Abstract：
:Data produced with short-read sequencing technologies result in ambiguous haplotyping and a limited capacity to investigate the full repertoire of biologically relevant forms of genetic variation. The notion of haplotype-resolved sequencing data has recently gained traction to reduce this unwanted ambiguity and enable exploration of other forms of genetic variation; beyond studies of just nucleotide polymorphisms, such as compound heterozygosity and structural variations. Here we describe Droplet Barcode Sequencing, a novel approach for creating linked-read sequencing libraries by uniquely barcoding the information within single DNA molecules in emulsion droplets, without the aid of specialty reagents or microfluidic devices. Barcode generation and template amplification is performed simultaneously in a single enzymatic reaction, greatly simplifying the workflow and minimizing assay costs compared to alternative approaches. The method has been applied to phase multiple loci targeting all exons of the highly variable Human Leukocyte Antigen A (HLA-A) gene, with DNA from eight individuals present in the same assay. Barcode-based clustering of sequencing reads confirmed analysis of over 2000 independently assayed template molecules, with an average of 753 reads in support of called polymorphisms. Our results show unequivocal characterization of all alleles present, validated by correspondence against confirmed HLA database entries and haplotyping results from previous studies.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Redin D,Borgström E,He M,Aghelpasand H,Käller M,Ahmadian Adoi
10.1093/nar/gkx436subject
Has Abstractpub_date
2017-07-27 00:00:00pages
e125issue
13eissn
0305-1048issn
1362-4962pii
3835310journal_volume
45pub_type
杂志文章abstract：:In neural stem cells (NSCs), the balance between stem cell maintenance and neuronal differentiation depends on cell-fate determinants such as TRIM32. Previously, we have shown that TRIM32 associates with the RNA-induced silencing complex and increases the activity of microRNAs such as Let-7a. However, the exact mechan...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv138
更新日期：2015-03-11 00:00:00
abstract：:We have isolated a unique fragment of the HLA-DR alpha gene and probed human genomic DNA at low stringency to search for homologous sequences. A minimum of six non-polymorphic cross-hybridizing high molecular weight fragments were found in all DNAs examined. In order to obtain molecular clones of these cross-hybridizi...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/13.20.7515
更新日期：1985-10-25 00:00:00
abstract：:Phage_Finder, a heuristic computer program, was created to identify prophage regions in completed bacterial genomes. Using a test dataset of 42 bacterial genomes whose prophages have been manually identified, Phage_Finder found 91% of the regions, resulting in 7% false positive and 9% false negative prophages. A searc...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl732
更新日期：2006-01-01 00:00:00
abstract：:G-quadruplexes play various roles in multiple biological processes, which can be positive when a G4 is involved in the regulation of gene expression or detrimental when the folding of a stable G4 impairs DNA replication promoting genome instability. This duality interrogates the significance of their presence within g...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkz463
更新日期：2019-07-09 00:00:00
abstract：:The accurate structural modeling of B- and T-cell receptors is fundamental to gain a detailed insight in the mechanisms underlying immunity and in developing new drugs and therapies. The LYRA (LYmphocyte Receptor Automated modeling) web server (http://www.cbs.dtu.dk/services/LYRA/) implements a complete and automated ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkv535
更新日期：2015-07-01 00:00:00
abstract：:Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and mo...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gks1111
更新日期：2013-01-01 00:00:00
abstract：:ModBase (http://salilab.org/modbase) is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on Modeller for fold assignment, sequence-structure alignment, model building and model assessment (http://salilab.org/modelle...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt1144
更新日期：2014-01-01 00:00:00
abstract：:The molecular organization of the dunce gene of Drosophila melanogaster has proved to be particularly complex, with two divergently transcribed genes, Sgs-4 and Pig-1, nested within its 79 kb intron (1). Here we report the identification and the molecular characterization of a third gene nested within the transcriptio...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/18.19.5837
更新日期：1990-10-11 00:00:00
abstract：:A set of new sulfurizing agents representing disulfides of arylsulfonic acids has been developed for the automated synthesis of phosphorothioate oligonucleotide analogues via the phosphoramidite method. These reagents, such as bis(benzenesulfonyl)disulfide, bis(p-toluenesulfonyl)disulfide, bis(p-methoxybenzensulfonyl)...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/23.20.4029
更新日期：1995-10-25 00:00:00
abstract：:Lateral ribosomal stalk is responsible for binding and recruiting translation factors during protein synthesis. The eukaryotic stalk consists of one P0 protein with two copies of P1•P2 heterodimers to form a P0(P1•P2)₂ pentameric P-complex. Here, we have solved the structure of full-length P1•P2 by nuclear magnetic re...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt636
更新日期：2013-10-01 00:00:00
abstract：:Defining syntenic relationships among orthologous gene clusters is a frequent undertaking of biologists studying organismal evolution through comparative genomic approaches. With the increasing availability of genome data made possible through next-generation sequencing technology, there is a growing need for user-fri...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkw330
更新日期：2016-07-08 00:00:00
abstract：:Acetyl-CoA Carboxylase catalyzes the first committed step in fatty acid synthesis. Escherichia coli acetyl-CoA carboxylase is composed of biotin carboxylase, carboxyltransferase and biotin carboxyl carrier protein functions. The accA and accD genes that code for the alpha- and beta-subunits, respectively, are not in a...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkp1079
更新日期：2010-03-01 00:00:00
abstract：:The effect of temperature and primer concentration on oligonucleotide-primed transcription has been studied using the separated strands of a well-defined natural DNA as template. Results were similar to those obtained in the homopolymer-directed model systems. At high temperature and excess primer concentration mainly...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/4.2.445
更新日期：1977-02-01 00:00:00
abstract：:The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. Th...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkm753
更新日期：2007-01-01 00:00:00
abstract：:Computational modelling of mammalian cell cycle regulation is a challenging task, which requires comprehensive knowledge on many interrelated processes in the cell. We have developed a web-based integrated database on cell cycle regulation in mammals in normal and pathological states (Cyclonet database). It integrates...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkl912
更新日期：2007-01-01 00:00:00
abstract：:The covalent attachment of thiol-modified DNA oligomers; to self-assembled monolayer silane films on fused silica and oxidized silicon substrates is described. A heterobifunctional crosslinking molecule bearing both thiol- and amino-reactive moieties was used to tether a DNA oligomer (modified at its terminus with a t...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/24.15.3031
更新日期：1996-08-01 00:00:00
abstract：:The disappearance of defined restriction fragments of the beta 1-globin, an albumin and the A1 vitellogenin gene was quantitated after DNase I digestion and expressed by a sensitivity factor defined by a mathematical model. Analysis of naked DNA showed that the gene fragments have similar but not identical sensitivity...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/9.11.2455
更新日期：1981-06-11 00:00:00
abstract：:The process of strand exchange is considered to be the hallmark of DNA recombination. Proteins known to carry out such exchange are believed to operate via one or the other of two mechanisms. RecA-like proteins promote the formation of a three-stranded or triplex synaptic intermediate in which strand exchange occurs, ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/25.20.4004
更新日期：1997-10-15 00:00:00
abstract：:We show that using low denaturation temperatures (80-88 degrees C) during ligation mediated PCR (LM PCR) of bacterial DNA leads to the amplification of limited sets of the less stable DNA fragments. A set of electrophoretic patterns of such fragments obtained at different denaturation temperatures forms the PCR meltin...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gng116
更新日期：2003-09-15 00:00:00
abstract：:Hepatitis C virus (HCV) RNA is recognized and cleaved in vitro by RNase P enzyme near the AUG start codon. Because RNase P identifies transfer RNA (tRNA) precursors, it has been proposed that HCV RNA adopts structural similarities to tRNA. Here, we present experimental evidence of RNase P sensitivity conservation in n...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gki290
更新日期：2005-03-08 00:00:00
abstract：:The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkn112
更新日期：2008-05-01 00:00:00
abstract：:A fluoride-cleavable phosphoramidite for biotinylation was designed, synthesized and coupled efficiently to the 5'-end of DNA on an automatic synthesizer. The diisopropylsilyl acetal functionality was used to link the biotin moiety through a tertiary hydroxide group to the 5'-end of DNA. This linkage proved to be comp...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkg130
更新日期：2003-01-15 00:00:00
abstract：:Metagenomics is a relatively recently established but rapidly expanding field that uses high-throughput next-generation sequencing technologies to characterize the microbial communities inhabiting different ecosystems (including oceans, lakes, soil, tundra, plants and body sites). Metagenomics brings with it a number ...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt961
更新日期：2014-01-01 00:00:00
abstract：:In kinetoplastid protozoa, mitochondrial (mt) mRNAs are post-transcriptionally edited by insertion and deletion of uridylate residues, the information being provided by guide (g)RNAs. Currently popular mechanisms for the editing process envisage a series of consecutive 'cut-and-paste' reactions, carried out by a compl...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/29.14.2950
更新日期：2001-07-15 00:00:00
abstract：:Post-translational modifications (PTMs) play a key role in numerous cellular processes by directly affecting structure, dynamics and interaction networks of target proteins. Despite their importance, our understanding of protein PTMs at the atomistic level is still largely incomplete. Molecular dynamics (MD) simulatio...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt416
更新日期：2013-07-01 00:00:00
abstract：:The database of molecular motions, MolMovDB (http://molmovdb.org), has been in existence for the past decade. It classifies macromolecular motions and provides tools to interpolate between two conformations (the Morph Server) and predict possible motions in a single structure. In 2005, we expanded the services offered...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkj046
更新日期：2006-01-01 00:00:00
abstract：:X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 368 entries from 318 unrelated families showing 228 unique molecular events. In addi...
journal_title：Nucleic acids research
pub_type： 杂志文章,多中心研究
doi：10.1093/nar/25.1.166
更新日期：1997-01-01 00:00:00
abstract：:Approximately half of all human transcripts contain at least one upstream translational initiation site that precedes the main coding sequence (CDS) and gives rise to an upstream open reading frame (uORF). We generated uORFdb, publicly available at http://cbdm.mdc-berlin.de/tools/uorfdb, to serve as a comprehensive li...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt952
更新日期：2014-01-01 00:00:00
abstract：:Developmental stage-specific expression of the β-type globin genes is regulated by many cis- and trans-acting components. The adult β-globin gene contains an E-box located 60 bp downstream of the transcription start site that has been shown to bind transcription factor upstream stimulatory factor (USF) and to contribu...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gku107
更新日期：2014-04-01 00:00:00
abstract：:Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the earl...
journal_title：Nucleic acids research
pub_type： 杂志文章
doi：10.1093/nar/gkt1293
更新日期：2014-03-01 00:00:00
