Abstract：
:As large-scale re-sequencing of genomes reveals many protein mutations, especially in human cancer tissues, prediction of their likely functional impact becomes important practical goal. Here, we introduce a new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns. The information in these patterns is derived from aligned families and sub-families of sequence homologs within and between species using combinatorial entropy formalism. The score performs well on a large set of human protein mutations in separating disease-associated variants (∼19 200), assumed to be strongly functional, from common polymorphisms (∼35 600), assumed to be weakly functional (area under the receiver operating characteristic curve of ∼0.86). In cancer, using recurrence, multiplicity and annotation for ∼10 000 mutations in the COSMIC database, the method does well in assigning higher scores to more likely functional mutations ('drivers'). To guide experimental prioritization, we report a list of about 1000 top human cancer genes frequently mutated in one or more cancer types ranked by likely functional impact; and, an additional 1000 candidate cancer genes with rare but likely functional mutations. In addition, we estimate that at least 5% of cancer-relevant mutations involve switch of function, rather than simply loss or gain of function.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Reva B,Antipin Y,Sander Cdoi
10.1093/nar/gkr407subject
Has Abstractpub_date
2011-09-01 00:00:00pages
e118issue
17eissn
0305-1048issn
1362-4962pii
gkr407journal_volume
39pub_type
杂志文章abstract：:The beta-globin gene of a patient with mRNA-deficient beta o-thalassemia has been sequenced. We find a single nucleotide deletion in amino acid codon 44 that produces a UGA terminator at codon 60. We have previously shown that the beta-globin mRNA of this patient is correctly spliced and polyadenylated, but rapidly tu...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/10.18.5421
更新日期：1982-09-25 00:00:00
abstract：:Recently, due to the dual roles of DNA and enzyme, DNAzyme has been widely used in the field of DNA circuit, which has a wide range of applications in bio-engineered system, information processing and biocomputing. In fact, the activity of DNAzymes was regulated by subunits assembly, pH control and metal ions triggers...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gky1245
更新日期：2019-02-20 00:00:00
abstract：:Mutations in the RecQ DNA helicase gene BLM give rise to Bloom's syndrome, which is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition. BLM helicase is highly active in binding and unwinding G-quadruplexes (G4s), which are physiological targets for BLM, as revealed by ge...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv361
更新日期：2015-05-19 00:00:00
abstract：:We show herein the transcription of a processed gene that originated from a spliced transcript. Recently, we isolated the human and murine homologues of the yeast chromatin protein, SPT4. The Supt4h gene is spliced normally from five exons encoded by chromosome 11. Here we show that a related sequence on chromosome 10...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.21.4960
更新日期：1998-11-01 00:00:00
abstract：:The crystal structure of d(CATGGGCCCATG)(2) shows unique stacking patterns of a stable B<-->A-DNA intermediate. We evaluated intrinsic base stacking energies in this crystal structure using an ab initio quantum mechanical method. We found that all crystal base pair steps have stacking energies close to their values in...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.24.4893
更新日期：2000-12-15 00:00:00
abstract：:50 to 55% of tobacco and barley nuclear DNA is accessible to micrococcal endonuclease digestion. The DNA fragments resulting from a mild endonuclease treatment are multiples of a basic unit of 194 +/- 6 base pairs in tobacco and 195 +/- 6 base pairs in barley. After extensive digestion, a DNA fragment of approximately...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/4.10.3617
更新日期：1977-10-01 00:00:00
abstract：:Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interacti...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkx1011
更新日期：2018-01-04 00:00:00
abstract：:Genetic screens in Saccharomyces cerevisiae have identified the roles of ribosome components, tRNAs and translation factors in translational fidelity. These screens rely on the suppression of altered start codons, nonsense codons or frameshift mutations in genes involved in amino acid or nucleotide metabolism. Many of...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gki765
更新日期：2005-08-12 00:00:00
abstract：:Eight base analogs were tested as third strand residues in otherwise homopyrimidine strands opposite each of the 'direct' (A.T and G.C) and 'inverted' (T.A and C.G) Watson-Crick base pairs, using UV melting profiles to assess triplex stability. The target duplexes contained 20 A.T base pairs and a central test base pa...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/27.23.4632
更新日期：1999-12-01 00:00:00
abstract：:A physical map is presented for the 1200 kb genome of Mycoplasma mycoides subsp. mycoides Y, locating 32 cleavage sites for 8 restriction endonucleases. The large restriction fragments involved were separated and sized by pulsed-field agarose gel electrophoresis. Their locations on the map were determined by probing S...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.13.6027
更新日期：1988-07-11 00:00:00
abstract：:The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are ...
journal_title：Nucleic acids research
pub_type： 杂志文章,评审
doi：10.1093/nar/gkaa261
更新日期：2020-05-21 00:00:00
abstract：:A DNA copy of influenza A/NT/60/68 viral RNA segment 2, corresponding to protein P1, has been cloned in the E.coli plasmid pBr322. The clone is 2341 nucleotides long and represents a full-length copy of the viral RNA. In the viral complementary (plus sense) strand there is an open reading frame that is 2271 nucleotide...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/10.4.1335
更新日期：1982-02-25 00:00:00
abstract：:The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) is a member of a sub-family of phosphatidylinositol (PI) 3-kinases termed PIK-related kinases. A distinguishing feature of this sub-family is the presence of a conserved C-terminal region downstream of a PI 3-kinase domain. Mutants defective in DNA-P...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.8.1965
更新日期：1998-04-15 00:00:00
abstract：:The strand displacement activity of DNA polymerase δ is strongly stimulated by its interaction with proliferating cell nuclear antigen (PCNA). However, inactivation of the 3'-5' exonuclease activity is sufficient to allow the polymerase to carry out strand displacement even in the absence of PCNA. We have examined in ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv260
更新日期：2015-04-30 00:00:00
abstract：:Regulation of gene transcription in both prokaryotes and eukaryotes involves formation of various DNA-multiprotein complexes of higher order structure through communication between distant regions of DNA. The communication between distant DNA sites occurs by interaction between proteins bound to the sites by looping o...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/25.4.873
更新日期：1997-02-15 00:00:00
abstract：:This article presents W-IQ-TREE, an intuitive and user-friendly web interface and server for IQ-TREE, an efficient phylogenetic software for maximum likelihood analysis. W-IQ-TREE supports multiple sequence types (DNA, protein, codon, binary and morphology) in common alignment formats and a wide range of evolutionary ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw256
更新日期：2016-07-08 00:00:00
abstract：:IStrons are chimeric genetic elements composed of a group I intron associated with an insertion sequence (IS). The group I intron is a catalytic RNA providing the IStron with self-splicing ability, which renders IStron insertions harmless to the host genome. The IS element is a DNA transposon conferring mobility, and ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku939
更新日期：2014-11-10 00:00:00
abstract：:Segments of SV40 DNA having homologous overlapping termini recombine to produce viable genomes in monkey cells. Frequencies of recombination on either side of a deletion marker are non-random; replication and palindromes do not appear to be essential. Since recombination involves host enzymes, a suitable system has be...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/8.12.2725
更新日期：1980-06-25 00:00:00
abstract：:The precursor to the Euglena light harvesting chlorophyll a/b binding protein of photosystem II (LHCPII) is a polyprotein containing multiple copies of LHCPII covalently joined by a decapeptide linker. cDNA and genomic clones encoding the 5' and 3' end of a 6.6 kb LHCPII mRNA were sequenced. A 3.1 kb genomic region en...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.25.5737
更新日期：1994-12-25 00:00:00
abstract：:Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku303
更新日期：2014-06-01 00:00:00
abstract：:Chinese hamster genomic DNA sequences from the region downstream of the dihydrofolate reductase (DHFR) gene reported to contain a chromosomal origin of bidirectional DNA replication (OBR-1) were tested for their ability to support autonomous DNA replication in human cells. A 13.3 kilobase fragment containing OBR-1 and...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/20.22.5971
更新日期：1992-11-25 00:00:00
abstract：:Transcription and mRNA export are linked processes. However, the molecular mechanisms of this coordination are not clear. Sus1 (hENY2) participates in this coordination as part of two protein complexes: SAGA, a transcriptional co-activator; TREX-2, which functions in mRNA biogenesis and export. Here, we investigate th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt272
更新日期：2013-06-01 00:00:00
abstract：:During protein synthesis, ribosomes become stalled on polyproline-containing sequences, unless they are rescued in archaea and eukaryotes by the initiation factor 5A (a/eIF-5A) and in bacteria by the homologous protein EF-P. While a structure of EF-P bound to the 70S ribosome exists, structural insight into eIF-5A on ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv1517
更新日期：2016-02-29 00:00:00
abstract：:The DNA sequence of the spacer (plus flanking) regions separating the 16S rRNA and 23S rRNA genes of two presumptive rDNA operons of the archaebacterium Methanococcus vannielii was determined. The spacers are 156 and 242 base pairs in size and they share a sequence homology of 49 base pairs following the 3' terminus o...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/11.21.7537
更新日期：1983-11-11 00:00:00
abstract：:The MyHits web site (http://myhits.isb-sib.ch) is an integrated service dedicated to the analysis of protein sequences. Since its first description in 2004, both the user interface and the back end of the server were improved. A number of tools (e.g. MAFFT, Jacop, Dotlet, Jalview, ESTScan) were added or updated to imp...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm352
更新日期：2007-07-01 00:00:00
abstract：:The paper describes an improved method for the synthesis of oligodeoxyribonucleotides using phosphoramidite chemistry. Our procedure relies on novel phosphoramidite intermediates, the deoxyribonucleoside-3'-morpholine-methoxyphosphins. These compounds are extremely stable and can be purified readily. Condensation reac...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/11.9.2575
更新日期：1983-05-11 00:00:00
abstract：:Small interfering RNAs (siRNAs) are promising new active compounds in gene medicine but the induction of non-specific immune responses following their delivery continues to be a serious problem. With the purpose of avoiding such effects chemically modified siRNAs are tested in screening assay but often only examining ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks033
更新日期：2012-05-01 00:00:00
abstract：:The nucleolus is a unique structural component of interphase nuclei where the ribosomal genes, trans-cribed by RNA polymerase I (RNA pol I), are organized. In the present study, the repair of UV-induced photolesions was investigated in the ribosomal DNA (rDNA) in relation to RNA pol I transcription. We used hamster ce...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/27.12.2511
更新日期：1999-06-15 00:00:00
abstract：:RNA polymerase III recognizes and pauses at its terminator, an oligo(dT) tract in non-template DNA, terminates 3' oligo(rU) synthesis within this sequence, and releases the RNA. The pol III subunit Rpc11p (C11) mediates RNA 3'-5' cleavage in the catalytic center of pol III during pausing. The amino and carboxyl region...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr182
更新日期：2011-08-01 00:00:00
abstract：:The delivery of site-specific post-translational modifications to histones generates an epigenetic regulatory network that directs fundamental DNA-mediated processes and governs key stages in development. Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stabilit...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt776
更新日期：2014-01-01 00:00:00
