TOPIC:-ENCODE PROJECT

SUBMITTED BY:- PRITI PAL MSc (BT) III SEM A7100213018

INTRODUCTIONThe ENCODE Project was planned as a follow-up to the Human Genome Project. The Human Genome Project sequenced the DNA that makes up the human genome; the ENCODE Project seeks to interpret this sequence. Coinciding with the completion of the Human Genome Project in 2003, the ENCODE Project began as a worldwide effort involving more than 30 research groups and more than 400 scientists.The approximately 20,000 genes that provide instructions for making proteins account for only about 1 percent of the human genome. Researchers embarked on the ENCODE Project to figure out the purpose of the remaining 99 percent of the genome. Scientists discovered that more than 80 percent of this non-gene component of the genome, which was once considered “junk DNA,” actually has a role in regulating the activity of particular genes (gene expression).

WHAT IS ENCODE PROJECT? The human genome encodes the blueprint of life, but the

function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

fig:- The Organization of the ENCODE Consortium.

GOALS1) The primary goal of the ENCODE project is to determine the role of the remaining component of the genome, much of which was traditionally regarded as "junk" (i.e. DNA that is not transcribed).2) It is to link variations in the expression of certain genes to the development of disease.

3) Build a comprehensive parts list of functional elements in the human genome, including element that act at the protein and RNA levels, and regulatory element that control that and circumstances in which a gene is active. 

PHASES OF ENCODE PROJECT

ENCODE is implemented in three phases:

1. pilot phase

2. technology development phase

3. production phase.

THE PHASES OF ENCODE PROJECTAlong the pilot phase, the ENCODE Consortium evaluated strategies for identifying various types of genomic elements. The goal of the pilot phase was to identify a set of procedures that, in combination, could be applied cost-effectively and at high-throughput to accurately and comprehensively characterize large regions of the human genome. The pilot phase had to reveal gaps in the current set of tools for detecting functional sequences, and was also thought to reveal whether some methods used by that time were inefficient or unsuitable for large-scale utilization. Some of these problems had to be addressed in the ENCODE technology development phase (being executed concurrently with the pilot phase), which aimed to devise new laboratory and computational methods that would improve our ability to identify known functional sequences or to discover new functional genomic elements. The results of the first two phases determined the best path forward for analysing the remaining 99% of the human genome in a cost-effective and comprehensive production phase.

ENCODE DATA PRODUCTION AND INITIAL ANALYSES Since 2007,encode has developed method and

performed a large number of sequence-based studies to map functional element across the human genome.

The element mapped (and approaches used) include RNA transcribed regions (RNA –seq, CAGE,RNA –PET and

manual annotation) Protein-coding regions ( mass spectrometry) Transcription-factor –binding sites (ChIP-seq and Dnase-

seq) Chromatin structure (DNase FAIRE-seq, histone ChIP-

seq) DNA methylation sites (RRBS assay)

FUTURE PERSPECTIVES

An important future goal will be to enlarge this dataset to additional factors, modifications and cell types, complementing the other related projects in this area (e.g., Roadmap Epigenomics Project and International Human Epigenome (HEP) Consortium). These projects will constitute foundational resources for human genomics, allowing a deeper interpretation of the organization of gene and regulatory information and the mechanisms of regulation and thereby provide important insights in human health and disease.

LIMITATIONS OF ENCODE ANNOTATION

Cell types-physiologically and genetically in homogeneous

Local micro-environment in culture may also vary

Use of DNA sequencing to annotate functional genomic features in also constrained

Considerable quantitative variation in the signal strength along the genome

CHALLENGES OF ENCODE PROJECT Adult human body contains several hundred

distinct cell types. Each of which expresses a unique subset of the

1,800 TFs encoded in the human genome. Brain aloe contains thousand of types of neurons

that are likely to express not only different sets of TFs but also a larger variety of non- coding RNAs.

A truly comprehensive atlas of human functional elements is not practical with current technologies.

APPLICATION OF ENCODE PROJECT To identify all functional elements in the

human genome sequence. It deals with the scientific and medical

communities to interpret the human genome sequence.

It also help in determining the regulatory element that control cells and circumstances in which a gene is active.

It is an integrated part which helps in finding out the non-coding and coding sequence.

OUTCOMES Understanding of the human genome The broad coverage of ENCODE annotation

component understanding of common diseases with a genetic component rare genetic diseases

119 of 1,800 known transcription factors and13 of more than 60 currently known histone or DNA modification across 147 cell types

Overall these data reflect a minor fraction of the potential functional information encoded in human genome.

FUTURE GOAL OF ENCODE PROJECT Mechanistic process that generate these

elements and how and where they function. Enlarge the data set to additional factors,

modifications and cell types, complementing the other relate projects.

Constitute foundational resources for human genomics, allowing a deeper interpretation of the organization of gene and regulatory information and the mechanisms of regulation and thereby provide important insights into hum an health and disease.