Abstract:
:Genome-wide transcriptome profiling has enabled non-supervised classification of tumours, revealing different sub-groups characterized by specific gene expression features. However, the biological significance of these subtypes remains for the most part unclear. We describe herein an interactive platform, Minimum Spanning Trees Inferred Clustering (MiSTIC), that integrates the direct visualization and comparison of the gene correlation structure between datasets, the analysis of the molecular causes underlying co-variations in gene expression in cancer samples, and the clinical annotation of tumour sets defined by the combined expression of selected biomarkers. We have used MiSTIC to highlight the roles of specific transcription factors in breast cancer subtype specification, to compare the aspects of tumour heterogeneity targeted by different prognostic signatures, and to highlight biomarker interactions in AML. A version of MiSTIC preloaded with datasets described herein can be accessed through a public web server (http://mistic.iric.ca); in addition, the MiSTIC software package can be obtained (github.com/iric-soft/MiSTIC) for local use with personalized datasets.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Lemieux S,Sargeant T,Laperrière D,Ismail H,Boucher G,Rozendaal M,Lavallée VP,Ashton-Beaucage D,Wilhelm B,Hébert J,Hilton DJ,Mader S,Sauvageau Gdoi
10.1093/nar/gkx338subject
Has Abstractpub_date
2017-07-27 00:00:00pages
e122issue
13eissn
0305-1048issn
1362-4962pii
3796331journal_volume
45pub_type
杂志文章abstract::The human immunodeficiency virus (HIV) and other retroviruses show extensive genomic variation, which is primarily due to error-prone replication by the viral reverse transcriptase (RT) enzymes. RT errors include misincorporation with subsequent extension of the mismatched terminal base, and extension of realigned pri...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.8.1319
更新日期:1995-04-25 00:00:00
abstract::Polyadenylation of nascent transcripts is one of the key mRNA processing events in eukaryotic cells. A large number of human and mouse genes have alternative polyadenylation sites, or poly(A) sites, leading to mRNA variants with different protein products and/or 3'-untranslated regions (3'-UTRs). PolyA_DB 2 contains p...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl870
更新日期:2007-01-01 00:00:00
abstract::The c-myc proto-oncogene encodes a highly unstable mRNA. Stabilized, truncated myc transcripts have been found in several human and murine tumors of hematopoietic origin. Recently, two tumors expressing 3' truncated c-myc mRNAs that were five times more stable than normal myc transcripts, were described. We have tried...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.9.2387
更新日期:1991-05-11 00:00:00
abstract::We have implemented a genome annotation system for prokaryotes called AGMIAL. Our approach embodies a number of key principles. First, expert manual annotators are seen as a critical component of the overall system; user interfaces were cyclically refined to satisfy their needs. Second, the overall process should be o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl471
更新日期:2006-07-19 00:00:00
abstract::The original cDNA sequence reported for the murine DNA methyltransferase (MTase) was not full length. Recently, additional cDNA sequences have been reported that lie upstream of the original and contain an extended open reading frame with three additional ATGs in frame with the coding region [Tucker et al . (1996) Pro...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.22.4666
更新日期:1997-11-15 00:00:00
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...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1072
更新日期:2017-01-04 00:00:00
abstract::The Escherichia coli AlkB protein catalyzes the direct reversal of alkylation damage to DNA; primarily 1-methyladenine (1mA) and 3-methylcytosine (3mC) lesions created by endogenous or environmental alkylating agents. AlkB is a member of the non-heme iron (II) alpha-ketoglutarate-dependent dioxygenase superfamily, whi...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1031
更新日期:2007-01-01 00:00:00
abstract::Light-inducible systems allow spatiotemporal control of a variety of biological activities. Here, we report newly optimized optogenetic tools to induce transcription with light in mammalian cells, using the Arabidopsis photoreceptor Flavin Kelch-repeat F-box 1 (FKF1) and its binding partner GIGANTEA (GI) as well as CR...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx804
更新日期:2017-11-16 00:00:00
abstract::The Raf-1 proto-oncogene product is a highly regulated serine/threonine kinase that functions in signal transduction downstream from growth factor receptors and upstream from nuclear proto-oncogene products. Using a transient cotransfection assay we have found that activated Raf-1 activates expression from the HIV-LTR...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.22.5229
更新日期:1993-11-11 00:00:00
abstract::The cancer drug daunomycin is an effective inhibitor of the B leads to Z transition in poly d(G-C) in 4 M NaCl. Both the rate and extent of the B leads to Z transition are decreased by the drug, as judged by equilibrium and kinetic studies. Daunomycin can, under some conditions, convert Z form DNA back to B form. Drug...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.23.8485
更新日期:1983-12-10 00:00:00
abstract::Genomic Denaturing Gradient Gel Electrophoresis (gDGGE) provides an alternative to the standard method of restriction fragment length polymorphism (RFLP) analysis for identifying polymorphic sequence variation in genomic DNA. For gDGGE, genomic DNA is cleaved by restriction enzymes, separated in a polyacrylamide gel c...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.7.1475
更新日期:1991-04-11 00:00:00
abstract::Oligonucleotide models of ribosomal RNA domains are powerful tools to study the binding and molecular recognition of antibiotics that interfere with bacterial translation. Techniques such as selective chemical modification, fluorescence labeling and mutations are cumbersome for the whole ribosome but readily applicabl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq159
更新日期:2010-07-01 00:00:00
abstract::RNA synthesis and DNA replication cease after DNA damage. We studied RNA synthesis using an in situ run-on assay and found ribosomal RNA (rRNA) synthesis was inhibited 24 h after UV light, gamma radiation or DNA cross-linking by cisplatin in human cells. Cisplatin led to accumulation of cells in S phase. Inhibition of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt502
更新日期:2013-08-01 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 developed an effective post-PCR sterilization process and have applied the procedure to a diagnostic assay for HIV-1. The method, which is based on isopsoralen photochemistry, satisfies both the inactivation and hybridization requirements of a practical sterilization process. The key feature of the technique i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.1.109
更新日期:1991-01-11 00:00:00
abstract::The binding of nine aminoalkyl adenylates to isoleucyl-tRNA synthetase from Escherichia coli MRE 600 was measured and compared with the binding of the cognate amino acids. It was found that they bind rather tightly to the enzyme, the Kd's ranging from 3.1.10(-4) M with glycinol-AMP ester to 3.7.10(-9) M with L-isoleuc...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.3.673
更新日期:1977-03-01 00:00:00
abstract::Expansions of (GAA)n repeats within the first intron of the frataxin gene reduce its expression, resulting in a hereditary neurodegenerative disorder, Friedreich's ataxia. While it is generally believed that expanded (GAA)n repeats block transcription elongation, fine mechanisms responsible for gene repression are not...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl1140
更新日期:2007-01-01 00:00:00
abstract::Human papillomavirus 16 (HPV-16), which is involved in genital carcinogenesis, contains an enhancer of transcription that is activated by cellular factors rather than by the viral E2 proteins. The activity resides on a 232 bp segment with 5 binding sites for nuclear factor 1 (NF1), 2 for AP1, and 1 for steroid recepto...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.3.465
更新日期:1990-02-11 00:00:00
abstract::The NONCODE database is an integrated knowledge database designed for the analysis of non-coding RNAs (ncRNAs). Since NONCODE was first released 3 years ago, the number of known ncRNAs has grown rapidly, and there is growing recognition that ncRNAs play important regulatory roles in most organisms. In the updated vers...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm1011
更新日期:2008-01-01 00:00:00
abstract::Aryldiazonium salts are shown to be useful as phototriggered structural probes for RNA mapping as well as for footprinting of RNA/protein interaction. In particular the yeast tRNA(Asp)/aspartyl-tRNA synthetase complex is shown to involve the variable loop face and the concave side of the L-shaped nucleic acid bound to...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/18.1.89
更新日期:1990-01-11 00:00:00
abstract::The C/D box scaRNA2 is predicted to guide specific 2'-O-methylation of U2 snRNA. In contrast to other SCARNA genes, SCARNA2 appears to be independently transcribed. By transient expression of SCARNA2-reporter gene constructs, we have demonstrated that this gene is transcribed by RNA polymerase II and that the promoter...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp988
更新日期:2010-01-01 00:00:00
abstract::In DNA of the dinoflagellate Crypthecodinium cohnii, 38% of the thymine is replaced by the modified base 5-hydroxymethyluracil, and approximately 3% of the cytosine is replaced by 5-methylcytosine. Both of the modified bases are non-randomly distributed in the DNA. Determinations of 3' nearest neighbors show that HOMe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/8.20.4709
更新日期:1980-10-24 00:00:00
abstract::The HpaR-mediated regulation of the hpa-meta operon (Pg promoter) of the 4-hydroxyphenylacetic acid catabolic pathway of Escherichia coli has been studied. The HpaR regulator was purified to homogeneity showing that it is able to bind selectively to 4-hydroxyphenylacetic, 3-hydroxyphenylacetic and 3,4-dihydroxyphenyla...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg851
更新日期:2003-11-15 00:00:00
abstract::A new integrated image analysis package with quantitative quality control schemes is described for cDNA microarray technology. The package employs an iterative algorithm that utilizes both intensity characteristics and spatial information of the spots on a microarray image for signal-background segmentation and define...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.15.e75
更新日期:2001-08-01 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::Our web server, PIZSA (http://cospi.iiserpune.ac.in/pizsa), assesses the likelihood of protein-protein interactions by assigning a Z Score computed from interface residue contacts. Our score takes into account the optimal number of atoms that mediate the interaction between pairs of residues and whether these contacts...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz368
更新日期:2019-07-02 00:00:00
abstract::The Zebrafish Information Network (ZFIN, http://zfin.org), the model organism database for zebrafish, provides the central location for curated zebrafish genetic, genomic and developmental data. Extensive data integration of mutant phenotypes, genes, expression patterns, sequences, genetic markers, morpholinos, map po...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm956
更新日期:2008-01-01 00:00:00
abstract::The SRPDB (signal recognition particle database) provides annotated SRP RNA sequences from Eucaryotes and Archaea, phylogenetically ordered and aligned with their bacterial equivalents. We also make available representative RNA secondary structure diagrams, where each base pair is proven by comparative sequence analys...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.13.3019
更新日期:1993-07-01 00:00:00
abstract::The chemical reactivity of matched T and C bases to osmium tetroxide and hydroxylamine near mismatched and unmatched bases in a heteroduplex between two strands of DNA with multiple differences was examined. Data was available for matched bases one or two positions away from 24 mismatches. Reactive bases were found ne...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/17.11.4223
更新日期:1989-06-12 00:00:00
abstract::The mitochondrial DNA (mtDNA) control regions for common chimpanzee, pygmy chimpanzee and gorilla were sequenced and the lengths and termini of their D-loop DNA's characterized. In these and all other species for which there are data, 5' termini map to sequences that contain the trinucleotide YAY. 3' termini are 25-51...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.13.5841
更新日期:1988-07-11 00:00:00