Abstract：
:The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes are governed by the repertoire of expressed genes, and the levels and timing of expression, it is important to have experimental tools for the direct monitoring of large numbers of mRNAs in parallel. We have developed an approach that is based on hybridization to small, high-density arrays containing tens of thousands of synthetic oligonucleotides. The arrays are designed based on sequence information alone and are synthesized in situ using a combination of photolithography and oligonucleotide chemistry. RNAs present at a frequency of 1:300,000 are unambiguously detected, and detection is quantitative over more than three orders of magnitude. This approach provides a way to use directly the growing body of sequence information for highly parallel experimental investigations. Because of the combinatorial nature of the chemistry and the ability to synthesize small arrays containing hundreds of thousands of specifically chosen oligonucleotides, the method is readily scalable to the simultaneous monitoring of tens of thousands of genes.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Lockhart DJ,Dong H,Byrne MC,Follettie MT,Gallo MV,Chee MS,Mittmann M,Wang C,Kobayashi M,Horton H,Brown ELdoi
10.1038/nbt1296-1675subject
Has Abstractpub_date
1996-12-01 00:00:00pages
1675-80issue
13eissn
1087-0156issn
1546-1696journal_volume
14pub_type
杂志文章abstract：:The scale and capabilities of single-cell RNA-sequencing methods have expanded rapidly in recent years, enabling major discoveries and large-scale cell mapping efforts. However, these methods have not been systematically and comprehensively benchmarked. Here, we directly compare seven methods for single-cell and/or si...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-020-0465-8
更新日期：2020-06-01 00:00:00
abstract：:Organophosphorus hydrolase (OPH) was displayed and anchored onto the surface of Escherichia coli using an Lpp-OmpA fusion system. Production of the fusion proteins in membrane fractions was verified by immunoblotting with OmpA antisera. Inclusion of the organophosphorus hydrolase signal sequence was necessary for achi...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1097-984
更新日期：1997-10-01 00:00:00
abstract：:Forster Resonance Energy Transfer has served as a molecular ruler that reports conformational changes and intramolecular distances of single biomolecules. However, such rulers suffer from low and fluctuating signal intensities, limited observation time due to photobleaching, and an upper distance limit of approximatel...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1100
更新日期：2005-06-01 00:00:00
abstract：:Isolating antigen-specific T lymphocytes is hampered by the low frequency of the cells and the low affinity between T-cell receptors (TCR) and antigen. We describe the isolation and purification of antigen-specific CD8+ T lymphocytes from mixed T-cell populations. Magnetic beads coated with major histocompatibility co...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0398-281
更新日期：1998-03-01 00:00:00
abstract：:We have identified a heptapeptide with high affinity to rheumatoid arthritis-associated class II major histocompatibility (MHC) molecules. Using a model of its interaction with the class II binding site, a variety of mimetic substitutions were introduced into the peptide. Several unnatural amino acids and dipeptide mi...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/9865
更新日期：1999-06-01 00:00:00
abstract：:The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-019-0197-9
更新日期：2019-08-01 00:00:00
abstract：:Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Although such analyses typically assume that a protein's peptide fragments are observed with equal likelihood, only a few so-called 'proteotypic' peptides are repeatedly and consistently identified fo...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1275
更新日期：2007-01-01 00:00:00
abstract：:After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt.3765
更新日期：2017-03-01 00:00:00
abstract：:Can weakly active phytochemicals be combined synergistically to produce new antibacterial treatments? ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1206-1504
更新日期：2006-12-01 00:00:00
abstract：:Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenge...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt.3365
更新日期：2015-10-01 00:00:00
abstract：:Little is known about the consequences of releasing genetically engineered plants (GEP) into the environment. Using opine-producing GEP, we show that transgenic plants alter their biological environment, more precisely the root-associated bacterial populations. The alterations were both transgene-specific and target p...
journal_title：Nature biotechnology
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doi：10.1038/nbt0497-369
更新日期：1997-04-01 00:00:00
abstract：:Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AA...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3440
更新日期：2016-02-01 00:00:00
abstract：:Antifreeze proteins (AFPs) are found in cold-adapted organisms and have the unusual ability to bind to and inhibit the growth of ice crystals. However, the underlying molecular basis of their ice-binding activity is unclear because of the difficulty of studying the AFP-ice interaction directly and the lack of a common...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1224
更新日期：2006-07-01 00:00:00
abstract：:We constructed an immunotoxin, composed of an antibody directed against the high-affinity IgG receptor CD64 and Ricin-A, with the aim of resolving chronic inflammation through elimination of activated macrophages. In vitro, this immunotoxin proved very efficient in inducing apoptosis in activated macrophages, leaving ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/71908
更新日期：2000-01-01 00:00:00
abstract：:We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2052
更新日期：2011-11-27 00:00:00
abstract：:The human transcriptome is marked by extensive alternative mRNA splicing and the expression of many closely related genes, which may be difficult to distinguish using standard microarray techniques. Here we describe a sensitive and specific assay for parallel analysis of mRNA isoforms on a fiber-optic microarray platf...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0402-353
更新日期：2002-04-01 00:00:00
abstract：:As the cost of human genome sequencing plunges and large-scale genome-phenotype studies become possible, society should do more to reward those individuals who choose to disclose their data, despite the risks. ...
journal_title：Nature biotechnology
pub_type： 评论,社论
doi：10.1038/nbt0909-777
更新日期：2009-09-01 00:00:00
abstract：:RNA-guided genome editing with the CRISPR-Cas9 system has great potential for basic and clinical research, but the determinants of targeting specificity and the extent of off-target cleavage remain insufficiently understood. Using chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we mapped genom...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2916
更新日期：2014-07-01 00:00:00
abstract：:The basics of determining valuation will help you to understand what criteria matter most for investors. ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：
更新日期：2004-08-01 00:00:00
abstract：:We report the use of an atomic force microscopy (AFM)-based force spectroscopy technique to identify, at the single-molecule level, the components of mixtures of polysaccharides. Previously, we showed that the elasticity of certain types of polysaccharides is governed by force-induced conformational transitions of the...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/85712
更新日期：2001-03-01 00:00:00
abstract：:We describe a novel approach to design a set of primers selective for large groups of genes. This method is based on the distribution frequency of all nucleotide combinations (octa- to decanucleotides), and the combined ability of primer pairs, based on these oligonucleotides, to detect genes. By analyzing 1000 human ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0796-857
更新日期：1996-07-01 00:00:00
abstract：:The side chain of the antifungal antibiotic ansatrienin A from Streptomyces collinus contains a cyclohexanecarboxylic acid (CHC)-derived moiety. This moiety is also observed in trace amounts of omega-cyclohexyl fatty acids (typically less than 1% of total fatty acids) produced by S. collinus. Coenzyme A-activated CHC ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/79479
更新日期：2000-09-01 00:00:00
abstract：:Although mass spectrometry has become a powerful tool for the functional analysis of biological systems, complete proteome characterization cannot yet be achieved. Instead, the sheer complexity of living organisms demands fractionation of cellular extracts to enable more targeted analyses. Here, we introduce the conce...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1076
更新日期：2005-04-01 00:00:00
abstract：:Tyrosine phosphorylation exerts a pivotal role in cell regulation processes of higher eukaryotes. Tight control of the activity of protein tyrosine kinases is crucial for ordered phosphorylation to occur. We have developed a functional screen for tyrosine kinase regulators using c-Src, the first cellular protein tyros...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0596-600
更新日期：1996-05-01 00:00:00
abstract：:The interaction between the HSP90 chaperone and its client kinases is sensitive to the conformational status of the kinase, and stabilization of the kinase fold by small molecules strongly decreases chaperone interaction. Here we exploit this observation and assay small-molecule binding to kinases in living cells, usi...
journal_title：Nature biotechnology
pub_type： 杂志文章
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更新日期：2013-07-01 00:00:00
abstract：:We have developed a strategy for improving the stimulation of T cells during immune responses by constructing recombinant antibodies that enhance the delivery of antigen to antigen-presenting cells, such as B cells. These antibodies have variable regions specific for surface molecules on B cells, and a constant region...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/10883
更新日期：1999-07-01 00:00:00
abstract：:Circular RNA transcripts were first identified in the early 1990s but knowledge of these species has remained limited, as their study through traditional methods of RNA analysis has been difficult. Now, novel bioinformatic approaches coupled with biochemical enrichment strategies and deep sequencing have allowed compr...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2890
更新日期：2014-05-01 00:00:00
abstract：:Colorectal cancer (CRC) is a leading cause of death in the developed world, yet facile preclinical models that mimic the natural stages of CRC progression are lacking. Through the orthotopic engraftment of colon organoids we describe a broadly usable immunocompetent CRC model that recapitulates the entire adenoma-aden...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3837
更新日期：2017-06-01 00:00:00
abstract：:A major shortcoming to the use of adeno-associated virus (rAAV) vectors is their limited packaging size. To overcome this hurdle, we split an expression cassette and cloned it into two separate vectors. The vectors contained either a nuclear localizing Escherichia coli lacZ transgene (nlslacZ) with a splice acceptor, ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/75390
更新日期：2000-05-01 00:00:00
abstract：:The nonprofit Pew Initiative on Food and Biotechnology is closing, but the need for an independent and neutral body to facilitate dialog on US biotech policy has never been greater. ...
journal_title：Nature biotechnology
pub_type： 社论
doi：10.1038/nbt0207-143
更新日期：2007-02-01 00:00:00
