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  • 1
    Publication Date: 2012-08-25
    Description: : The functional annotation of variants obtained through sequencing projects is generally assumed to be a simple intersection of genomic coordinates with genomic features. However, complexities arise for several reasons, including the differential effects of a variant on alternatively spliced transcripts, as well as the difficulty in assessing the impact of small insertions/deletions and large structural variants. Taking these factors into consideration, we developed the Variant Annotation Tool (VAT) to functionally annotate variants from multiple personal genomes at the transcript level as well as obtain summary statistics across genes and individuals. VAT also allows visualization of the effects of different variants, integrates allele frequencies and genotype data from the underlying individuals and facilitates comparative analysis between different groups of individuals. VAT can either be run through a command-line interface or as a web application. Finally, in order to enable on-demand access and to minimize unnecessary transfers of large data files, VAT can be run as a virtual machine in a cloud-computing environment. Availability and Implementation: VAT is implemented in C and PHP. The VAT web service, Amazon Machine Image, source code and detailed documentation are available at vat.gersteinlab.org. Contact: lukas.habegger@yale.edu or mark.gerstein@yale.edu Supplementary Information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 2
    Publication Date: 2018-09-28
    Description: To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes revealed sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, which is defined as random transitions between fully methylated and unmethylated states of DNA. The methylation imbalances at thousands of loci are explainable by different relative frequencies of the methylated and unmethylated states for the two alleles. Further analyses provided a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci, and disease-associated genetic variation.
    Keywords: Genetics, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-03-09
    Description: Precise identification of RNA-coding regions and transcriptomes of eukaryotes is a significant problem in biology. Currently, eukaryote transcriptomes are analyzed using deep short-read sequencing experiments of complementary DNAs. The resulting short-reads are then aligned against a genome and annotated junctions to infer biological meaning. Here we use long-read complementary DNA datasets for the analysis of a eukaryotic transcriptome and generate two large datasets in the human K562 and HeLa S3 cell lines. Both data sets comprised at least 4 million reads and had median read lengths greater than 500 bp. We show that annotation-independent alignments of these reads provide partial gene structures that are very much in-line with annotated gene structures, 15% of which have not been obtained in a previous de novo analysis of short reads. For long-noncoding RNAs ( i.e. , lncRNA) genes, however, we find an increased fraction of novel gene structures among our alignments. Other important aspects of transcriptome analysis, such as the description of cell type-specific splicing, can be performed in an accurate, reliable and completely annotation-free manner, making it ideal for the analysis of transcriptomes of newly sequenced genomes. Furthermore, we demonstrate that long read sequence can be assembled into full-length transcripts with considerable success. Our method is applicable to all long read sequencing technologies.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 4
    Publication Date: 2013-10-16
    Description: Article Mice deficient in the E3 ubiquitin ligase Smurf2 spontaneously develop B-cell lymphomas. Here Ramkumar et al. show that Smurf2 regulates B-cell proliferation by ubiquitinating the transcription factor YY1, and that Smurf2 expression correlates negatively with survival of patients with diffuse large B-cell lymphoma. Nature Communications doi: 10.1038/ncomms3598 Authors: Charusheila Ramkumar, Hang Cui, Yahui Kong, Stephen N. Jones, Rachel M. Gerstein, Hong Zhang
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 5
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2000-06-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerstein, M -- New York, N.Y. -- Science. 2000 Jun 2;288(5471):1590.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10858136" target="_blank"〉PubMed〈/a〉
    Keywords: Databases, Factual ; *Genome, Human ; Humans ; Peer Review, Research ; Periodicals as Topic ; *Publishing
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2001-07-28
    Description: To facilitate studies of the yeast proteome, we cloned 5800 open reading frames and overexpressed and purified their corresponding proteins. The proteins were printed onto slides at high spatial density to form a yeast proteome microarray and screened for their ability to interact with proteins and phospholipids. We identified many new calmodulin- and phospholipid-interacting proteins; a common potential binding motif was identified for many of the calmodulin-binding proteins. Thus, microarrays of an entire eukaryotic proteome can be prepared and screened for diverse biochemical activities. The microarrays can also be used to screen protein-drug interactions and to detect posttranslational modifications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhu, H -- Bilgin, M -- Bangham, R -- Hall, D -- Casamayor, A -- Bertone, P -- Lan, N -- Jansen, R -- Bidlingmaier, S -- Houfek, T -- Mitchell, T -- Miller, P -- Dean, R A -- Gerstein, M -- Snyder, M -- New York, N.Y. -- Science. 2001 Sep 14;293(5537):2101-5. Epub 2001 Jul 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11474067" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Amino Acid Sequence ; Calmodulin/metabolism ; Calmodulin-Binding Proteins/metabolism ; Cell Membrane/metabolism ; Cloning, Molecular ; Fungal Proteins/chemistry/genetics/*metabolism ; Glucose/metabolism ; Liposomes/metabolism ; Membrane Proteins/metabolism ; Molecular Sequence Data ; Open Reading Frames ; Peptide Library ; Phosphatidylcholines/metabolism ; Phosphatidylinositols/metabolism ; Phospholipids/metabolism ; Protein Binding ; *Proteome ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Signal Transduction ; Streptavidin/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2002-01-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerstein, Mark -- Lan, Ning -- Jansen, Ronald -- New York, N.Y. -- Science. 2002 Jan 11;295(5553):284-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. mark.gerstein@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11786630" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; *Computational Biology ; Databases, Genetic ; Databases, Protein ; Gene Expression Profiling ; Genome ; Genome, Fungal ; *Genomics ; Humans ; Peptide Library ; Protein Structure, Tertiary ; Proteins/*chemistry/*metabolism ; *Proteome ; Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Two-Hybrid System Techniques
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerstein, M -- Chothia, C -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1682-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biophysics and Biochemistry Department, Yale University, New Haven, CT 06520, USA. mark.gerstein@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523185" target="_blank"〉PubMed〈/a〉
    Keywords: Aspartic Acid/metabolism ; Bacterial Physiological Phenomena ; Bacteriorhodopsins/chemistry/metabolism ; Binding Sites ; Cell Membrane/chemistry/*metabolism ; Chemotaxis ; Crystallography, X-Ray ; Dimerization ; Electron Spin Resonance Spectroscopy ; Membrane Proteins/chemistry/metabolism ; Models, Biological ; Protein Conformation ; Protein Structure, Secondary ; Receptors, Amino Acid/*chemistry/*metabolism ; Receptors, Nicotinic/chemistry/metabolism ; *Signal Transduction ; Solubility
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2008-06-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sasidharan, Rajkumar -- Gerstein, Mark -- England -- Nature. 2008 Jun 5;453(7196):729-31. doi: 10.1038/453729a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18528383" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*genetics/metabolism ; Mice ; Pseudogenes/*genetics ; RNA Helicases/metabolism ; RNA Interference ; RNA, Small Interfering/biosynthesis/genetics/*metabolism ; RNA-Induced Silencing Complex/metabolism ; Retroelements/genetics ; Ribonuclease III
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seringhaus, Michael -- Gerstein, Mark -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):40-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204626" target="_blank"〉PubMed〈/a〉
    Keywords: Bibliometrics ; Chemical Phenomena ; *Chemistry ; Crystallography ; Molecular Structure ; *Nobel Prize ; Protein Conformation ; PubMed
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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