The public data repository "Encyclopedia of DNA Elements" is about to complete. What is ENCODE's next plan?

In April 2003, scientists from various countries cooperated to complete the major task of sequencing the first draft of the human genome
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It reveals one point: only 1% of the human genome is responsible for coding genes, which poses a challenge to the just-starting genomics community-what is the function of the remaining 99%? In the next 18 years, the Encyclopedia of DNA Elements (ENCODE) project attempted to explain this treasure trove of genomic data by comprehensively describing all functional elements in DNA, including genes and non-coding elements that regulate gene activity

The ENCODE Alliance is funded by the National Human Genome Research Institute (NHGRI) and consists of 31 institutions, including the Massachusetts Institute of Technology and the Board Institute of Harvard University
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The alliance revealed how genes are regulated in the human and mouse genomes

At the Board Institute, the project is led by Bradley Bernstein, a member of the institute, who is the Dana-Farber Cancer Institute (Dana-Farber Cancer Institute) Gene Regulation Observation and Epigenome Project (Gene Regulation Observatory and Epigenomics Program) director, chair of the Department of Cancer Biology, as well as Charles Epstein and Noam Shoresh (Noam Shoresh), they are all associate directors of the Epigenomics Project
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For the past 13 years, they have led a team of scientists and project managers who have contributed hundreds of experiments and thousands of data sets to this collective effort

Now, ENCODE is coming to an end in its fourth and final work phase, and what follows is a new project that will build on ENCODE’s existing foundation: the effect of genomic variation on function (IGVF) will in-depth study of DNA elements Functions and how they function in different cell types and states
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Epstein introduced ENCODE's current status, impact and what will happen next
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Main goals of ENCODE

ENCODE was and is a project dedicated to understanding the function of the genome
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It uses a series of technologies developed after genome sequencing.
The goal is to develop and apply these new methods to understand the functional significance of each part of the genome

We need to go beyond gene sequencing to map the functional elements of gene regulation

ENCODE's biggest impact

The most profound impact of this project is that it enables the interface between the functional identification community and the genetics community.
These are two parallel efforts

Therefore, most of the genetic variants that may make people susceptible to certain genetic diseases, such as Alzheimer's disease, cardiovascular disease, and diabetes, are consistent with the regulatory regions discovered by projects such as ENCODE
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These sites are called enhancers-remote regulatory elements that affect gene expression, and may be far away in the genome

Another exciting insight is related to the three-dimensional structure of chromosomes as we know it and the pathological conditions that may result when this structure is destroyed
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DNA is highly compressed to fit the nucleus and has so-called topologically associated domains (TADs), which are the key to achieving gene regulation

Next plan

Board is interested in genomic medicine because we want to cure and prevent diseases, so we really need to delve into the details of how it works
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The National Human Genome Research Institute (NHGRI) has funded a new alliance called "The Effects of Gene Variation on Function" (IGVF), and Board is working hard to initiate a role in the new alliance
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This new research will further develop functional annotations for a deeper understanding of genetics, and take it to a new level by using single-cell methods instead of merging the various cell types that make up tissues as in the past
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We are entering a beautiful new world of single-cell multi-omics, where we will describe gene expression, the functional state of the genome, and a wealth of regulatory elements from the same single cell
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