historical costs to sequence the 3 billion bp of a human genome

two vendors competition

costs to sequence a human genome

4

5

6

7

8

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10

1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009

year sequenced

log

10 (

US

do

llar

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$3 billion

$300 million

$300,000

Gordon Moore

BGI Offers Next-Gen Sequencing Service: Kicks Off 100-Genome Sequencing Project [8 January 2008]

Knome, BGI Forge Sequencing Alliance; GATC Spins Off Personal Genomics Unit [January 15 2008]

1 million SNPs580,000 SNPs

Google

whole genome

BGI-Shenzhen

Emperor’s Yan and Huang were the first rulers of ancient China, so modern Chinese say that they are descendants of YanHuang.

The panda is a Chinese national treasure and the logo for the World Wildlife Fund. While not the first endangered species to be sequenced (chimp was first), it will be the first with a conservation focus.

Whole genome shotgun assembly is non-trivial for 35 bp reads even with paired end information and 50x redundancy.

YanHuang and the panda genome (raising awareness for the new technologies)

Nature: 17 January 2008 Science: 25 January 2008

BGI-Shenzhen and allies in the US and UK will be sequencing 1000 human genomes in the next 3 years

expressed gene sequences of 1000 medicinal plants for only $2 million

There are 96 plant species with more than 20,000 expressed sequence tags (ESTs), but most are crop plants. If we count only medicinal plants, generously defined to include makers of secondary metabolites with purported health benefits, such as lycopene for tomatoes and resveratrol for grapes, there are 16 plant species with more than 20,000 ESTs. If we use a strict definition of medicinal, there are just 4 plant species with more than a mere 5000 ESTs. They are artemesia, Madagascar periwinkle, gingko, and ginseng.

the triad of biological causation

human genome

gene hunts vs synthetic biology

environmental factors

questionnaires vs molecular detection

infectious agentscultures vs

metagenomics

http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA

Among individuals of Ashkenazi Jewish descent, researchers have found that about 2.3 percent have an altered BRCA1 or BRCA2 gene. This frequency is about 5 times higher than that of the general population.

http://www.who.int/mediacentre/factsheets/fs297/en/index.html

One-fifth of cancers worldwide are due to chronic infections, mainly from hepatitis B viruses HBV (causing liver), human papilloma viruses HPV (causing cervix), Helicobacter pylori (causing stomach), schistosomes (causing bladder), the liver fluke (bile duct) and human immunodeficiency virus HIV (Kaposi sarcoma and lymphomas).

we can cure, eradicate, or at least treat almost all infectious diseases

metagenomics: DNA sequencing analysis of viral and microbial worlds

without requiring a pure culture

we have little information on the vast majority of viral and microbial species because of our inability to culture them in the lab; the estimate is fewer than 1% have been cultured

classical methods

known sequence grow as a pure culture

molecular biologytargeted

amplification

biological sample

metagenomics

partial purification (e.g.

by size)

just sequence it

biological sample

metagenomics of the “virome”

human specimen

0.45 m filter

viral particles

DNA RNA

virome sequence

tangential flow filter, high speed centrifuge

viral genomes (103 bp) are very small compared to bacterial (106 bp) or human (109 bp) genomes and it helps to remove non-viral contamination

February 6, 2008 (10.1056/NEJMoa073785)

A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases

Gustavo Palacios, Julian Druce, Lei Du, … and W. Ian Lipkin

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York; Victorian Infectious Diseases Reference Laboratory, Victoria, Australia; 454 Life Sciences, Branford, CT; Centers for Disease Control and Prevention, Atlanta.

Viral and bacterial cultures; polymerase-chain-reaction assays for known pathogens; viral and panmicrobial microarrays revealed no plausible candidates.

However, BLASTX analysis of the deduced proteins for 94,043 reverse transcribed sequences revealed 14 fragments consistent with Old World arenaviruses.

22 February 2008: Vol. 319. no. 5866, pp. 1096 - 1100

Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma

Huichen Feng, Masahiro Shuda, Yuan Chang, Patrick S. Moore

Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 1.8, Pittsburgh, PA 15213, USA.

99.4% of 382,747 tumor derived sequences aligned to human RefSeq RNA, mitochondrial, assembled chromosomes, or immunoglobulin sequences. Two sequences were used to define a previously unknown human polyomavirus.

proof of causation and other steps after candidate pathogen is identified

metagenomics of idiopathic inflammatory diseases is a high-risk extremely-high-payoff activity, but there is a low-risk moderately-high-payoff activity that will put Alberta “on the map” internationally

disease tissue

viral fragment

genome sequence

compound screening

develop diagnostics

population case-controls

develop treatments

genome synthesis

develop vaccines

synthesis costs $0.50 per bp

computationally accelerated