Evidence map›Paper›PMID 27587586›Full record

ArticleNucleic acids research2016

Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq).

Alexander R Langley, Stefan Gräf, James C Smith, Torsten Krude

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 129 citations in OpenAlex.

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  12. G-quadruplex stabilization induces DNA breaks in pericentromeric repetitive DNA sequences in B lymphocytes.Proceedings of the National Academy of Sciences of the United States of America · 2025
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Alexander R LangleyFrancis Crick Institute, Mill Hill Laboratory, The Ridgeway, London NW7 1AA, UK.
Stefan GräfDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
James C SmithFrancis Crick Institute, Mill Hill Laboratory, The Ridgeway, London NW7 1AA, UK.
Torsten KrudeDepartment of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK tk218@cam.ac.uk.
The Francis Crick Institute · GBUniversity of Cambridge · GB

Funding

Medical Research Council MC_U117597140
6 · The paper itself

Abstract

Next-generation sequencing has enabled the genome-wide identification of human DNA replication origins. However, different approaches to mapping replication origins, namely (i) sequencing isolated small nascent DNA strands (SNS-seq); (ii) sequencing replication bubbles (bubble-seq) and (iii) sequencing Okazaki fragments (OK-seq), show only limited concordance. To address this controversy, we describe here an independent high-resolution origin mapping technique that we call initiation site sequencing (ini-seq). In this approach, newly replicated DNA is directly labelled with digoxigenin-dUTP near the sites of its initiation in a cell-free system. The labelled DNA is then immunoprecipitated and genomic locations are determined by DNA sequencing. Using this technique we identify >25,000 discrete origin sites at sub-kilobase resolution on the human genome, with high concordance between biological replicates. Most activated origins identified by ini-seq are found at transcriptional start sites and contain G-quadruplex (G4) motifs. They tend to cluster in early-replicating domains, providing a correlation between early replication timing and local density of activated origins. Origins identified by ini-seq show highest concordance with sites identified by SNS-seq, followed by OK-seq and bubble-seq. Furthermore, germline origins identified by positive nucleotide distribution skew jumps overlap with origins identified by ini-seq and OK-seq more frequently and more specifically than do sites identified by either SNS-seq or bubble-seq.

Indexed as

DNA ReplicationGenome, HumanHigh-Throughput Nucleotide SequencingReplication OriginCell Line, TumorChromosome MappingComputational BiologyDNAGenomicsHumansNucleotide MotifsSequence Analysis, DNATranscription Initiation SiteDNAOkazaki fragments

Identifiers

PMID27587586
PMCPMC5137433
OpenAlexW2509863861

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.