Abstract：
:Transcriptional regulatory networks specify regulatory proteins controlling the context-specific expression levels of genes. Inference of genome-wide regulatory networks is central to understanding gene regulation, but remains an open challenge. Expression-based network inference is among the most popular methods to infer regulatory networks, however, networks inferred from such methods have low overlap with experimentally derived (e.g. ChIP-chip and transcription factor (TF) knockouts) networks. Currently we have a limited understanding of this discrepancy. To address this gap, we first develop a regulatory network inference algorithm, based on probabilistic graphical models, to integrate expression with auxiliary datasets supporting a regulatory edge. Second, we comprehensively analyze our and other state-of-the-art methods on different expression perturbation datasets. Networks inferred by integrating sequence-specific motifs with expression have substantially greater agreement with experimentally derived networks, while remaining more predictive of expression than motif-based networks. Our analysis suggests natural genetic variation as the most informative perturbation for network inference, and, identifies core TFs whose targets are predictable from expression. Multiple reasons make the identification of targets of other TFs difficult, including network architecture and insufficient variation of TF mRNA level. Finally, we demonstrate the utility of our inference algorithm to infer stress-specific regulatory networks and for regulator prioritization.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Siahpirani AF,Roy Sdoi
10.1093/nar/gkw963subject
Has Abstractpub_date
2017-02-28 00:00:00pages
e21issue
4eissn
0305-1048issn
1362-4962pii
gkw963journal_volume
45pub_type
杂志文章abstract：:Ovarian poly (A) + RNA from Xenopus laevis and Xenopus borealis was used to construct two cDNA libraries which were screened for histone sequences. cDNA clones to H4 mRNA were obtained from both species and an H3 cDNA clone from Xenopus laevis. The complete DNA sequences of these clones have been determined and are pr...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/10.12.3769
更新日期：1982-06-25 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：: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：:Not I linking clones contain sequences flanking Not I recognition sites and were previously shown to be tightly associated with CpG islands and genes. To directly assess the value of Not I clones in genome research, high density grids with 50 000 Not I linking clones originating from six representative Not I linking l...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.7.1635
更新日期：2000-04-01 00:00:00
abstract：:Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. However, GRO-sequencing presents new algorithmic challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not address the uniq...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt1237
更新日期：2014-02-01 00:00:00
abstract：:Topoisomerase II, purified from chicken erythrocytes, was reacted with a large number of different DNA fragments and cleavages were catalogued in the presence and absence of drugs that stabilize the cleavage intermediate. Cleavages were sequenced to derive a consensus for topoisomerase II that predicts catalytic sites...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.12.5533
更新日期：1988-06-24 00:00:00
abstract：:Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5'-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork...
journal_title：Nucleic acids research
pub_type： 杂志文章,评审
doi：10.1093/nar/gkq884
更新日期：2011-02-01 00:00:00
abstract：:MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target inte...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv1258
更新日期：2016-01-04 00:00:00
abstract：:It has been proposed that phage lambda site-specific recombination proceeds via two independent strand exchanges: the first exchange forming a Holliday-structure which is then converted into complete recombinant products by the second strand exchange. If this hypothesis is correct, one should be able to trap the putat...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.14.6839
更新日期：1988-07-25 00:00:00
abstract：:Expression of a proof-reading deficient form of mitochondrial DNA (mtDNA) polymerase gamma, POLG, causes early death accompanied by features of premature ageing in mouse. However, the mechanism of cellular senescence remains unresolved. In addition to high levels of point mutations of mtDNA, the POLG mutator mouse har...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkp091
更新日期：2009-04-01 00:00:00
abstract：:Rfam is a comprehensive collection of non-coding RNA (ncRNA) families, represented by multiple sequence alignments and profile stochastic context-free grammars. Rfam aims to facilitate the identification and classification of new members of known sequence families, and distributes annotation of ncRNAs in over 200 comp...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gki081
更新日期：2005-01-01 00:00:00
abstract：:Abasic sites are common DNA lesions resulting from spontaneous depurination and excision of damaged nucleobases by DNA repair enzymes. However, the influence of the local sequence context on the structure of the abasic site and ultimately, its recognition and repair, remains elusive. In the present study, duplex DNAs ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm622
更新日期：2008-01-01 00:00:00
abstract：:A series of unusual folding regions (UFR) immediately 3' to the cleavage site of the outer membrane protein (OMP) and transmembrane protein (TMP) were detected in the envelope gene RNA of the human immunodeficiency virus (HIV-1, HIV-2) and simian immunodeficiency virus (SIV) by an extensive Monte Carlo simulation. The...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/18.6.1613
更新日期：1990-03-25 00:00:00
abstract：:Isopentenyl adenosine derivatives are always located adjacent to the 3' end of the anticodon in transfer RNA and have been implicated in certain biological functions. In the enteric bacterium, E. coli, the derivative is ms2i6A whereas in some plant associated bacteria the derivative is the hydroxylated form, ms2io6A. ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/10.18.5663
更新日期：1982-09-25 00:00:00
abstract：:Sequential chromatin immunoprecipitation (SeqChIP) is a procedure in which formaldehyde-crosslinked, protein-DNA complexes from living cells are subjected to two sequential immunoprecipitations with antibodies of different specificity. SeqChIP has been used to address, in a qualitative manner, whether two proteins can...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gnh148
更新日期：2004-11-01 00:00:00
abstract：:The DNA data bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) maintains a primary nucleotide sequence database and provides analytical resources for biological information to researchers. This database content is exchanged with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks1152
更新日期：2013-01-01 00:00:00
abstract：:The frequencies of each of the 257 468 complete protein coding sequences (CDSs) have been compiled from the taxonomical divisions of the GenBank DNA sequence database. The sum of the codons used by 8792 organisms has also been calculated. The data files can be obtained from the anonymous ftp sites of DDBJ, Kazusa and ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.1.292
更新日期：2000-01-01 00:00:00
abstract：:A soluble enzyme system that specifically initiates lambda dv plasmid DNA replication at a bacteriophage lambda replication origin [Wold et al. (1982) Proc. Natl. Acad. Sci. USA 79, 6176-6180] is also capable of replicating the single-stranded circular chromosomes of phages M13 and phi X174 to a duplex form. This chai...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/12.7.3069
更新日期：1984-04-11 00:00:00
abstract：:Protein structures are an ensemble of atoms determined experimentally mostly by X-ray crystallography or Nuclear Magnetic Resonance. Studying 3D protein structures is a key point for better understanding protein function at a molecular level. We propose a set of accurate tools, for analysing protein structures, based ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt509
更新日期：2013-07-01 00:00:00
abstract：:Single-nucleotide variation and gene expression of disease samples represent important resources for biomarker discovery. Many databases have been built to host and make available such data to the community, but these databases are frequently limited in scope and/or content. BioMuta, a database of cancer-associated si...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkx907
更新日期：2018-01-04 00:00:00
abstract：:Kaposi's sarcoma-associated herpesvirus encodes four viral homologues to cellular interferon regulatory factors (IRFs), where the most studied is vIRF-1. Even though vIRF-1 shows sequence homology to the N-terminal DNA-binding domain (DBD) of human IRFs, a specific role for this domain in vIRF-1's function has remaine...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt082
更新日期：2013-04-01 00:00:00
abstract：:Alfalfa mosaic virus RNA 4, the subgenomic messenger for viral coat protein, was partially digested with RNase T1 or RNase A and the sequence of a number of fragments was deduced by in vitro labeling with polynucleotide kinase and application of RNA sequencing techniques. From overlapping fragments, the complete prima...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/8.10.2213
更新日期：1980-05-24 00:00:00
abstract：:Stabilization of stalled replication forks prevents excessive fork reversal or degradation, which can undermine genome integrity. The WRN protein is unique among the other human RecQ family members to possess exonuclease activity. However, the biological role of the WRN exonuclease is poorly defined. Recently, the WRN...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkz431
更新日期：2019-07-26 00:00:00
abstract：:The University of Minnesota Biocatalysis/Biodegradation Database (http://www.labmed.umn.edu/umbbd/ ) begins its fifth year having met its initial goals. It contains approximately 100 pathways for microbial catabolic metabolism of primarily xenobiotic organic compounds, including information on approximately 650 reacti...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/28.1.377
更新日期：2000-01-01 00:00:00
abstract：:For the rapid and sensitive detection of p53 'hot spot' mutations, we combined polymerase chain reaction based single-strand conformational polymorphism (PCR-SSCP) analysis with sequence specific-clamping by peptide nucleic acids (PNAs) in a one-step reaction tube protocol. For this purpose, we designed two PNA molecu...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.5.1356
更新日期：1998-03-01 00:00:00
abstract：:RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa. In addition to modifications in non-coding regions, editing contributes to diversification of protein function, in analogy to alternative splicing. However, although splicing programs respond to external signals, fa...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks1045
更新日期：2013-01-01 00:00:00
abstract：:The nucleotide sequence of the celD gene, encoding the previously crystallized endoglucanase D of Clostridium thermocellum, is reported. The enzyme shares a conserved, reiterated domain with the COOH-terminal end of endoglucanases A and B from the same organism. The overexpression in Escherichia coli of celD subcloned...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/14.21.8605
更新日期：1986-11-11 00:00:00
abstract：:The k-junction is a structural motif in RNA comprising a three-way helical junction based upon kink turn (k-turn) architecture. A computer program written to examine relative helical orientation identified the three-way junction of the Arabidopsis TPP riboswitch as an elaborated k-turn. The Escherichia coli TPP ribosw...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku144
更新日期：2014-04-01 00:00:00
abstract：:IMP (Integrative Multi-species Prediction), originally released in 2012, is an interactive web server that enables molecular biologists to interpret experimental results and to generate hypotheses in the context of a large cross-organism compendium of functional predictions and networks. The system provides biologists...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv486
更新日期：2015-07-01 00:00:00
abstract：:The interactions of HIV-1 reverse transcriptase (HIV-1 RT) with a synthetic 53/19-mer DNA substrate was investigated. For this template-primer HIV-1 RT displayed a Km value of 20 nM. The 53/19-mer competitively inhibited DNA synthesis performed on poly (rC).oligo(dG) with Ki value of 260 nM. This corresponded well to ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/21.17.3943
更新日期：1993-08-25 00:00:00
