known binding sites, develop a representation of those sites that can be used to search new sequences and reliably predict where additional binding sites occur. The second is, given a set of sequences known to contain binding sites for a common factor, but not knowing where the sites are, discover the location of the sites in each sequence and a representation for the specificity of the protein.
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              Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences.

              Most homeodomains are unique within a genome, yet many are highly conserved across vast evolutionary distances, implying strong selection on their precise DNA-binding specificities. We determined the binding preferences of the majority (168) of mouse homeodomains to all possible 8-base sequences, revealing rich and complex patterns of sequence specificity and showing that there are at least 65 distinct homeodomain DNA-binding activities. We developed a computational system that successfully predicts binding sites for homeodomain proteins as distant from mouse as Drosophila and C. elegans, and we infer full 8-mer binding profiles for the majority of known animal homeodomains. Our results provide an unprecedented level of resolution in the analysis of this simple domain structure and suggest that variation in sequence recognition may be a factor in its functional diversity and evolutionary success.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                28 January 2015
                05 November 2014
                05 November 2014
                : 43
                : Database issue , Database issue
                : D117-D122
                Affiliations
                [1 ]Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
                [2 ]Bioinformatics Graduate Program, Northeastern University, Boston, MA 02115, USA
                [3 ]Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA
                [4 ]Bioinformatics and Integrative Genomics Graduate Program, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA
                [5 ]Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +1 617 525 4725; Fax: +1 617 525 4705; Email: mlbulyk@ 123456receptor.med.harvard.edu
                Author information
                http://orcid.org/0000-0003-2877-8079
                Article
                10.1093/nar/gku1045
                4383892
                25378322
                c627e8e8-08aa-4f1f-abc1-dfc63cf43798
                © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 12 October 2014
                : 15 September 2014
                Page count
                Pages: 6
                Categories
                Database Issue
                Custom metadata
                28 January 2015

                Genetics
                Genetics

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