Abstract：
:Advances in single-cell RNA-sequencing techniques reveal the existence of distinct cell subpopulations. Identification of transcription factors (TFs) that define the identity of these subpopulations poses a challenge. Here, we postulate that identity depends on background subpopulations, and is determined by a synergistic core combination of TFs mainly uniquely expressed in each subpopulation, but also TFs more broadly expressed across background subpopulations. Building on this view, we develop a new computational method for determining such synergistic identity cores of subpopulations within a given cell population. Our method utilizes an information-theoretic measure for quantifying transcriptional synergy, and implements a novel algorithm for searching for optimal synergistic cores. It requires only single-cell RNA-seq data as input, and does not rely on any prior knowledge of candidate genes or gene regulatory networks. Hence, it can be directly applied to any cellular systems, including those containing novel subpopulations. The method is capable of recapitulating known experimentally validated identity TFs in eight published single-cell RNA-seq datasets. Furthermore, some of these identity TFs are known to trigger cell conversions between subpopulations. Thus, this methodology can help design strategies for cell conversion within a cell population, guiding experimentalists in the field of stem cell research and regenerative medicine.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Okawa S,Del Sol Adoi
10.1093/nar/gkz147subject
Has Abstractpub_date
2019-04-23 00:00:00pages
3333-3343issue
7eissn
0305-1048issn
1362-4962pii
5366475journal_volume
47pub_type
杂志文章abstract：:A method is described which allows selection of sequences which can substitute for the normal AATAAA hexanucleotide involved in polyadenylation of SV40 late mRNAs. Plaques were generated from viral DNA lacking the motif, forcing acquisition of substitute sequences. Four variants were characterized. All displayed wild-...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/13.22.8053
更新日期：1985-11-25 00:00:00
abstract：:The far upstream region of herpes simplex virus (HSV) immediate early (IE) gene 3 has previously been shown to increase gene expression in an enhancer-like manner, and to contain sequences which respond to stimulation of transcription by a virion polypeptide, Vmw65. To analyse the specific DNA sequences which mediate ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/14.2.929
更新日期：1986-01-24 00:00:00
abstract：:Previous studies have shown that the yeast Candida albicans encodes a unique seryl-tRNA(CAG) that should decode the leucine codon CUG as serine. However, in vitro translation of several different CUG-containing mRNAs in the presence of this unusual seryl-tRNA(CAG) result in an apparent increase in the molecular weight...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/23.9.1481
更新日期：1995-05-11 00:00:00
abstract：:We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkf566
更新日期：2002-10-15 00:00:00
abstract：:In this paper we focus on the detection of differentially expressed genes according to changes in hybridization signals using statistical tests. These tests were applied to 14 208 zebrafish cDNA clones that were immobilized on a nylon support and hybridized with radioactively labeled target mRNA from wild-type and lit...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/29.23.e117
更新日期：2001-12-01 00:00:00
abstract：:Cloned ribosomal DNA (rDNA) of Locusta migratoria was analyzed by restriction site mapping and SI nuclease experiments. The repeat unit is 18 kb long. The nontranscribed spacer region (NTS) is very large (11 kb) and homogeneous in length, but many of the restriction sites are heterogeneous among the repeat units. Two ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/13.4.1251
更新日期：1985-02-25 00:00:00
abstract：:Histone H2A ubiquitination plays critical roles in transcriptional repression and deoxyribonucleic acid (DNA) damage response. More attention has been focused on ubiquitin E3 ligases of H2A, however, less is known about the negative regulators of H2A ubiquitination. Here we identified HSCARG as a new negative regulato...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku230
更新日期：2014-05-01 00:00:00
abstract：:We have developed an improved method for photofootprinting in vivo which utilizes the thermostable DNA polymerase from T. aquaticus (Taq) in a primer extension assay. UV light is used to introduce photoproducts into the genomic DNA of intact yeast cells. The photoproducts are then detected and mapped at the nucleotide...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/17.1.171
更新日期：1989-01-11 00:00:00
abstract：:R spider is a web-based tool for the analysis of a gene list using the systematic knowledge of core pathways and reactions in human biology accumulated in the Reactome and KEGG databases. R spider implements a network-based statistical framework, which provides a global understanding of gene relations in the supplied ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkq482
更新日期：2010-07-01 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：:DNA lengths in the structural repeat units of Chinese hamster ovary (CHO) and chicken erythrocyte chromatin were compared by analyzing the sizes of DNA fragments produced after treatment of nuclei with staphylococcal nuclease. The repeat length of CHO chromatin (173 +- 4 BP) is about 20 base pairs (BP) smaller than th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/4.4.771
更新日期：1977-04-01 00:00:00
abstract：:The 3' splice site of the second intron (I2) of the human apolipoprotein-AII gene, (GT)16GGGCAG, is unique in that, although fully functional, a stretch of alternating guanine and thymine residues replaces the polypyrimidine tract usually associated with 3' splice junctions. The transient expression of successive 5' d...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/15.9.3787
更新日期：1987-05-11 00:00:00
abstract：:Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly infl...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gky687
更新日期：2018-11-02 00:00:00
abstract：:Unlike short interfering RNAs (siRNAs), which are commonly designed to repress a single messenger RNA (mRNA) target through perfect base pairing, microRNAs (miRNAs) are endogenous small RNAs that have evolved to concurrently repress multiple mRNA targets through imperfect complementarity. MicroRNA target recognition i...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku171
更新日期：2014-05-01 00:00:00
abstract：:Histone proteins are synthesized in large amounts during S-phase to package the newly replicated DNA, and are among the most stable proteins in the cell. The replication-dependent (RD)-histone mRNAs expressed during S-phase end in a conserved stem-loop rather than a polyA tail. In addition, there are replication-indep...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw620
更新日期：2016-11-02 00:00:00
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 ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr407
更新日期：2011-09-01 00:00:00
abstract：:Guanine-rich sequences are highly abundant in the human genome, especially in regulatory regions. Because guanine-rich sequences have the unique ability to form G-quadruplexes, these structures may play a role in the regulation of gene transcription. In previous studies, we demonstrated that formation of G-quadruplexe...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkr259
更新日期：2011-09-01 00:00:00
abstract：:A number of different protecting groups were compared with respect to their usefulness for protection of 2'-hydroxyl functions during synthesis of oligoribonucleotides using the H-phosphonate approach. The comparison was between the t-butyldimethylsilyl (t-BDMSi), the o-chlorobenzoyl (o-CIBz), the tetrahydropyranyl (T...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.1.94
更新日期：1994-01-11 00:00:00
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journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/27.15.3057
更新日期：1999-08-01 00:00:00
abstract：:The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding. NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction (PPI) netwo...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkz240
更新日期：2019-07-02 00:00:00
abstract：:UMSBP is a CCHC-type zinc finger protein, which functions during replication initiation of kinetoplast DNA minicircles and the segregation of kinetoplast DNA networks. Interactions of UMSBP with origin sequences, as well as the protein oligomerization, are affected by its redox state. Reduction yields UMSBP monomers a...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkn927
更新日期：2009-01-01 00:00:00
abstract：:When the function of origins of replication in yeast was compromised by placing ARS sequences downstream of strong promoters, ARS activity might have been affected either by transcription or by an altered chromatin configuration induced by the construct. To distinguish between these possibilities, derivatives of the y...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/22.19.3904
更新日期：1994-09-25 00:00:00
abstract：:Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell M...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gky152
更新日期：2018-05-18 00:00:00
abstract：:Highly repetitive Hind III restriction fragments of 0.72-0.76 KBP from total Xenopus laevis genomic DNA are organized in a tandem like arrangement. Cloning of these fragments in pBR 322 with subsequent restriction site mapping and nucleotide sequence analysis of some selected clones showed two different types of seque...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/11.20.6997
更新日期：1983-10-25 00:00:00
abstract：:Correlation of motif occurrences with gene expression intensity is an effective strategy for elucidating transcriptional cis-regulatory logic. Here we demonstrate that this approach can also identify cis-regulatory elements for alternative pre-mRNA splicing. Using data from a human exon microarray, we identified 56 ca...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm485
更新日期：2007-01-01 00:00:00
abstract：:Few transcriptional regulatory networks have been described in non-model organisms. In Entamoeba histolytica seminal aspects of pathogenesis are transcriptionally controlled, however, little is known about transcriptional regulatory networks that effect gene expression in this parasite. We used expression data from tw...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm028
更新日期：2007-01-01 00:00:00
abstract：:Many microRNAs (miRNAs) are co-regulated during the same physiological process but the underlying cellular logic is often little understood. The conserved, immunomodulatory miRNAs miR-146 and miR-155, for instance, are co-induced in many cell types in response to microbial lipopolysaccharide (LPS) to feedback-repress ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks1030
更新日期：2013-01-07 00:00:00
abstract：:The aminoacylation kinetics of T7 transcripts representing defined regions of Escherichia coli serine tRNAs were determined using purified E.coli seryl-tRNA synthetase (SerRS) and the kinetic values were used to estimate the relative contribution of various tRNA(Ser) domains to recognition by SerRS. The analysis revea...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/21.19.4467
更新日期：1993-09-25 00:00:00
abstract：:Protein-RNA interactions in small nuclear ribonucleoproteins (UsnRNPs) from HeLa cells were investigated by irradiation of purified nucleoplasmic snRNPs U1 to U6 with UV light at 254 nm. The cross-linked proteins were analyzed on one- and two-dimensional gel electrophoresis systems, and the existence of a stable cross...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/16.23.10985
更新日期：1988-12-09 00:00:00
abstract：:A simple method, primer specific and mispair extension analysis (PSMEA) with pfu DNA polymerase was developed for genotyping. PSMEA is based on the unique properties of 3'-->5' exonuclease proofreading activity. In the presence of an incomplete set of dNTPs, pfu was found to be extremely discriminative in nucleotide i...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/26.21.5013
更新日期：1998-11-01 00:00:00
