Keynote: George Church - BI/O: Reading and... - ISMB2010

George Church has developed an amazing amount of technology. - Barb Bryant

I am always wondering that if he gets any sleep at all. - Dawei lin

Which is the introducer? - Dawei lin

michal linial, if I'm not wrong (which I was, need new glasses) - arne

The My First DNA sequencer reference: http://www.wired.com/wired... - Shannon McWeeney

First challenge on computational interpretation and integration: personal genomes =stem cell epigenome + mC environments + traits. - Dawei lin

Olga Troyanskaya - Barb Bryant

Cost of drugs goes up linearly; cost of sequencing is dropping exponentially - Barb Bryant

40,000 fold price drop for 4 years - Dawei lin

CGI price for genome is $1500/year? - Dawei lin

In 2005 we abandoned a monopolistic capillary electrophoresis; instead we have a couple and now 21 different technologies for sequencing. Resulted in a jump in rate of change of sequencing capacity - Barb Bryant

He thinks that many of the sequencing companies will find a niche :) - arne

Cost of personal genome: 2007: $57M; 2009 $1500, for 40-fold coverage. - Barb Bryant

Close to the $1000 genome - arne

(+ $100,000 interpretation cost?) (he doesn't really think that) - Barb Bryant

Drmanac et al Science Jan 2010 - Dawei lin

Sidetrack: One friend said when he started his PhD it took 6 month to sequence a bacteria and 6-60 month to analyse it. Not it takes 6 minuted to sequence it and still 6-60 month to analyze it. - arne

limitation is several hundreds nm in scale on chip (positive charge molecules on hydrophobic background - Dawei lin

7% human genome is missing so far because of technical challenges - Dawei lin

trio genomics information (father, mother, child) is increasing important in genomics research - Dawei lin

From open acess Sequences to Bio-Fab - arne

One of the 21 sequencing technologies is open-access. Reads and writes DNA with light. - Barb Bryant

2nd-gen synthesis ($500 per 15 Mbp) - arne

Second-generation synthesis - four different kinds of technologies. - Barb Bryant

Next Gen synthesis: off chips $500 15Mbp - Dawei lin

Tian et al 2004 Nature - arne

The work started around 2003 - Dawei lin

personalgenomics.org - arne

person genome 3M allele -> immunology + microbome -> trait - Dawei lin

Issues of personal identification from genomic data. Informed consent as one solution. - Barb Bryant

Have 16,000 volunteers for Personal Genome Project so far; 100,000 target. - Barb Bryant

Claims that ~1800 genes are highly predictive and medically actionable. - Barb Bryant

They are rare but collective common at 10% level - Dawei lin

Example of the Madsen family with two diseases. Found causative allelles - 4 total (2 from each parent). - Barb Bryant

evidence.personalgenomics.org - Dawei lin

Each time we find a scary allele in a person, it could be a sequencing error; it could be a problem with the literature. - Barb Bryant

found a dozen cases in the literature got allele sequence wrong - Dawei lin

The oldest volunteer for PGP is 96.7 years old - Dawei lin

Q: Are these genomes available ? - arne

Circulating tumor, pathogen, fetal, and immune cells. - Barb Bryant

Microbe vs Immunome - arne

If you want to look for a microorganism in a body, you can either look directly for the microbe, or look for the body's reaction. - Barb Bryant

immune test is to focus on response to exposure. - Dawei lin

Sequencing after vaccination - response is maximum after 7 days - arne

Generating human tissue from pluripotent stem cells - Barb Bryant

The Economist 20-May-2010 cover - Dawei lin

Genome engineering - Barb Bryant

E.g., change the genetic code -- for resistance to pathogens, new amino acids, and something else. - Barb Bryant

You have to do this safely. - Barb Bryant

For $400M, Dupont made 27 changes to the 4.6 Mbp E. coli, to make a chemical. - Barb Bryant

Another application: bio-petroleum from microbes. - Barb Bryant

Identify enzymes that synthesize alkane. Many cyanobacteria made trace amounts; others made none. Did genome sequence "subtraction" to find which genes were in the former. Isolated & tested these genes. Overproduced them; it worked. Green chemistry. - Barb Bryant

Multiplex Automated Genome Engineering (MAGE)... - Barb Bryant

Church's own genome is available: http://www.personalgenomes.org/public... - Christiaan Klijn

So: subtract my genome from Church's, then overproduce those genes --> TOTAL BRILLIANCE! - Barb Bryant

Example of freeing up a codon by changing those codons to a different one./ - Barb Bryant

Is this not just the analysis. Not the sequence ? (or did I miss a link) - arne

See the 'Datasets' header -> you can get 500k Affy data as well as exome - Christiaan Klijn

Metabolic engineering example. Historically, you'd get obsessed with one step in the pathway and overproduce one enzyme. But then you'd get product inhibition, or the product might be toxic. - Barb Bryant

Would be nice with a map to the reference genome as well, but guess that can be done - arne

DNA Nanostructures: (DNA origami). Proposes a combination of DNA and proteins. - arne

DNA nanostructures help solve structures of membrane proteins. - Barb Bryant

First practical application: Made a long rod that was stiffer than other DNA. Used in NMR for membrane proteins (Cooooll idea but, it has been tried with proteins before) - arne

caDNAno is a software tool that is free available - Dawei lin

Time for questions. - arne