Abstract:
:Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. We have developed methyl-BEAMing technology to enable absolute quantification of the number of methylated molecules in a sample. Individual DNA fragments are amplified and analyzed either by flow cytometry or next-generation sequencing. We demonstrate enumeration of as few as one methylated molecule in approximately 5,000 unmethylated molecules in DNA from plasma or fecal samples. Using methylated vimentin as a biomarker in plasma samples, methyl-BEAMing detected 59% of cancer cases. In early-stage colorectal cancers, this sensitivity was four times more than that obtained by assaying serum-carcinoembryonic antigen (CEA). With stool samples, methyl-BEAMing detected 41% of cancers and 45% of advanced adenomas. In addition to diagnostic and prognostic applications, this digital quantification of rare methylation events should be applicable to preclinical assessment of new epigenetic biomarkers and quantitative analyses in epigenetic research.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Li M,Chen WD,Papadopoulos N,Goodman SN,Bjerregaard NC,Laurberg S,Levin B,Juhl H,Arber N,Moinova H,Durkee K,Schmidt K,He Y,Diehl F,Velculescu VE,Zhou S,Diaz LA Jr,Kinzler KW,Markowitz SD,Vogelstein Bdoi
10.1038/nbt.1559subject
Has Abstractpub_date
2009-09-01 00:00:00pages
858-63issue
9eissn
1087-0156issn
1546-1696pii
nbt.1559journal_volume
27pub_type
杂志文章abstract::Single-cell RNA sequencing (scRNA-seq) enables the systematic identification of cell populations in a tissue, but characterizing their spatial organization remains challenging. We combine a microarray-based spatial transcriptomics method that reveals spatial patterns of gene expression using an array of spots, each ca...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0392-8
更新日期:2020-03-01 00:00:00
abstract::Paralleling the diversity of genetic and protein activities, pathologic human tissues also exhibit diverse radiographic features. Here we show that dynamic imaging traits in non-invasive computed tomography (CT) systematically correlate with the global gene expression programs of primary human liver cancer. Combinatio...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1306
更新日期:2007-06-01 00:00:00
abstract::The advent of in vitro DNA amplification has enabled rapid acquisition of genomic information. We present here an analogous technique for protein detection, in which the coordinated and proximal binding of a target protein by two DNA aptamers promotes ligation of oligonucleotides linked to each aptamer affinity probe....
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0502-473
更新日期:2002-05-01 00:00:00
abstract::Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centro...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0582-4
更新日期:2020-11-01 00:00:00
abstract::High-density short oligonucleotide microarrays have become a widely used tool for measuring gene expression on a large scale. However, details of the mechanism of binding on microarrays remain unclear. Short oligonucleotide probes currently synthesized on microarrays are often ineffective as a result of limited sequen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt836
更新日期:2003-07-01 00:00:00
abstract::Cellular function is critically regulated through degradation of substrates by the proteasome. To enable direct analysis of naturally cleaved proteasomal peptides under physiological conditions, we developed mass spectrometry analysis of proteolytic peptides (MAPP), a method for proteasomal footprinting that allows fo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4279
更新日期:2018-10-22 00:00:00
abstract::Many promising targets for T-cell-based cancer immunotherapies are self-antigens. During thymic selection, T cells bearing T cell receptors (TCRs) with high affinity for self-antigen are eliminated. The affinity of the remaining low-avidity TCRs can be improved to increase their antitumor efficacy, but conventional sa...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4004
更新日期:2017-12-01 00:00:00
abstract::The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1197-1271
更新日期:1997-11-01 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::Insertional mutagenesis represents a major hurdle to gene therapy and necessitates sensitive preclinical genotoxicity assays. Cdkn2a-/- mice are susceptible to a broad range of cancer-triggering genetic lesions. We exploited hematopoietic stem cells from these tumor-prone mice to assess the oncogenicity of prototypica...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1216
更新日期:2006-06-01 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 gold standard for clinical diagnosis of bacterial lower respiratory infections (LRIs) is culture, which has poor sensitivity and is too slow to guide early, targeted antimicrobial therapy. Metagenomic sequencing could identify LRI pathogens much faster than culture, but methods are needed to remove the large amoun...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0156-5
更新日期:2019-07-01 00:00:00
abstract::Plant satellite RNAs generally reduce the level of helper virus accumulation and attenuate the disease symptoms induced by the helper virus that they depend upon for replication and packaging. As such, satellite RNAs could be used as biocontrol agents to reduce the level of disease in field crops, either by the applic...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1096-1264
更新日期:1996-10-01 00:00:00
abstract::Microbially catalyzed reactions, which occur in the natural sulfur cycle, have been integrated in a microbiological process to remove toxic metals from contaminated soils. Bioleaching using sulfuric acid produced by sulfur-oxidizing bacteria was followed by precipitation of the leachate metals as insoluble sulfides by...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0698-572
更新日期:1998-06-01 00:00:00
abstract::In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell-like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4. In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1335
更新日期:2007-10-01 00:00:00
abstract::Current tools for targeted RNA editing rely on the delivery of exogenous proteins or chemically modified guide RNAs, which may lead to aberrant effector activity, delivery barrier or immunogenicity. Here, we present an approach, called leveraging endogenous ADAR for programmable editing of RNA (LEAPER), that employs s...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0178-z
更新日期:2019-09-01 00:00:00
abstract::Embryonic stem (ES) cells are a promising source of cardiomyocytes, but clinical application of ES cells has been hindered by the lack of reliable selective differentiation methods. Differentiation into any lineage is partly dependent on the regulatory mechanisms of normal early development. Although several signals, ...
journal_title:Nature biotechnology
pub_type: 信件
doi:10.1038/nbt1093
更新日期:2005-05-01 00:00:00
abstract::New cultivars with very erect leaves, which increase light capture for photosynthesis and nitrogen storage for grain filling, may have increased grain yields. Here we show that the erect leaf phenotype of a rice brassinosteroid-deficient mutant, osdwarf4-1, is associated with enhanced grain yields under conditions of ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1173
更新日期:2006-01-01 00:00:00
abstract::Field tests of corn co-expressing two new delta-endotoxins from Bacillus thuringiensis (Bt) have demonstrated protection from root damage by western corn rootworm (Diabrotica virgifera virgifera LeConte). The level of protection exceeds that provided by chemical insecticides. In the bacterium, these proteins form crys...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/90282
更新日期:2001-07-01 00:00:00
abstract::Excessive and prolonged activity of inflammatory monocytes is a hallmark of many diseases with an inflammatory component. In such conditions, precise targeting of these cells could be therapeutically beneficial while sparing many essential functions of the innate immune system, thus limiting unwanted effects. Inflamma...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1989
更新日期:2011-10-09 00:00:00
abstract::We have evaluated inhibition of the plasmid-born chloramphenicol acetyl transferase gene (CAT) by the hammerhead ribozyme and antisense RNA in Escherichia coli where the translation and transcription rates have been modified. Whereas neither antisense nor the hammerhead had an inhibitory effect on CAT activity in wild...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0597-432
更新日期:1997-05-01 00:00:00
abstract::A variety of strategies to incorporate unnatural amino acids into proteins have been pursued, but all have limitations with respect to technical accessibility, scalability, applicability to in vivo studies, or site specificity of amino acid incorporation. The ability to selectively introduce unnatural functional group...
journal_title:Nature biotechnology
pub_type:
doi:10.1038/nbt742
更新日期:2002-10-01 00:00:00
abstract::The targeting scope of Streptococcus pyogenes Cas9 (SpCas9) and its engineered variants is largely restricted to protospacer-adjacent motif (PAM) sequences containing G bases. Here we report the evolution of three new SpCas9 variants that collectively recognize NRNH PAMs (where R is A or G and H is A, C or T) using ph...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0412-8
更新日期:2020-04-01 00:00:00
abstract::Increasing the in vivo residence times of protein therapeutics could decrease their dosing frequencies. We show that genetic fusion of an unstructured recombinant polypeptide of 864 amino acids, called XTEN, to a peptide or protein provides an apparently generic approach to extend plasma half-life. Allometric scaling ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1588
更新日期:2009-12-01 00:00:00
abstract::Dual-color fluorescence cross-correlation spectroscopy (FCCS) is a promising technique for quantifying protein-protein interactions. In this technique, two different fluorescent labels are excited and detected simultaneously within a common measurement volume. Difficulties in aligning two laser lines and emission cros...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1207
更新日期:2006-05-01 00:00:00
abstract::Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets. We report a method to specifically capture an arbitrary subset of genomic targets for single-molecule bisulfite sequencing for digital quantification of DNA methylation at single-nucleotide...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1530
更新日期:2009-04-01 00:00:00
abstract::Can new approaches for deriving human stem cells circumnavigate existing patents that dominate embryonic stem cell intellectual property? ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0406-411
更新日期:2006-04-01 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
abstract::To select for bacterial strains with enhanced phenotypes, random fragments of a whole genome, or a defined region of the genome, are cloned in a nonreplicating vector. The resulting plasmids are integrated by recombination into the homologous DNA region of the original strain. Integration gives rise to a nontandem dir...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0697-564
更新日期:1997-06-01 00:00:00
abstract::We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing mic...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/76469
更新日期:2000-06-01 00:00:00