Evidence map›Paper›PMID 27091962›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Real-time single-molecule electronic DNA sequencing by synthesis using polymer-tagged nucleotides on a nanopore array.

Carl W Fuller, Shiv Kumar, Mintu Porel, Minchen Chien, Arek Bibillo, P Benjamin Stranges, Michael Dorwart, Chuanjuan Tao, Zengmin Li, Wenjing Guo and 22 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
12.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 147 citations in OpenAlex.

  1. Article
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  8. Graphene Nanopore Fabrication and Applications.International journal of molecular sciences · 2025
    Review
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  15. Engineering psychrophilic polymerase for nanopore long-read sequencing.Frontiers in bioengineering and biotechnology · 2024
    Article
  16. Real-time label-free detection of dynamic aptamer-small molecule interactions using a nanopore nucleic acid conformational sensor.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Article
  18. Review
  19. Review
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 4 institutions in 1 country.

Carl W FullerCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027; Genia Technologies, Santa Clara, CA 95050;
Shiv KumarCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Mintu PorelCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Minchen ChienCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Arek BibilloGenia Technologies, Santa Clara, CA 95050;
P Benjamin StrangesDepartment of Genetics, Harvard Medical School, Boston, MA 02115;
Michael DorwartGenia Technologies, Santa Clara, CA 95050;
Chuanjuan TaoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Zengmin LiCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Wenjing GuoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Shundi ShiCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Daniel KorenblumGenia Technologies, Santa Clara, CA 95050;
Andrew TransGenia Technologies, Santa Clara, CA 95050;
Anne AguirreGenia Technologies, Santa Clara, CA 95050;
Edward LiuGenia Technologies, Santa Clara, CA 95050;
Eric T HaradaGenia Technologies, Santa Clara, CA 95050;
James PollardGenia Technologies, Santa Clara, CA 95050;
Ashwini BhatGenia Technologies, Santa Clara, CA 95050;
Cynthia CechGenia Technologies, Santa Clara, CA 95050;
Alexander YangGenia Technologies, Santa Clara, CA 95050;
Cleoma ArnoldGenia Technologies, Santa Clara, CA 95050;
Mirkó PallaDepartment of Genetics, Harvard Medical School, Boston, MA 02115;
Jennifer HovisGenia Technologies, Santa Clara, CA 95050;
Roger ChenGenia Technologies, Santa Clara, CA 95050;
Irina MorozovaCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
Sergey KalachikovCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
James J RussoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027;
John J KasianowiczSemiconductor and Dimension Metrology Division, National Institute of Standards and Technology, Gaithersburg, MD 20899;
Randy DavisGenia Technologies, Santa Clara, CA 95050;
Stefan RoeverGenia Technologies, Santa Clara, CA 95050;
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA 02115; gchurch@genetics.med.harvard.edu dj222@columbia.edu.
Jingyue JuCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027; Department of Chemical Engineering, Columbia University, New York, NY 10027; Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032 gchurch@genetics.med.harvard.edu dj222@columbia.edu.
Columbia University · USNew York Genome Center · USHarvard University · USNational Institute of Standards and Technology · US

Funding

An Integrated System for Single Molecule Electronic Sequencing by SynthesisR01HG007415 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI CHURCH, GEORGE M, JU, JINGYUE · 2013 to 2015
$5.2M
NHGRI NIH HHS R01 HG007415
6 · The paper itself

Abstract

DNA sequencing by synthesis (SBS) offers a robust platform to decipher nucleic acid sequences. Recently, we reported a single-molecule nanopore-based SBS strategy that accurately distinguishes four bases by electronically detecting and differentiating four different polymer tags attached to the 5'-phosphate of the nucleotides during their incorporation into a growing DNA strand catalyzed by DNA polymerase. Further developing this approach, we report here the use of nucleotides tagged at the terminal phosphate with oligonucleotide-based polymers to perform nanopore SBS on an α-hemolysin nanopore array platform. We designed and synthesized several polymer-tagged nucleotides using tags that produce different electrical current blockade levels and verified they are active substrates for DNA polymerase. A highly processive DNA polymerase was conjugated to the nanopore, and the conjugates were complexed with primer/template DNA and inserted into lipid bilayers over individually addressable electrodes of the nanopore chip. When an incoming complementary-tagged nucleotide forms a tight ternary complex with the primer/template and polymerase, the tag enters the pore, and the current blockade level is measured. The levels displayed by the four nucleotides tagged with four different polymers captured in the nanopore in such ternary complexes were clearly distinguishable and sequence-specific, enabling continuous sequence determination during the polymerase reaction. Thus, real-time single-molecule electronic DNA sequencing data with single-base resolution were obtained. The use of these polymer-tagged nucleotides, combined with polymerase tethering to nanopores and multiplexed nanopore sensors, should lead to new high-throughput sequencing methods.

Indexed as

Base SequenceComputer SystemsConductometryDNAEquipment DesignEquipment Failure AnalysisNanoporesNucleotidesOligonucleotide Array Sequence AnalysisPolymersSequence Analysis, DNAStaining and LabelingDNANucleotidesPolymerschip arrayDNA sequencing by synthesisnanoporepolymer-tagged nucleotidessingle-molecule sequencing

Identifiers

PMID27091962
PMCPMC4868432
OpenAlexW2340001130

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.