Genomics Beginning & Basis of Biotechnology The Fourth Asian Conference on Biotechnology and Development February 12-13, 2009, Kathmandu, Nepal Huanming Yang Ph.D. Beijing Genome Institute (BGI), China 1. A world of crises and opportunities 2. Two pillars and platforms of genomics 3. “Three BY ALLs” for genomics 4. Four proposals for collaboration 5. Five collaborative projects undergoing Biotechnology Challenges and opportunities for Asia for developing countries 2007-2008 Global energy crisis Global food crisis Global financial crisis Global economy crisis Crisis Crisis & Opportunity 2007: A Year of Miracle “There were more breakthroughs (in life sciences) last year (2007) than in several of the past decades combined.” Dr. Eric Topol (Scripps Institute, March 11 2008 ): The hunt for genetic gold “A Year of Miracle” “These findings are just a prelude to what's shaping up as a true conceptual and technological revolution. Just as physics shocked the world in the 20th century, it is now clear that the life sciences will shake up the world in the 21st.” Newsweek Oct. 15, 2007 2007 The Year of Sequencing Nature Methods 5:11-14, 2008 2007年的 “年度问题” Question of the Year 《自然－遗传学》杂志的编辑提出了2007年的 “年度 问题”： 如果人类基因组的测序费用降至1000美元，那 将意味着什么？ What does it mean if a human genome sequence costs less than $1000? “一千美元一个人类基因组”已经不是能不能、而是 什么时候的问题了。这样的问题在４年前还难以设想。 “$1000 Genome’ is not a question whether it is possible, but when it will be realized. It is unimaginable only 4 years ago. BREAKTHROUGH OF THE YEAR: Human Genetic Variation Equipped with faster, cheaper technologies for sequencing DNA Science and assessing variation in genomes on scales 318: 1842 – 1843 21 December 2007 ranging from one to millions of bases, researchers are finding out how truly different we are from one another Now, we have moved from asking what in our DNA makes us human to striving to know what in my DNA makes me me. Volume 22 | Issue 12 | Dec. 2008 TIME’s Best Inventions of 2008 “我们正处在个人 基因组学 (personal genomics) 革命的初 始阶段，这场革命不 仅会转变我们照顾自 己的方式，还将改变 9 Nov. 2008 我们个人信息的表现 形式。” 《时代》周刊 We are at the beginning of a personal- : genomics revolution that will transform 1. The Retail DNA Test not only how we take care of ourselves 个人 测试服务 位居榜首 but also what we mean by personal “ DNA ” information. Top 10 Medical Breakthroughs of 2008 4. Genomes for the Masses James Watson did it. So did Craig Venter. Now you, too, can map your entire genome and reveal some of its many secrets. Scientists debate whether that information is really worth anything at the moment — in many cases, there isn't enough scientific knowledge to interpret what it really means to have this gene variant or that one — but companies at least make it possible for you to take a gander at your genetic data. (Although the service was available previously, until this year, it's been prohibitively expensive.) You provide a sample of saliva, from which your DNA is extracted, copied and combed for the presence of 90 known genetic variations that code for different traits or conditions, from lactose intolerance (though you could probably drink a glass of milk and find out for far cheaper) to prostate cancer. Right now, there's no way to know whether you'll get cancer just because you have the gene, but once the science has advanced, the hope is that such genetic mining will predict disease, giving people the option of seeking treatment before they get sick. Nature favours developing countries To develop your own bioindustry by taking advantage of your rich genetic resources Genomics A science to find genes Basis and beginning of Biotechnology (biotech cannot be done without genes) 1. A world of crises and opportunities 2. Two pillars and platforms of genomics 3. “Three BY ALLs” for genomics 4. Four proposals for collaboration 5. Five collaborative projects undergoing Two Pillars of Genomics “Life is of sequence” Genetic information is in sequence ATTCGGTAACGATTAGAA DNA sequence: The essence of “life is life”! The same for plants Two Pillars of Genomics “Life is digital!” “the instructions for making a life from one generation to the next is digital, John Sulston NOT analogue …” “生命指令是数据的，而不是模拟的” 101010101010100101 010101001101010101 010100101010101001 0100111000011100000111000001100010101 0101010010101010101010100101010101001010 0111000011100000111000001100010010101010 0101010101010101001010101010010100111000 0111000001110000011000101010101010010101 0101010101001010101010010100111000011100 0001110100111000011100000111000001100010 1010101010010101010101010100101010101001 0100111000011100000111000001100010010101 0100101010101010101001010101010010100111 0000111000001110000011000101010101010010 1010101010101001010101010010100111000011 1000001110000011000101010101010010101010 1010101001010101010010100111000011100000 1110000011000101010101010010101010101010 “Life is of sequence”,1001010101010010100111000011100000111000 “Life is digital” 0110001010110000111000001110000011000101 0101010100101010101010101000101010101010 making sequencers and0101010101010001010101010100101010101010 supercomputers 1010010101010100101001110000111000001110 major tools for0001100010101100001110000011100000110001 genomics 0101010101001010101010101011100101100101 0101010101010101010100010111010100000000 0010111000000100010000010101010010101001 1001010101001001010010010100101010010010 Two Pillars of Genomics “Life is of sequence, Life is digital!” Revolutionizing life sciences No sequence, no knowledge! “All biology in the future will start with the knowledge of genomes and proceed hopefully. ” J. D. Watson, 2003 “未来所有生物学只有以基因组知识(重新）开始才有希望发展” An issue of cost! “One ‘buck’, one base” HGP $ 3.0 b/3 Gb ($1.0/1bp) 1999 $ 0.5 b/3 Gb 2005 $ 30 m/3 Gb ($ 0.01/bp) Future (1) $ 3.0 m /3 Gb (2) $ 0.1 m /3 Gb Sequencing is not a “luxurious” tool any longer Next-Generation Sequencers Aiming at “$100,000 genome” Sequencing Revolution 454 20 – 500 Mb (100-500 bp/read)/6 hours/run Sequencing Revolution Sequencing by Ligation SOLiD 3 Gb/run Sequencing Revolution Illumina Solexa 3-6 Gb/6 days ~1000 molecules per ~ 1 um cluster 100um ~1000 clusters per 100 um square Random array of ~40 million clusters per experiment clusters Next-Next-Generation Sequencers Aiming at “$1000 genome” NEXT-GEN SEQUENCING TECHNOLOGIES 26 (10):1146, Oct. 2008 PacBio to Start Selling Next-Gen Sequencer To Early Users in 2010 The company projects that with improvements to its enzyme biochemistry and in camera technology, it will eventually be able to generate more than 100 gigabases of sequence data per hour, provide reads at least as long as Sanger sequencing, and offer run times measuring in minutes at a cost of hundreds of dollars. Pacific Biosciences also prepares the 15-Minute Genome by 2013. GenomeWeb Newsroom February 13, 2008 VisiGen to Offer 'Nano-Sequencing' $1,000 Genome Service by 2009 [February 12, 2008] By Bernadette Toner. GenomeWeb News Editor SALT LAKE CITY (GenomeWeb News) – Next-generation sequencing firm VisiGen Biotechnologies plans to offer a service based on its real-time single- molecule sequencing, or "nano-sequencing machine", technology by the end of 2009, and to follow that with the launch of equipment and reagents in another 18 months to two years. The technology could enable researchers to sequence an entire human genome in less than a day for under $1,000, which can generate around 4 gigabases of data per day. At that throughput, the technology could sequence 44 human genomes per year at 10-fold coverage for around $1,000 per genome. In addition, read lengths for the instrument are expected to be around one kilobase. Oxford Nanopore Technologies • Earlier this year, UK-based Oxford Nanopore Technologies, a startup company developing a nanopore-based sequencing technology, raised £10 million ($20 million) in a second financing round from non-VC institutional and private investors, adding to an £7.5 million ($15 million) round in 2006 (see In Sequence 4/8/2008). Technical Platform of Genomics It is essential for developing countries to build powerful infrastructure for sustainable development of science ① Sequencing 104 MegaBACE 25 ABI 3700/3730 18 X Illumina Solexa I 1 X 454 2 X ABI SOLiD l “BGI to Ramp up Sequencing Abilities” NEW YORK March 26, 2008 (GenomeWeb News) – Beijing Genomics Institute is dramatically expanding its DNA sequencing capacity by adding fourteen new next-generation sequencers, … to bring BGI's raw-sequencing data output to up to 20 Gbps per day or more, ranking the 3rd biggest center in the world concerning its capacity. Space for 40 new sequencers Programers > 150 ② Bioinformatics Downing 3000 Supercomputers at BGI, Beijing & Hangzhou SGI Supercomputers in Beijing IBM Downing 2000 SUN CPUs: 1192 (Memory) (Storage) Memory: 2.3 T Storage: 1458 T Speed: 20T FLP Home-made new supercomputer at BGI-Shenzhen To read the genome BGI has contributed to most, if not all, programs for CNV detection and other applications by the next-generation sequencers, especially for Solexa. This is a revolution “This is just the start” 1. A world of crises and opportunities 2. Two pillars and platforms of genomics 3. “Three BY ALLs” for genomics 4. Four proposals for collaboration 5. Five collaborative projects undergoing An imbalanced world Two “tribes” in the world: The Rich & the Poor. Where is her hope? Kathmendu, Feb.11, 2008 Hope! Where is her hope? Kathmendu, Feb.11, 2008 The challenge is not only technology, but also humanity! Genomics Should not create more differences or to make the differences even bigger Nature April 27,2006 “Human genome sequencing