Saturday, July 17, 2010

AHEAD(the Alliance for Human Epigenomics and Disease)

I found from last paper that Epigenome Project is continued by AHEAD. In this post, I will introduce the article about AHEAD which is published in Nature.  Ah.. the funny thing is.. when I was googling about AHEAD, I found that  Prof, Young-Joon Kim presented his research in AHEAD conference in last year.


The title of article which will be introduced is "Moving AHEAD with an international human epigenome project". This was published on August in 2008.

A plan to 'genomicize' epigenomics research and pave the way for breakthroughs in the prevention, diagnosis and treatment of human disease.


here we discuss the benefits of the AHEAD frame work to coordinate and plan an international Human Epigenome Project.

Epigenetic mechanisms : histone modification, positioning of histone variants, nucleosome remodelling, DNA methylation, small and non-coding RNAs. These things interact with transcription factor or other protein to regulate target gene expression.
epigenetic mechanisms are recognized as being involved disease.
although this mechanisms have heritable characteristics, drug can reverse them.
So more comprehensive characterization of them is needed to maximize utility of them in treatment of disease.
the goal of AHEAD project is provide high-resolution reference epigenome maps.
an international project would provide the bioinformatics tool.

-Early steps- 

About from 2004 global movements were appeared to organize the international community.
In Europe, strong tradition for epigenetic study supported by European Union funding programmes or individual national initiatives. more than US $79M was supported to DNA methylation(HEP, Human Epigenome Project), chromatin profiling(HEROIC,High-Throughput Epigenetic Regulatory Organization In Chromatin) and treatment of neoplastic disease(EPITRON, EPIgenetic TReatment Of Neoplastic disease). The special function is provided by the NoE(Epigenome Network of Excellence).
In U.S. 2004 NCI(international cancer institute)-sponsored Epigenetic Mechanisms in Cancer Think Tank, 2005 NCI workshop, AACR(The Ametican Association for Cancer Research) organized a Human Epigenome Workshop in 2005, 2006.
On the heels of these workshop AACR Human Epigenome Task Force was formed to design strategy and develop a timetable for the implementation of an international Human Epigenome Project. This task force recommended the formation of AHEAD to coordinate a transdisciplinary, international project.


In summary, each country (EU, US) organize and develop their own community and project. And after Human peigenome workshop from AACR, AACR Human Epigenome Task Force was formed and they made AHEAD, internation project to map a defined subject of robust epigenetic makers and support bioinformatics infrastructure.


-The scope of AHEAD-


1.provide complete epigenome maps at very high resolution for important histone modifications across diverse cellular states in both human and mouse
2.complete and catalogue epigenome maps of model yeasts, plants, and animals
3.deliver a high resolution DNA methylation map of the entire human genome in defined cell types and a landmark map for transcription start sites of all protein coding genes and a representative number of other features throughout the genome
4.define non-coding and small RNAs
5.establish a bioinformatics platform including a relational database, website and suite of analytic tools to organize, intergrate and display whole epigenomic data on model organisms and humans.
AHEAD differ from and complement ENCODE(ENCyclopedia Of DNA Elements).
ENCODE is focused on defining the functional sequences in the genome.
AHEAD define the patterns of epigenetic regulation at that sequences.


-Reference epignomes-

The criteria for selection of the reference system:
1.cells should be easy to sample in a reporoducible fashion.
2.cell numbers should be sufficient for analyses of DNA methylation and chromatin modifications.
3.cell progenitors should be identified that can be suitably manipulated and harvested in a pure state.
4.where possible, cells should be amenable to tissue reconstruction and three-dimensional model systems
5.systems must provide insight into key differentiation and related disease states.


-Advances in technology-
there is nothing new, so I just skip this part

-Model organisms-



-Computational challenges-
A central relational database and a web interface which include analytic and statistical tools to present and visualize data are needed.

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