Abstract:
:One of the obstacles hindering a better understanding of cancer is its heterogeneity. However, computational approaches to model cancer heterogeneity have lagged behind. To bridge this gap, we have developed a new probabilistic approach that models individual cancer cases as mixtures of subtypes. Our approach can be seen as a meta-model that summarizes the results of a large number of alternative models. It does not assume predefined subtypes nor does it assume that such subtypes have to be sharply defined. Instead given a measure of phenotypic similarity between patients and a list of potential explanatory features, such as mutations, copy number variation, microRNA levels, etc., it explains phenotypic similarities with the help of these features. We applied our approach to Glioblastoma Multiforme (GBM). The resulting model Prob_GBM, not only correctly inferred known relationships but also identified new properties underlining phenotypic similarities. The proposed probabilistic framework can be applied to model relations between similarity of gene expression and a broad spectrum of potential genetic causes.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Cho DY,Przytycka TMdoi
10.1093/nar/gkt577subject
Has Abstractpub_date
2013-09-01 00:00:00pages
8011-20issue
17eissn
0305-1048issn
1362-4962pii
gkt577journal_volume
41pub_type
杂志文章abstract::An intronic hexanucleotide UGCAUG has been shown to play a critical role in the regulation of tissue-specific alternative splicing of pre-mRNAs in a wide range of tissues. Vertebrate Fox-1 has been shown to bind to this element, in a highly sequence-specific manner, through its RNA recognition motif (RRM). In mammals,...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki338
更新日期:2005-04-11 00:00:00
abstract::The primary rRNA transcript contains a large external transcribed spacer (ETS) approximately 4,000 nucleotides in length. We have used subcloned DNA probes derived from the 5' end of the ETS in conjunction with Northern blot analysis of murine nuclear RNA to examine processing of this region. In agreement with the res...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.18.7187
更新日期:1984-09-25 00:00:00
abstract::DNA methylation, the most intensively studied epigenetic modification, plays an important role in understanding the molecular basis of diseases. Furthermore, epigenome-wide association study (EWAS) provides a systematic approach to identify epigenetic variants underlying common diseases/phenotypes. However, there is n...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky942
更新日期:2019-01-08 00:00:00
abstract::A novel class of RNA-binding proteins, Puf, regulates translation and RNA stability by binding to specific sequences in the 3'-untranslated region of target mRNAs. Members of this protein family share a conserved Puf domain consisting of eight 36 amino acid imperfect repeats. Here we report two Puf family member genes...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkf600
更新日期:2002-11-01 00:00:00
abstract::The viral RNA (vRNA) genome of influenza viruses is replicated by the RNA-dependent RNA polymerase (RNAP) via a complementary RNA (cRNA) intermediate. The vRNA promoter can adopt multiple conformations when bound by the RNAP. However, the dynamics, determinants, and biological role of these conformations are unknown; ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz313
更新日期:2019-07-09 00:00:00
abstract::IHF and HU are two heterodimeric nucleoid-associated proteins (NAP) that belong to the same protein family but interact differently with the DNA. IHF is a sequence-specific DNA-binding protein that bends the DNA by over 160°. HU is the most conserved NAP, which binds non-specifically to duplex DNA with a particular pr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr1236
更新日期:2012-04-01 00:00:00
abstract::The histone variant H2A.Z has been implicated in many biological processes, such as gene regulation and genome stability. Here, we present the identification of H2A.Z.2.2 (Z.2.2), a novel alternatively spliced variant of histone H2A.Z and provide a comprehensive characterization of its expression and chromatin incorpo...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks267
更新日期:2012-07-01 00:00:00
abstract::We used 2D protein gel electrophoresis and DNA microarray technologies to systematically analyze genes under glucose repression in B:acillus subtilis. In particular, we focused on genes expressed after the shift from glycolytic to gluconeogenic at the middle logarithmic phase of growth in a nutrient sporulation medium...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.3.683
更新日期:2001-02-01 00:00:00
abstract::A synapomorphy is a phylogenetic character that provides evidence of shared descent. Ideally a synapomorphy is ubiquitous within the clade of related organisms and nonexistent outside the clade, implying that it arose after divergence from other extant species and before the last common ancestor of the clade. With the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl440
更新日期:2006-01-01 00:00:00
abstract::GGRNA (http://GGRNA.dbcls.jp/) is a Google-like, ultrafast search engine for genes and transcripts. The web server accepts arbitrary words and phrases, such as gene names, IDs, gene descriptions, annotations of gene and even nucleotide/amino acid sequences through one simple search box, and quickly returns relevant Re...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks448
更新日期:2012-07-01 00:00:00
abstract::The linking number of DNA in minichromosomes increases by 2 turns during SV40 assembly. Changes in temperature also influence the average linking number of the total intracellular forms of SV40 DNA. When the isolated minichromosomes assembled in vivo are incubated with topoisomerase I at 33 degrees C in vitro, the lin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.9.3703
更新日期:1987-05-11 00:00:00
abstract::PRMT5 is an arginine methyltransferase that accounts for the vast majority of the symmetric methylation in cells. PRMT5 exerts its function when complexed with MEP50/WDR77. This activity is often elevated in cancer cells and correlates with poor prognosis, making PRMT5 a therapeutic target. To investigate the PRMT5 si...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz200
更新日期:2019-06-04 00:00:00
abstract::Transcription of RNA from the beta-globin (major) gene in nuclei from induced mouse erythroleukemia cells terminates within the region between 700 to 2000 bases downstream from the poly(A) addition site, but not at particularly favored sites. In addition we present the first analysis of in vivo labeled RNA from a cell...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.22.8723
更新日期:1984-11-26 00:00:00
abstract::A direct correlation exists between the level of histone H4 hyperacetylation induced by sodium butyrate and the extent to which nucleosomes lose their compact shape and become elongated (62.0% of the particles have a length/width ratio over 1.6; overall mean in the length/width ratio = 1.83 +/- 0.48) when bound to ele...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.9.2739
更新日期:1990-05-11 00:00:00
abstract::Various antitumor drugs stabilize DNA topoisomerase II-DNA transient covalent complexes. The complexes distribution along pBR322 DNA was shown previously to depend upon the nature of the drug (Tewey et al. (1984) Science 226, 466-468). The position in pBR322 of DNA cleavage by calf DNA topoisomerase II for 115 such si...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.11.2861
更新日期:1991-06-11 00:00:00
abstract::Homing endonucleases recognize long target DNA sequences generating an accurate double-strand break that promotes gene targeting through homologous recombination. We have modified the homodimeric I-CreI endonuclease through protein engineering to target a specific DNA sequence within the human RAG1 gene. Mutations in ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq801
更新日期:2011-01-01 00:00:00
abstract::We have detected a set of transcripts in Drosophila melanogaster cells which are homologous to repeating elements within the 'non-transcribed' spacer region of rDNA. The RNA molecules range from 240 to 1680 nucleotides, differing in length by an integral value of 240 nucleotides. We have sequenced several AluI fragmen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.1.11
更新日期:1983-01-11 00:00:00
abstract::The rolling circle DNA replication structures generated by the in vitro phage T4 replication system were analyzed using two-dimensional agarose gels. Replication structures were generated in the presence or absence of T4 primase (gp61), permitting the analysis of replication forks with either duplex or single-stranded...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.11.2166
更新日期:1996-06-01 00:00:00
abstract::This work presents the Apo-Holo DataBase (AH-DB, http://ahdb.ee.ncku.edu.tw/ and http://ahdb.csbb.ntu.edu.tw/), which provides corresponding pairs of protein structures before and after binding. Conformational transitions are commonly observed in various protein interactions that are involved in important biological f...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr940
更新日期:2012-01-01 00:00:00
abstract::A previously elaborated technique for fixing a chosen partially melted state of DNA with glyoxal was used in a study of the melting process of the replicative form (RF III) of phi X174 DNA. Electron-microscopic maps corresponding to five points of the melting curve of RF III were obtained and compared with the theoret...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.6.1867
更新日期:1982-03-25 00:00:00
abstract::Structural Maintenance of Chromosomes (SMC) proteins are vital for a wide range of processes including chromosome structure and dynamics, gene regulation and DNA repair. Eukaryotes have three SMC complexes, consisting of heterodimeric pairs of six different SMC proteins along with several specific regulatory subunits....
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq038
更新日期:2010-06-01 00:00:00
abstract::A new method for specific reamplification of DDRT-PCR products is presented. After transient ligation of the primary DDRT-PCR fragments into a T-vector, the cDNAs of interest were reamplified by hemi-nested PCR and thermally asymmetric cycles. In contrast to the originally described protocol, this method of reamplific...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.4.1130
更新日期:1998-02-15 00:00:00
abstract::The structure of eukaryotic chromatin has been investigated by isolating and analyzing the "accessible" DNA fraction of rat liver chromatin. This DNA fraction has been isolated by titrating the chromatin with the protese-resistant D isomer of polylysine to bind the "accessible" DNA sites. After removal of chromosomal ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/2.5.667
更新日期:1975-05-01 00:00:00
abstract::RNase E is a 472-kDa homo-tetrameric essential endoribonuclease involved in RNA processing and turnover in Escherichia coli. In its N-terminal half (NTH) is the catalytic active site, as also a substrate 5'-sensor pocket that renders enzyme activity maximal on 5'-monophosphorylated RNAs. The protein's non-catalytic C-...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz1152
更新日期:2020-01-24 00:00:00
abstract::Signals setting the level of transcription of the tRNA-tufB operon have been studied by deletion mapping. TufB transcription was measured in vivo with plasmid-borne tRNA-tufB:galk operon fusions. Removal of the sequences from -133 to -58 with respect to the transcription start point, results in a 90% decrease of tufB ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.22.9515
更新日期:1987-11-25 00:00:00
abstract::Puromycin, an analog of the 3' end of aminoacyl-tRNA, causes premature termination of translation by being linked non-specifically to growing polypeptide chains. Here we report the interesting phenomenon that puromycin acting as a non-inhibitor at very low concentration (e.g. 0.04 microM) can bond only to full-length ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.5.1176
更新日期:2000-03-01 00:00:00
abstract::UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is subsequently recognized by DNMT1 to promote its localization onto repli...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky104
更新日期:2018-04-06 00:00:00
abstract::The role of Ribonuclease H1 (RNase H1) during primer removal and ligation at the mitochondrial origin of light-strand DNA synthesis (OriL) is a key, yet poorly understood, step in mitochondrial DNA maintenance. Here, we reconstitute the replication cycle of L-strand synthesis in vitro using recombinant mitochondrial p...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky708
更新日期:2018-10-12 00:00:00
abstract::Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw979
更新日期:2017-02-17 00:00:00
abstract::The Cox protein from bacteriophage P2 forms oligomeric filaments and it has been proposed that DNA can be wound up around these filaments, similar to how histones condense DNA. We here use fluorescence microscopy to study single DNA-Cox complexes in nanofluidic channels and compare how the Cox homologs from phages P2 ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw352
更新日期:2016-09-06 00:00:00