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Identification of epigenetic modifications that contribute to pathogenesis in therapy-related AML: Effective integration of genome-wide histone modification with transcriptional profiles.

Overview of attention for article published in BMC Medical Genomics, May 2015
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3 tweeters

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Title
Identification of epigenetic modifications that contribute to pathogenesis in therapy-related AML: Effective integration of genome-wide histone modification with transcriptional profiles.
Published in
BMC Medical Genomics, May 2015
DOI 10.1186/1755-8794-8-s2-s6
Pubmed ID
Authors

Yang, Xinan Holly, Wang, Bin, Cunningham, John M

Abstract

Therapy-related, secondary acute myeloid leukemia (t-AML) is an increasingly frequent complication of intensive chemotherapy. This malignancy is often characterized by abnormalities of chromosome 7, including large deletions or chromosomal loss. A variety of studies suggest that decreased expression of the EZH2 gene located at 7q36.1 is critical in disease pathogenesis. This histone methyltransferase has been implicated in transcriptional repression through modifying histone H3 on lysine 27 (H3k27). However, the critical target genes of EZH2 and their regulatory roles remain unclear. To characterize the subset of EZH2 target genes that might contribute to t-AML pathogenesis, we developed a novel computational analysis to integrate tissue-specific histone modifications and genome-wide transcriptional regulation. Initial integrative analysis utilized a novel "seq2gene" strategy to explore largely the target genes of chromatin immuneprecipitation sequencing (ChIP-seq) enriched regions. By combining seq2gene with our Phenotype-Genotype-Network (PGNet) algorithm, we enriched genes with similar expression profiles and genomic or functional characteristics into "biomodules". Initial studies identified SEMA3A (semaphoring 3A) as a novel oncogenic candidate that is regulated by EZH2-silencing, using data derived from both normal and leukemic cell lines as well as murine cells deficient in EZH2. A microsatellite marker at the SEMA3A promoter has been associated with chemosensitivity and radiosensitivity. Notably, our subsequent studies in primary t-AML demonstrate an expected up-regulation of SEMA3A that is EZH2-modulated. Furthermore, we have identified three biomodules that are co-expressed with SEMA3A and up-regulated in t-AML, one of which consists of previously characterized EZH2-repressed gene targets. The other two biomodules include MAPK8 and TATA box targets. Together, our studies suggest an important role for EZH2 targets in t-AML pathogenesis that warrants further study. These developed computational algorithms and systems biology strategies will enhance the knowledge discovery and hypothesis-driven analysis of multiple next generation sequencing data, for t-AML and other complex diseases.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 8%
Unknown 12 92%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 15%
Student > Bachelor 2 15%
Student > Ph. D. Student 2 15%
Student > Master 1 8%
Lecturer 1 8%
Other 0 0%
Unknown 5 38%
Readers by discipline Count As %
Medicine and Dentistry 3 23%
Agricultural and Biological Sciences 2 15%
Nursing and Health Professions 1 8%
Biochemistry, Genetics and Molecular Biology 1 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 8%
Other 0 0%
Unknown 5 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 06 June 2015.
All research outputs
#12,697,949
of 16,639,069 outputs
Outputs from BMC Medical Genomics
#609
of 879 outputs
Outputs of similar age
#153,052
of 238,725 outputs
Outputs of similar age from BMC Medical Genomics
#5
of 5 outputs
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So far Altmetric has tracked 879 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
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