Paper - Review

DOI: 10.1038/nbt1010-1045

Abstraction

NIH Roadmap Epigenomics Mapping Consortium
→ to produce (a public resource) (← of epigenomics map) → to represent (the normal counter-parts of tissue & organ system) (← which frequently involved in human disease)

Introduction

❓Purely DNA sequence-level investigation
→ How (the same genome sequence) can give rise → to over 200 different cell types

⭐ Epigenesis
→ to involve (differential regulation) (← of gene & their products)

(Gene regulation) & (Genome function)
→ related to physical organization (← of genomic DNA)
→ is packed into chromatin

✒ Chromatin
← a complex nucleoprotein structure comprising (histones & DNA binding factors & accessory protein complexes & non-coding RNAs)
→ a dynamic entity (← that is subject to modification of both (its DNA & protein))

⭐ Central roles for epigenomic (← in disease & pathogenesis)

⭐ Roadmap Epigenomics Mapping Consortium
→ provide a publicly accessible resource (← of epigenomic map)

A coordinated study of human epigenomes

NIH Roadmap Epigenomics
← in 2008
→ producing a public resource of (human epigenomic data) → to catalyze (basic biology) & (disease-oriented research)

NO ❌ REFERENCE epigenome
→ the epigenomic landscape varies → across tissue types

Reference maps for major epigenomic features

(Comprehensively & Accurately) ← by high-throughput sequencing
1. DNA methylation
2. Histone modifications
3. Chromatin accessibility
4. RNA expression

✒ DNA methylation
→ by sequencing DNA (← which has been treated by BS-seq & MeDIP-seq)

✒ Histone modification
→ assayed by ChIP-seq
→ differentially modified histone tail peptides → to ensure antibody specificity

✒ Chromatin accessibility
→ assayed by (sequencing DNase I cleavage sites) (← in nuclear chromatin)
→ performed at (high ↑ sequencing depth) → to provide a global survey of accessible regions

✒ RNA expression
→ assayed by (sequencing mRNA) & (size-selected small RNA fractions)
→ to (augment & illuminate) the functional output (← of the epigenomic profiles)

Prioritized cells and tissues

→ Investigate (a diverse collection) (← of cell & tissue models)
→ (dynamics & inter-relationships) (← among epigenomic features & catalyze study) of their functions in development
→ Coverage (← of human cellular diversity) will be achieved through study (← of primary cells & tissues) → from leading health issues

⭐ Prioritized cell types
← include (liver & muscle & adipose)

Profiles (← for these diverse cell models) → offer unprecedented insight into the (breadth & dynamics) of human epigenomes

Integration and dissemination of human epigenomes

→ provide ready-access to a critical mass of high-quality epigenomic data
→ comprise (multiple levels of information) → to integrated (epigenoimc maps) (← which represent a composite of multiple epigenoimc profiles) & to capture (biological variation) across different cel types

Progress and challenges

The use of established (technologies & approaches) → enabled rapidly initiate data production

Cell type selection and acquisition

A key ongoing challenge
→ to (identification & prioritization) ( ←of cells & tissues)

Many high-value primary tissues are available in limited quantities
Isolating relatively homogeneous population (← from certain complex tissues) can involve extensive preparative steps

⭐ Our crude understanding (← of inter-individual epigenomic variation) leaves open the questions

Standardization of assays

Implementing the latest epigenomic technologies (← which based on NGS)
∵ (These technologies continue to evolve) & (These technologies are inherently dependent on preparative steps)

To (procurement & validation) of high-quality antibody reagents
∴ A need to (benchmark & standardize) different assay types

Data integration and dissemination

Challenges at the level of (data handling & analysis)
1. Clearer understanding (← of the underlying data sets) ← in terms of (sensitivity & specificity & precision)
2. The sheer volume & complexity of consortium generated data

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