Abstract:
:The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Nguyen DT,Mathias S,Bologa C,Brunak S,Fernandez N,Gaulton A,Hersey A,Holmes J,Jensen LJ,Karlsson A,Liu G,Ma'ayan A,Mandava G,Mani S,Mehta S,Overington J,Patel J,Rouillard AD,Schürer S,Sheils T,Simeonov A,Sklar Ldoi
10.1093/nar/gkw1072subject
Has Abstractpub_date
2017-01-04 00:00:00pages
D995-D1002issue
D1eissn
0305-1048issn
1362-4962pii
gkw1072journal_volume
45pub_type
杂志文章abstract::Nucleobase analogs 5-methylisocytosine ((Me)isoC) and isoguanine (isoG) form a non-natural base pair in duplex nucleic acids with base pairing specificity orthogonal to the natural nucleobase pairs. Sequencing reactions were conducted with oligodeoxyribonucleotides (ODNs) containing d(Me)isoC and disoG using modified ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki628
更新日期:2005-06-02 00:00:00
abstract::E. coli can be transformed to extremely high efficiencies by subjecting a mixture of cells and DNA to brief but intense electrical fields of exponential decay waveform (electroporation). We have obtained 10(9) to 10(10) transformants/micrograms with strains LE392 and DH5 alpha, and plasmids pUC18 and pBR329. The proce...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.13.6127
更新日期:1988-07-11 00:00:00
abstract::An improved contact hybridization technique for the analysis of labelled RNA species is presented. The method combines high sensitivity of detection with the high resolution of polyacrylamide gel electrophoresis and should be especially useful for the characterization of transient RNA precursor molecules. Its applicat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.9.2963
更新日期:1979-07-11 00:00:00
abstract::The interaction of antibodies directed toward N6-(delta2-isopentenyl)adenosine, i6Ado, or its nucleotide with related bases, nucleosides, nucleotides and purified tRNAs is described. The selectivity of the antibody preparation was tested in inhibition experiments utilizing a sensitive radioimmunoassay to quantitate th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.9.3439
更新日期:1978-09-01 00:00:00
abstract::This paper presents TurboFold II, an extension of the TurboFold algorithm for predicting secondary structures for multiple RNA homologs. TurboFold II augments the structure prediction capabilities of TurboFold by additionally providing multiple sequence alignments. Probabilities for alignment of nucleotide positions b...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx815
更新日期:2017-11-16 00:00:00
abstract::The U1 snRNP-specific 70K protein is one of the few snRNP proteins from higher eukaryotic cells that is phosphorylated in vivo (1,2). Immunoaffinity purified spliceosomal snRNPs (U1, U2, U5, and U4/U6) were tested for their ability to phosphorylate in vitro the U1-specific 70K protein. An snRNP-associated kinase activ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.12.2815
更新日期:1993-06-25 00:00:00
abstract::Cisplatin analogues were synthesised that consisted of platinum(II) diamine complexes tethered via a polymethylene chain ( n = 3, 5, 8 and 10) to a phenanthridinium cation. Both chloro and iodo leaving groups were examined. DNA adduct formation was quantitatively analysed using a linear amplification system with the p...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.17.3933
更新日期:1998-09-01 00:00:00
abstract::We previously reported the isolation of PRP28, a gene in Saccharomyces cerevisiae whose activity is required for the first step of nuclear mRNA splicing in vivo. Sequence analysis revealed that PRP28 is included in the 'DEAD-box' gene family, members of which are thought to function as ATP-dependent RNA helicases. Gen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.15.3187
更新日期:1994-08-11 00:00:00
abstract::Chromatin core particles near physiological ionic strength undergo a reversible transition induced by changes in pH near neutrality. While sedimentation studies indicate no significant effect on size or shape, changes in tyrosine fluorescence anisotropy and in circular dichroism suggest a somewhat looser structure at ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.10.4351
更新日期:1984-05-25 00:00:00
abstract::In order to characterize structure-function relationships, the kinetic behavior of chimeric RNA/DNA ribozyme was compared with that of all RNA ribozyme. Determined kcat values were proven to represent the chemical-cleavage step and not the product-dissociation step. In agreement with the finding by Dahm and Uhlenbeck ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.24.5656
更新日期:1993-12-11 00:00:00
abstract::Genome length complementary DNA (cDNA) transcripts were synthesized in vitro by using purified virions of a cloned isolate of mouse sarcoma virus (MSV Clone 124). The cDNA transcripts were converted to double-stranded form by utilizing DNase-digested calf thymus DNA primers and E. coli DNA polymerase I. Restriction en...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.5.1863
更新日期:1979-01-01 00:00:00
abstract::We have characterized triple-helix-mediated inhibition of an artificial bacteriophage promoter with respect to relief of inhibition by incoming RNA polymerases that initiate upstream or downstream from the operator sequence. Whereas oligonucleotide-directed triple-helix formation inhibits the test promoter, promoter a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.17.4055
更新日期:1993-08-25 00:00:00
abstract::We have examined the formation of alternate strand triple-helices at the target sequence A11(TC)6.(GA)6T11 using the oligonucleotides T11(AG)6 and T11(TG)6, by DNase I footprinting. These third strands were designed so as to form parallel T.AT triplets together with antiparallel G.GC and A.AT or T.AT triplets. We find...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.19.3977
更新日期:1994-09-25 00:00:00
abstract::Post-synthetic enzymatic hypermethylation of DNA was induced in hamster fibrosarcoma cells by the DNA synthesis inhibitors cytosine arabinoside, hydroxyurea and aphidicolin. This effect required direct inhibition of DNA polymerase alpha or reduction in deoxynucleotide pools and was not specific to a single cell type. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.10.4353
更新日期:1986-05-27 00:00:00
abstract::Sequence-specific binding of proteins to their DNA targets involves a complex spectrum of processes that often induce DNA conformational variation in the bound complex. The forces imposed by protein binding that cause the helical deformations are intimately interrelated and difficult to parse or rank in importance. To...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt492
更新日期:2013-08-01 00:00:00
abstract::The molecular mechanisms that underlie the neurological manifestations of patients with inherited diseases of vitamin B12 (cobalamin) metabolism remain to date obscure. We observed transcriptomic changes of genes involved in RNA metabolism and endoplasmic reticulum stress in a neuronal cell model with impaired cobalam...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky634
更新日期:2018-09-06 00:00:00
abstract::The Gene Expression Database (GXD) is a community resource of gene expression information for the laboratory mouse. By combining the different types of expression data, GXD aims to provide increasingly complete information about the expression profiles of genes in different mouse strains and mutants, thus enabling val...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.1.98
更新日期:2001-01-01 00:00:00
abstract::The recognition of human tRNA(Leu) or tRNA(Ser) by cognate aminoacyl- tRNA synthetases has distinct requirements. Only one base change (A73-->G) in tRNA(Leu) is required to generate an efficient serine acceptor in vitro, whereas several changes in three structural domains (the acceptor stem, DHU loop and long extra ar...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.3.405
更新日期:1996-02-01 00:00:00
abstract::On the tandemly linked ribosomal genes of Xenopus laevis, the RNA polymerase transcribes past the 3' end of the 40S coding region and terminates at T3 just upstream of the gene promoter. The close proximity of T3 to the gene promoter, and the functional interdependence of these two elements, has led to the suggestion ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.1.373
更新日期:1989-01-11 00:00:00
abstract::Guanine rich nucleic acid sequences can form G-quadruplex (G4) structures that interfere with DNA replication, repair and RNA transcription. The human FANCJ helicase contributes to maintaining genomic integrity by promoting DNA replication through G4-forming DNA regions. Here, we combined single-molecule and ensemble ...
journal_title:Nucleic acids research
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更新日期:2016-10-14 00:00:00
abstract::The Deciphering the Mechanisms of Developmental Disorders (DMDD) consortium is a research programme set up to identify genes in the mouse, which if mutated (or knocked-out) result in embryonic lethality when homozygous, and initiate the study of why disruption of their function has such profound effects on embryo deve...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:1984-11-12 00:00:00
abstract::Yaf9 is an integral part of the NuA4 acetyltransferase and the SWR1 chromatin remodeling complexes. Here, we show that Yaf9 associates with acetylated histone H3 with high preference for H3K27ac. The crystal structure of the Yaf9 YEATS domain bound to the H3K27ac peptide reveals that the sequence C-terminal to K27ac s...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1151
更新日期:2018-01-09 00:00:00
abstract::Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from many phyla. Pnkp is composed of three catalytic modules: an N-terminal polynucleotide 5' kinase, a central 2',3' phosphatase and a C-terminal ligase. The phosphatase module is a Mn(2+)-dependent phosphodiesterase...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt221
更新日期:2013-06-01 00:00:00
abstract::Large-scale cooperative helix opening has been previously observed in A + T rich sequences contained in supercoiled DNA molecules at elevated temperatures. Since it is well known that helix melting of linear DNA is suppressed by addition of salt, we have investigated the effects of added salts on opening transitions i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.11.2042
更新日期:1994-06-11 00:00:00
abstract::Dnmt3a and Dnmt3b are paralogous enzymes responsible for de novo DNA methylation but with distinguished biological functions. In mice, disruption of Dnmt3b but not Dnmt3a causes global DNA hypomethylation, especially in repetitive sequences, which comprise the large majority of methylated DNA in the genome. By measuri...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq456
更新日期:2010-10-01 00:00:00
abstract::The history and mechanism of molecular evolution in DNA have been greatly elucidated by contributions from genetics, probability theory and bioinformatics--indeed, mathematical developments such as Kimura's neutral theory, Kingman's coalescent theory and efficient software such as BLAST, ClustalW, Phylip, etc., provid...
journal_title:Nucleic acids research
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更新日期:2009-07-01 00:00:00
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journal_title:Nucleic acids research
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更新日期:2021-01-25 00:00:00
abstract::A correlation between histone acetylation and transcription has been noted for a long time, but little is known about what step(s) in the transcription cycle is influenced by acetylation. We have examined the immediate transcriptional response to histone deacetylase (HDAC) inhibition, and find that release of promoter...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa234
更新日期:2020-05-21 00:00:00
abstract::The Immune Epitope Database Analysis Resource (IEDB-AR, http://tools.iedb.org/) is a companion website to the IEDB that provides computational tools focused on the prediction and analysis of B and T cell epitopes. All of the tools are freely available through the public website and many are also available through a RE...
journal_title:Nucleic acids research
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更新日期:2019-07-02 00:00:00