Genomics• Sequencing: the data deluge• Dynamic genome vs static genome• Increase in the diversity of uses of genomic data• Foundational technology for new science • synthetic genomics and the engineering of

biologybiology

Genome I: DNA sequencing data deluge

2006-2011

2011-2015$30K Human genome

< $1K Human genome1-10Tb storage per run

10-100Tb storage per run

$3B Human genome

1998-2007

1-10Gb storage per run

- Traditionally genomic data has been stored and acc essed through a centralized repository (NCBI)

- Researchers may have to store their own data local ly in future

-As research becomes increasingly data centric there will be a requirement for structured comparison with other av ailable data on a continuous basis.. ..

Implications of data driven/data centric genomics r esearch

continuous basis.. ..

? Closed communities of users with different access privileges ?

? Reduction in complexity of search parameters …Data cubes ?..Software agents ?

Genome related information for the general user-as consumer product ?

Once the cost of comes within easy reach of individuals they can initiate its production and it s uses thus altering many of the privacy issuesuses thus altering many of the privacy issues

When in control, more likely to share it/take part in studies (drug company/social/geneological etc)

This requires a new way to present, handle and interrogate personal genome information

ENCODE: Encyclopedia of functional elements within the human genome

1) Pervasive transcription

Genome II Qualitatively different

1) Pervasive transcription2) Fewer boundaries3) More control elements4) Genome partitioned into discreet functional territories that repress or activate transcription

Genome II: The gene: Qualitatively different

Transcriptional complexity of a gene

Gingeras T. R. Genome Res. 2007;17:682-690

©2007 by Cold Spring Harbor Laboratory Press

Genome III: Epigenetics and the Genome III: Epigenetics and the “Histone code”“Histone code”

Epigenome is Dynamic-

Influenced by environmental and social forces

Associated with increasing Associated with increasing numbers of developmental

states and diseases

A model of “Lineage Choice” from a epigenetic perspe ctive

Lineage choice involves coordinated activation and

repression of blocks of genes

Your genome cant be altered but your epigenome can

Implications of a life-long dynamic epigenome?

chemical social

Signaling pathways

Epigenome

The abstraction of the Genome as linear string of DNA is now outdated and needs to be replaced with something richer to capture some of the topology and its systems dynamics

phenotype

William Sellers (1824-1905)

Biology has as a engineered technology has few standards

To deploy Biology as a constructive technology standards will be essential

Genome IV: Synthetic Biology

It is highly likely many organisms of the future whether evolving or not will come from the design

of engineers/scientists

The process will become an essential part of the outcome

Features of Synthetic Biology

Traditional techniques in genetic engineering have underpinned modern molecular biology (PCR/Recombinant DNA/cloning)

To this now can be added-Automated construction (synthesis) of DNA-Automated construction (synthesis) of DNA

- Introduction of standards underpinning their use

- Design of more complex systems other than what exists in nature will require abstraction of some o f the complexity to allow for improved design

Genomics coupled with DNA synthesis: allows for the seamless linking of information and material

Some initiatives in Synthetic BiologyTop-down and Bottom up approaches

Creation of first free-living synthetic genome (mycoplasma (2008))

The MIT Registry of Standard Biological Parts (BioBricks)(protein generators/regulators/receivers and senders/measurement devices/reporters)

The international Genetically Engineered Machine competition

Summary

- The human Genome led to the parts list

-The capacity to measure its changes in a dynamic way presents new challenges for researchers and industry alike

-Its likely that genomic related data will be collec ted and monitored for a large number of Biological systems (e.g. humans) in the future

- We are moving from observing the Genome and trying to predict its effects on Biological systems towards learning to utilize it as a technology

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