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Research: Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes
- Chun-Long Chen,
- Aurélien Rappailles,
- Lauranne Duquenne,
- Maxime Huvet,
- Guillaume Guilbaud,
- Laurent Farinelli,
- Benjamin Audit,
- Yves d'Aubenton-Carafa,
- Alain Arneodo,
- Olivier Hyrien,
- and Claude Thermes
Genome Res. April 2010 20: 447-457; Published in Advance January 26, 2010, doi:10.1101/gr.098947.109
...increase in late-replicating regions (Watanabe et al. 2002; Stamatoyannopoulos et al. 2009). It was proposed that the increase in mutation rates in non-CpG and CpG sites results from a single mechanism, namely, an increase of DNA damage during replication (Stamatoyannopoulos et al. 2009). However...
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Research: DNA methylation epitypes highlight underlying developmental and disease pathways in acute myeloid leukemia
- Brian Giacopelli,
- Min Wang,
- Ada Cleary,
- Yue-Zhong Wu,
- Anna Reister Schultz,
- Maximilian Schmutz,
- James S. Blachly,
- Ann-Kathrin Eisfeld,
- Bethany Mundy-Bosse,
- Sebastian Vosberg,
- Philipp A. Greif,
- Rainer Claus,
- Lars Bullinger,
- Ramiro Garzon,
- Kevin R. Coombes,
- Clara D. Bloomfield,
- Brian J. Druker,
- Jeffrey W. Tyner,
- John C. Byrd,
- and Christopher C. Oakes
Genome Res. May 2021 31: 747-761; Published in Advance March 11, 2021, doi:10.1101/gr.269233.120
...methylation arrays, which provide the DNA methylation levels of CpG dinucleotides primarily in promoter and regulatory regions (Bibikova et al. 2011). We reduced the data based on overall variance using the 500 most variable probes for cluster analysis and performed unsupervised k-medoids-based clustering...
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Research: APOBEC3A drives deaminase mutagenesis in human gastric epithelium
- Yohan An,
- Ji-Hyun Lee,
- Joonoh Lim,
- Jeonghwan Youk,
- Seongyeol Park,
- Ji-Hyung Park,
- Kijong Yi,
- Taewoo Kim,
- Chang Hyun Nam,
- Won Hee Lee,
- Soo A Oh,
- Yoo Jin Bae,
- Thomas M. Klompstra,
- Haeun Lee,
- Jinju Han,
- Junehwak Lee,
- Jung Woo Park,
- Jie-Hyun Kim,
- Hyunki Kim,
- Hugo Snippert,
- Bon-Kyoung Koo,
- and Young Seok Ju
Genome Res. October 2025 35: 2158-2172; Published in Advance August 26, 2025, doi:10.1101/gr.280338.124
...editing deviated from SBS2 associated with DNA mutations and also varied between A3A and A3B (Fig. 2H,J). Briefly, (1) both A3A and A3B exhibited reduced specificity for the UpCpU context (TpCpT in DNA). However, (2) A3A displayed enhanced specificity for the UpCpG context (TpCpG in DNA), and (3) A3B...
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LETTER: CpG methylation is targeted to transcription units in an invertebrate genome
- Miho M. Suzuki,
- Alastair R.W. Kerr,
- Dina De Sousa,
- and Adrian Bird
Genome Res. May 2007 17: 625-631; Published in Advance April 9, 2007, doi:10.1101/gr.6163007
...methylation varies in different organisms. In mammalian cells the pattern consists of long tracts of DNA in which CpGs are methylated to a high average level (∼80%) punctuated by short unmethylated regions called “CpG islands” ( Bird 1986 , 2002 ). CpG islands are GC-rich in base composition and have a CpG...
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Research: Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis
- Ozren Bogdanović,
- Steven W. Long,
- Simon J. van Heeringen,
- Arie B. Brinkman,
- Jose Luis Gómez-Skarmeta,
- Hendrik G. Stunnenberg,
- Peter L. Jones,
- and Gert Jan C. Veenstra
Genome Res. August 2011 21: 1313-1327; Published in Advance June 2, 2011, doi:10.1101/gr.114843.110
...Tables S1–S5). These numbers are comparable to those observed in human cells with a similar enrichment and sequencing approach (Serre et al. 2009). The identified DNA methylation peaks are enriched for CpG dinucleotides when compared to the average, whereas their GC content is only marginally higher than...
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Method: Methyl-SNP-seq reveals dual readouts of methylome and variome at molecule resolution while enabling target enrichment
- Bo Yan,
- Duan Wang,
- Romualdas Vaisvila,
- Zhiyi Sun,
- and Laurence Ettwiller
Genome Res. November/December 2022 32: 2079-2091; Published in Advance November 4, 2022, doi:10.1101/gr.277080.122
...-in control, we estimated the bisulfite conversion rate of Methyl-SNP-seq to be 97.5%. Overall CpG methylation is at 45.3% for both replicates in line with the two ENCODE data sets analyzed showing 45.5% and 50.1% overall CpG methylation, respectively. The GC bias of Methyl-SNP-seq follows closely the known...
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Method: Discovery of an unusually high number of de novo mutations in sperm of older men using duplex sequencing
- Renato Salazar,
- Barbara Arbeithuber,
- Maja Ivankovic,
- Monika Heinzl,
- Sofia Moura,
- Ingrid Hartl,
- Theresa Mair,
- Angelika Lahnsteiner,
- Thomas Ebner,
- Omar Shebl,
- Johannes Pröll,
- and Irene Tiemann-Boege
Genome Res. March 2022 32: 499-511; Published in Advance February 24, 2022, doi:10.1101/gr.275695.121
...the variants also in the context of the 5′ and 3′ base adjacent to the variant shows that the main substitutions were strong-to-weak transitions in the context of CpG sites (VCG). Further, the comparison of our observed mutational signature with COSMIC indicates an overlap of ∼51% of the variants explained...
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Research: Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors
- J. Keith Killian,
- Lambert C.J. Dorssers,
- Britton Trabert,
- Ad J.M. Gillis,
- Michael B. Cook,
- Yonghong Wang,
- Joshua J. Waterfall,
- Holly Stevenson,
- William I. Smith, Jr.,
- Natalia Noyes,
- Parvathy Retnakumar,
- J. Hans Stoop,
- J. Wolter Oosterhuis,
- Paul S. Meltzer,
- Katherine A. McGlynn,
- and Leendert H.J. Looijenga
Genome Res. November 2016 26: 1490-1504; Published in Advance October 20, 2016, doi:10.1101/gr.201293.115
.... ECs demonstrate a striking convergence of both CpG and CpH (non-CpG) methylation with pluripotent states; the pluripotential methyl-CpH signature crosses species boundaries and is distinct from neuronal methyl-CpH. EC differentiation to TE and YST entails reprogramming toward the somatic state...
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Method: Quantification of GC-biased gene conversion in the human genome
- Sylvain Glémin,
- Peter F. Arndt,
- Philipp W. Messer,
- Dmitri Petrov,
- Nicolas Galtier,
- and Laurent Duret
Genome Res. August 2015 25: 1215-1228; Published in Advance May 20, 2015, doi:10.1101/gr.185488.114
...mechanisms causing gBGC in humans. It is known that the methylation of cytosines at CpG sites is responsible for their hypermutability: The spontaneous deamination of 5-methylcytosine causes the formation of G/T mismatches in DNA that, if not repaired, lead to G:C → A:T mutations in the next round of DNA...
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Method: A flexible method for estimating the fraction of fitness influencing mutations from large sequencing data sets
- Sunjin Moon and
- Joshua M. Akey
Genome Res. June 2016 26: 834-843; Published in Advance April 14, 2016, doi:10.1101/gr.203059.115
...estimates of f in CpG compared with gBGC or NCB sites (Wilcoxon text, P < 10−16) (Supplemental Fig. S8) suggests that CpG hypermutability (Shen et al. 1992) is a potent source of deleterious nonsynonymous mutations. Consistent with this hypothesis, nonsynonymous SNVs in CpG sites have significantly higher...

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