Liveblogging the Foresight 2010 Conference – First Larry Millstein one DNA sequencing

The Foresight 2010 conference in today and tomorrow

Free live webcast at:
Follow the conference on Twitter: #Foresight2010

The first speaker is Larry Millstein who is speaking on Sequencing Single DNA molecules.

Larry is going through an initial tutorial on DNA, DNA replication and DNA sequencing.

Here is an online tutorial on the steps of DNA replication (by someone else)

Here is DNA replication at wikipedia

DNA polymerase at wikipedia

DNA template is described at Yale

* a couple of slides on the massive progress and fast rate of progress in lowering the cost of Genome sequencing and sequencing 1 million base pairs
* a series slides on the steps for DNA sequencing
* long reads versus short reads (7X coverage for long reads and 20X coverage for short reads, but future advance will likely erase this difference)

Illumina is a leader and their latest machine costs $650,000 and generates 25 billion base pair sequences per day (8X coverage of the human genome, so one good read of a full genome per day)

10 terabases per year, 200 HGE (human genome equivalents) per machine

Beijing Genomics Institute bought 200 machines and now has a capacity of 2 petabases per year.


21-28 gigabases/run
takes 8 days to do a run

Pacific Biosciences
The theoretical limit of real time single molecule sequencing.

Work is done in zero waveguides. (ZMW)
The ZWV are about 50 nanometers around and can hold 600,000 molecules. (20 X 10^-21 liters)

Put DNA into the ZMW covalently.

The DNA bonds briefly to the bottom connection point where the flourescent attached can put a single that can be read. About 100 reads per second. The DNA that is flying free has flourescents too but are moving around too fast to give a signal.

No commercial model yet
expected sub-$1000 genome sequencing
sub 1 HGE in 4 hours
Maybe much better


Real time single molecule sequencing.
No fabrication of ZMW wells
Forster Energy Transfer

commercial device for 2011
sub-$1000 HGE
4 hour for HGE

Cracker (Taiwan company)

CMOS technology

Beyond Real Time Single Model Sequecing
Direct sequencing

Nanopore sequencing
figure out which base pair is passing through a pore in a membrane

EM Sequencing
use an electron microscope

AFM sequencing
use STEM and AFM
Applications of NexGen Sequencing

Whole genome sequencing – human variation, disease risk
Genome scanning – cancer SNPs
Populations wide genomic sequecing -HIV variants
Ancient DNA sequencing – Neanderthal etc…
synthetic biology

Metagenomics potential
Figure out the big genomics and biological picture for whole planet/biosphere


DNA Polymerase has one in a million error rate. Need to error check.

Is an ensemble sometimes better than one ?

Can single molecule SBS be used as the read out for computational devices based on DNA ?

Can single molecule SBS be used as the basis for programmable molecular assemblers ?