Evidence map›Paper›PMID 23093720›Full record

ArticleGenome research2013

Modeling kinetic rate variation in third generation DNA sequencing data to detect putative modifications to DNA bases.

Eric E Schadt, Onureena Banerjee, Gang Fang, Zhixing Feng, Wing H Wong, Xuegong Zhang, Andrey Kislyuk, Tyson A Clark, Khai Luong, Alona Keren-Paz and 6 more

Abstract read
In one paragraph

Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
–field-weighted citation impact
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

65 citing papers in PubMed.

  1. Review
  2. Replication-coupled hemimethylation inFrontiers in microbiology · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Sequencing of NMolecular cell · 2024
    Article
  10. Long-read sequencing for brain tumors.Frontiers in oncology · 2024
    Review
  11. Article
  12. Comparison ofEpigenomes · 2023
    Article
  13. Shaping eukaryotic epigenetic systems by horizontal gene transfer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Eric E SchadtDepartment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA. eric.schadt@mssm.edu
Onureena Banerjee
Gang Fang
Zhixing Feng
Wing H Wong
Xuegong Zhang
Andrey Kislyuk
Tyson A Clark
Khai Luong
Alona Keren-Paz
Andrew Chess
Vipin Kumar
Alice Chen-Plotkin
Neal Sondheimer
Jonas Korlach
Andrew Kasarskis

Funding

Direct Single Base-Pair Real-Time DNA Methylation SequencingRC2HG005618 · NHGRI · PACIFIC BIOSCIENCES OF CALIFORNIA, INC. · PI TURNER, STEPHEN WHITFIELD · 2009 to 2010
$1.2M
Mitochondrial Transcription and Pediatric DiseaseK08HD058022 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI SONDHEIMER, NEAL J · 2009 to 2013
$670k
NHGRI NIH HHS 1RC2HG005618-01NHGRI NIH HHS RC2 HG005618NICHD NIH HHS K08 HD058022
6 · The paper itself

Abstract

Current generation DNA sequencing instruments are moving closer to seamlessly sequencing genomes of entire populations as a routine part of scientific investigation. However, while significant inroads have been made identifying small nucleotide variation and structural variations in DNA that impact phenotypes of interest, progress has not been as dramatic regarding epigenetic changes and base-level damage to DNA, largely due to technological limitations in assaying all known and unknown types of modifications at genome scale. Recently, single-molecule real time (SMRT) sequencing has been reported to identify kinetic variation (KV) events that have been demonstrated to reflect epigenetic changes of every known type, providing a path forward for detecting base modifications as a routine part of sequencing. However, to date no statistical framework has been proposed to enhance the power to detect these events while also controlling for false-positive events. By modeling enzyme kinetics in the neighborhood of an arbitrary location in a genomic region of interest as a conditional random field, we provide a statistical framework for incorporating kinetic information at a test position of interest as well as at neighboring sites that help enhance the power to detect KV events. The performance of this and related models is explored, with the best-performing model applied to plasmid DNA isolated from Escherichia coli and mitochondrial DNA isolated from human brain tissue. We highlight widespread kinetic variation events, some of which strongly associate with known modification events, while others represent putative chemically modified sites of unknown types.

Indexed as

DNA, BacterialDNA, MitochondrialEscherichia coliGuanosineHumansKineticsOxidation-ReductionSequence Analysis, DNA8-hydroxyguanosineDNA, BacterialDNA, MitochondrialGuanosine

Identifiers

PMID23093720
PMCPMC3530673

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.