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Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing

Overview of attention for article published in Nature, May 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (59th percentile)

Citations

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377 Dimensions

Readers on

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518 Mendeley
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11 CiteULike
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Title
Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing
Published in
Nature, May 2014
DOI 10.1038/nature13268
Pubmed ID
Authors

Volker Hovestadt, David T. W. Jones, Simone Picelli, Wei Wang, Marcel Kool, Paul A. Northcott, Marc Sultan, Katharina Stachurski, Marina Ryzhova, Hans-Jörg Warnatz, Meryem Ralser, Sonja Brun, Jens Bunt, Natalie Jäger, Kortine Kleinheinz, Serap Erkek, Ursula D. Weber, Cynthia C. Bartholomae, Christof von Kalle, Chris Lawerenz, Jürgen Eils, Jan Koster, Rogier Versteeg, Till Milde, Olaf Witt, Sabine Schmidt, Stephan Wolf, Torsten Pietsch, Stefan Rutkowski, Wolfram Scheurlen, Michael D. Taylor, Benedikt Brors, Jörg Felsberg, Guido Reifenberger, Arndt Borkhardt, Hans Lehrach, Robert J. Wechsler-Reya, Roland Eils, Marie-Laure Yaspo, Pablo Landgraf, Andrey Korshunov, Marc Zapatka, Bernhard Radlwimmer, Stefan M. Pfister, Peter Lichter

Abstract

Epigenetic alterations, that is, disruption of DNA methylation and chromatin architecture, are now acknowledged as a universal feature of tumorigenesis. Medulloblastoma, a clinically challenging, malignant childhood brain tumour, is no exception. Despite much progress from recent genomics studies, with recurrent changes identified in each of the four distinct tumour subgroups (WNT-pathway-activated, SHH-pathway-activated, and the less-well-characterized Group 3 and Group 4), many cases still lack an obvious genetic driver. Here we present whole-genome bisulphite-sequencing data from thirty-four human and five murine tumours plus eight human and three murine normal controls, augmented with matched whole-genome, RNA and chromatin immunoprecipitation sequencing data. This comprehensive data set allowed us to decipher several features underlying the interplay between the genome, epigenome and transcriptome, and its effects on medulloblastoma pathophysiology. Most notable were highly prevalent regions of hypomethylation correlating with increased gene expression, extending tens of kilobases downstream of transcription start sites. Focal regions of low methylation linked to transcription-factor-binding sites shed light on differential transcriptional networks between subgroups, whereas increased methylation due to re-normalization of repressed chromatin in DNA methylation valleys was positively correlated with gene expression. Large, partially methylated domains affecting up to one-third of the genome showed increased mutation rates and gene silencing in a subgroup-specific fashion. Epigenetic alterations also affected novel medulloblastoma candidate genes (for example, LIN28B), resulting in alternative promoter usage and/or differential messenger RNA/microRNA expression. Analysis of mouse medulloblastoma and precursor-cell methylation demonstrated a somatic origin for many alterations. Our data provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis, which are probably also of importance in a wider developmental and disease context.

X Demographics

X Demographics

The data shown below were collected from the profiles of 44 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 518 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 9 2%
Germany 5 <1%
France 3 <1%
Italy 2 <1%
United Kingdom 2 <1%
Netherlands 1 <1%
Switzerland 1 <1%
Sweden 1 <1%
Canada 1 <1%
Other 5 <1%
Unknown 488 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 136 26%
Student > Ph. D. Student 117 23%
Student > Bachelor 40 8%
Student > Master 38 7%
Student > Doctoral Student 35 7%
Other 87 17%
Unknown 65 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 175 34%
Biochemistry, Genetics and Molecular Biology 127 25%
Medicine and Dentistry 81 16%
Computer Science 12 2%
Neuroscience 10 2%
Other 33 6%
Unknown 80 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 58. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 April 2017.
All research outputs
#690,878
of 24,514,423 outputs
Outputs from Nature
#26,496
of 95,259 outputs
Outputs of similar age
#6,538
of 232,160 outputs
Outputs of similar age from Nature
#409
of 1,006 outputs
Altmetric has tracked 24,514,423 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 95,259 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 101.8. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 232,160 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 1,006 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.