Changes

<div align="left"><span style="FONTfont-SIZEsize: 13.5pt;">Personal genomics, bioinformatics, and variomics</span><span style="FONTfont-SIZEsize: 9pt;">&nbsp;<br />

</span><strong><span style="FONTfont-SIZEsize: 9pt;">Jong Bhak¹, Ho Ghang¹, Rohit Reja¹,&nbsp;and Sangsoo Kim²*</span></strong><span style="FONTfont-SIZEsize: 9pt;"><br />

*Correspondence to: E-mail &nbsp;<a href="mailto:sskimb@ssu.ac.kr"><font color="#000080">sskimb@ssu.ac.kr</font></a> Tel +82-2-820-0457 Fax +82-2-824-4383 or E-mail </span><span style="FONT-SIZE: 9pt"><a href="mailto:jongbhak@yahoo.com"><font color="#0000ff">jongbhak@yahoo.com</font></a>&nbsp;Tel +82-42-879-8500 Fax +82-42-879-8519</span><span style="FONT-SIZE: 9pt"><br /></span><strong><span style="FONT-SIZE: 9pt"><br />Abstract</span></strong><span style="FONT-SIZE: 9pt"><br />There are at least five complete genome sequences available&nbsp;in 2008. It is known that there are over 15,000,000 genetic variants called SNPs in&nbsp;the dbSNP&nbsp;database. The cost of a full genome sequencing in 2009&nbsp;will be&nbsp;claimed to be less than $5000 USD.&nbsp;The genomics era has arrived in 2008. This review introduces&nbsp;technologies, bioinformatics,&nbsp;genomics visions, and variomics projects. Variomics is&nbsp;the&nbsp;study of the total genetic variation in an individual and&nbsp;populations.&nbsp;Research on&nbsp;genetic variation is the most&nbsp;valuable among many genomics research branches.&nbsp;Genomics and variomics projects will change biology and the society so dramatically that biology will become an everyday technology as personal computers and the internet. 'BioRevolution' is the term that can adequately describe this change.<br />

</span><span style="font-size: 9pt;"> </span><strong><span style="FONTfont-SIZEsize: 9pt;">Introduction<br /></span></strong><span style="FONTfont-SIZEsize: 9pt;"><strong>Abstract</strong><br />In 2008 at least five complete genome sequences are available. It is known that there are over 15,000,000 genetic variants, called SNPs, in the dbSNP database. The cost of full genome sequencing in 2009 is claimed to be less than $5000 USD. The genomics era has arrived in 2008. This review introduces technologies, bioinformatics, genomics visions, and variomics projects. Variomics is the study of the total genetic variation in an individual and populations. Research on genetic variation is the most valuable among many genomics research branches. Genomics and variomics projects will change biology and the society so dramatically that biology will become an everyday technology like personal computers and the internet. 'BioRevolution' is the term that can adequately describe this change.<br />&nbsp;<br /><strong>Introduction</strong><br />Since the launch of the Human Genome Project (HGP)&nbsp;in 1990 by NIH of USA, researchers have been developing faster DNA sequencers </span><span style="FONT-SIZE: 9pt">(ShendureChan, Mitra et al. 2004; Chan 2005; Metzker 2005; Gupta , 2008; Mardis , 2008; Metzker, 2005; Shendure et al., 2004)</span><span style="FONT-SIZE: 9pt">. HGP was has been said to be led by James Watson who modeled DNA in Cambridge, UK in 1953. In 2003, the International Human Genome Sequencing Consortium held a press conference to announce the completion of the human genome </span><span style="FONT-SIZE: 9pt">(IHGSC , 2004)</span><span style="FONT-SIZE: 9pt">. In 2008, after 55 years, his Watson's complete genome sequence was publicized by using 454 DNA sequencers developed by a company </span><span style="FONT-SIZE: 9pt">rather than a research institute (Wheeler, Srinivasan et al. , 2008)</span><span style="FONT-SIZE: 9pt">.&nbsp;In 2007, Craig Venter of , a former Celera founder , published his own personal genome in PLoS Biology </span><span style="FONT-SIZE: 9pt">(Levy, Sutton et al. , 2007)</span><span style="FONT-SIZE: 9pt">.&nbsp;We are entering the personalized biology era with the advent of next generation sequencing technologies.<br />

</span><strong><span style="FONT-SIZE: 9pt">DNA sequencing</span></strong><span style="FONT-SIZE: 9pt"><br />The first breakthrough in genome sequencing came from Watson's&nbsp;colleague , Fred Sanger, in Cambridge, Fred SangerUK. In 1977, Sanger and his team produced the first useful DNA sequencing method and publicized the first complete genome </span><span style="FONT-SIZE: 9pt">(Sanger, Air et al. , 1977)</span><span style="FONT-SIZE: 9pt">. It was a tiny virus genome known as phi X 174. Soon after phi X 174, he published the first complete organelle genome which was a mitochondrion </span><span style="FONT-SIZE: 9pt">(Anderson, Bankier et al. , 1981)</span><span style="FONT-SIZE: 9pt">. By 1998, researchers in the US evaluated multiplex genome sequencing technologies and were aware that one person's whole genome could be sequenced in one a day using contemporary technologies. George Church was the a Ph.D. student of Walter Gilbert who received a Nobel Prize with Sanger for developing a sequencing method. Gilbert's method was not widely used much. However, his colleague Church kept developing continued to develop sequencing methods. One of them is based on the Polony idea </span><span style="FONT-SIZE: 9pt">(Porreca, Shendure et al. , 2006)</span><span style="FONT-SIZE: 9pt">. This technology is used by KNOME Inc. that is , a full genome sequencing company. Along with KNOME, other companies , such as Complete Genomics , are now producing DNA sequences cheaply and in an unprecedented capacity. The speed of sequencing is advancing many folds per year, much faster than the cycle of semiconductor chips in computer industries. Also, genome sequencing technology&nbsp;is becoming an everyday technology&nbsp;to at the level as computer CPUs are universally used. In five years of ' time, experts predict that everyone in developed nations will be able to have his or her own genome information if he/she wanted it. Due to its far reaching consequences in medicine, health, biology, nanotechnology, and information technology, DNA sequencing&nbsp;will become&nbsp;the most important industrial technology ever developed in during the next decades.&nbsp;<br />

</span><strong><span style="FONT-SIZE: 9pt">Personal Genomics</span></strong><span style="FONT-SIZE: 9pt"><br />In 2009, genome sequencing technologies will achieve one person's whole genome per day in terms of DNA fragments sequenced. Personal genomics is a new term that utilizes such fast sequencers. In 2008, the cost for one personal genome is less than $350,000 USD. If the cost goes down below $1,000 USD, the impact of personal genomics is predicted to be the largest ever in biology&nbsp;on in common people's lifelives.&nbsp;Reflecting this technological advancement to the society is the PGP (Personal Genome Project), a project to sequence as many people as possible with lowest possible&nbsp;costs </span><span style="FONT-SIZE: 9pt">cost (Church , 2005)</span><span style="FONT-SIZE: 9pt">. At present, Google , Inc. and the Church group are working together to sequence 100,000 people's genetic regions of DNA. In Saudi Arabia, the government is planning to sequence 100 Arabic people's genome. In Europe, there are various groups of people and nations who have been genotyping the those populations. Especially, Iceland has been especially successful in that effort by utilizing their well-kept genealogical data encompassing 100,000s hundreds of thousands of people. In Asia, Jeongsun Seo of Seoul National University has been working on the East Asia Genome Project in during the past several years. His group has collected thousands of samples from Mongolian tribes with a gigantic extremely large genealogical tree among them </span><span style="FONT-SIZE: 9pt">(Park et al. , 2008; Sung et al. , 2008)</span><span style="FONT-SIZE: 9pt">. Seo is said to&nbsp;be sequencing at least 100 Korean genomes in collaboration with Church and Green Cross , Inc. of Korea. The aim of Seo's genome project is to produce a resource for the East Asians as well as Koreans. He is presently sequencing at least two Korean people. In China, Beijing Genome Institute has been successful in terms of sequencing. Their first achievement came from a plant genome, rice. After rice, they launched a 100 Han Chinese genome sequencing project. In Nov. 2008, they published their first Chinese genome in a jouraljournal, Nature. In Dec. 2008, another Korean group, Lee Gilyeo Cancer and Diabetes Institute (LCDI)&nbsp;and Korean Bioinformation Center (KOBIC) made a Korean genome sequence public. The genome was sequenced by Solexa paired-end sequencer , and comparative genomics analyses and SNP data were uploaded as a public resource for everyone.&nbsp;The time taken It took only one week to analyze the 7.8x Korean genome took only one week using 150 computer CPUs to produce mapping DNA fragments to a reference genome, generate new SNP information, compare that with other individual genomes, and map it with 1600 already known phehotype phenotype information from the public literature.<br />&nbsp;<br /><strong>Genome Revolution </strong><br />These public genome data alongside previously known Craig Venter's and James Watson's mark that full genome sequences are not soley in academic domain anymore. Anyone who has money and the will can sequence human genomes. This 'genomic revolution' will eventually lead to the 'BioRevolution' in terms of making the most essential human information completely mapped and publically available. This is revolutionary, because humans can now engineer themselves with a map or a blue print not directly relying on trial and error style conventional evolutionary methods. This indicates that evolution has moved to a conscious level driving evolution. We are in effect designing evolution using computers. &nbsp;<br />

</span><strong><span style="FONT-SIZE: 9pt">Genome Revolution&nbsp;Genomes and Personalized Medicine</span></strong><strong><span style="FONT-SIZE: 9pt"><br /></span></strong><span style="FONT-SIZE: 9pt">These public genome data alongside previously known Craig VenterThe consequences of 's and James Watson's mark that full genome sequences are not in academic domain anymore. Anyone who has money and will can sequence human genomes. This BioRevolution'where genomic revolution' will eventually lead information is utilized by scientists to the 'BioRevolution' in terms engineers all kinds of making the most essential human information completely mapped and publically availablebiological processes, including evolution itself, will bring us personalized medicine. These are revolutionary because humans can now engineer themselves with a map or a blue print not directly relying on trial The essence of personalized medicine is that enzymes in our tissues, such as cytochrome P450, have distinct differences among individuals and error style conventional evolutionary methodspopulations. This indicates that evolution went into a conscious level of driving evolution. It is almost designing the evolution using computersCertain drugs produce different responses in individuals.&nbsp;<br />

</spanstrong>Cytochrome p450 family example</strong><span style="FONT-SIZE: 9pt"br />Genomes The cytochrome P450 (CYP) family of liver enzymes is responsible for breaking down more than 30 different classes of drugs during Phase I of drug metabolism. Structural and Personalized MedicineSNP variations of the genes that code for these enzymes can influence their ability to metabolize certain drugs. Based upon this, a population can be categorized into four major types of drug metabolizers: <br /span>&quot;&nbsp;&nbsp; &nbsp;Extensive metabolizers: Individuals that can be administered with normal drug dosage <br /strong><span style="FONT-SIZE&quot;&nbsp;&nbsp; &nbsp;Intermediate metabolizers: 9pt">Individuals that metabolize drugs with a&nbsp; slower than normal rate. <br />The consequences of 'BioRevolution' where genomic information is utilized by scientists to engineers all kinds of biological processes including evolution itself will bring us the personalized medicine&quot;&nbsp;&nbsp; &nbsp;Poor metabolizers: Individuals with poor metabolizing rates. The essence of personalized medicine is that enzymes in our tissues such as cytochrome P450 have distinct differences among individuals Drugs may accumulate and populations. Certain drugs produce different responses in individualscause serious adverse effects.<br />&quot;&nbsp;&nbsp; &nbsp;Ultra metabolizers: Individuals with metabolizing rates even faster than extensive metabolizers. They may experience no effect of drug activity. <br />

</span><strong><span style="FONT-SIZE: 9pt">Cytochrome p450 family example</span></strong><span style="FONT-SIZE: 9pt"><br />The cytochrome P450 (CYP) family of liver enzymesIn early 2005, the US FDA cleared the AmpliChip&nbspreg;are responsible for breaking down more than 30 different classes of drugs during phase I of drug metabolism. Structural and SNP CYP450 Test, which measures variations in two genes of the&nbsp;genes that code for these enzymes can influence their ability CYP450 enzyme system: CYP2D6 and CYP2C19. The Roche AmpliChip CYP450 Test is intended to metabolize certain drugs. Based upon this, identify a population can be categorized into four major types of drug metabolizers: </span></div><div align="left"><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">(</font><patient's CYP2D6 and CYP2C19 genotype from genomic DNA extracted from a href="http://wwwwhole blood sample.macrogen.co.kr/eng/macrogen/stateInformation about CYP2D6 and CYP2C19 genotype may be used as an aid to clinicians in determining therapeutic strategy and treatment dose for therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene product.jsp"><font color="#0000ff" size="2">http://www.macrogen.co.kr/eng/macrogen/state.jsp</font><br /a><font size="2">)</font></div></div><ul type="disc"> <li style="TEXT-ALIGN: left"><span style="FONT-SIZE: 9pt">Extensive metabolizers: The&nbsp;individuals that can be administered with normal drug dosage </span></li> <li style="TEXT-ALIGN: left"><span style="FONT-SIZE: 9pt">Intermediate metabolizers&nbsp;: The individuals that metabolizes drug with a rate slower than the normal rate. </span></li> <li style="TEXT-ALIGN: left"><span style="FONT-SIZE: 9pt">Poor metabolizers: The individuals with poor metabolizing rate. Drugs make accumulate and cause serious adverse effects. </span></li> <li style="TEXT-ALIGN: left"><span style="FONT-SIZE: 9pt">Ultra metabolizers: Individuals with metabolizing rate faster than extensive metabolizers. They may experience no effect of drug activity. </span></li></ul><div align="left"><span style="FONT-SIZE: 9pt"><br /></span><strong><span style="FONT-SIZE: 9pt">Variomics</span></strong><span style="FONT-SIZE: 9pt"><br />The most important scientific data out of personal genomes are the precise sequence differences among individuals. Such differences have many types.&nbsp;There are structural differences between among chromosomes. There can be insertions and deletions of DNA segments. There are certain fragments that appear as repeats in genomes. Mapping all these structural genetic variations can be briefly termed as 'variomics'. A variome is the totality of genetic variation found in an individual, a population, and a species. Among all the variations we know,&nbsp;the most common one is the single nucleotide polymorphisms (SNP).&nbsp;In Korea, mapping the variome has been pursued relatively early , and there are several groups who are mapping the genetic variations. KOBIC has several very early stage, if not the earliest in the world, variome servers; <a href="http://variome.net/"><font color="#800080">http://variome.net</font></a> and <a href="http://variomics.net/"><font color="#0000ff">http://variomics.net</font></a>. Along with SNP variation, the copy number variation (CNV) is also important. Some recent reports tell us that CNVs can be as variable as or even more variable than SNPs that are simple DNA base changes in populations. Yeun-Jun Chung of the Catholic University of Korea has been mapping CNVs among Korean people (Kim et al. , 2008).<br /span><br /div><div align="left"strong>Human Variome Project (HVP)<span style="FONT-SIZE: 9pt"/strong>In early 2005, the US FDA cleared the AmpliChip<sup>&reg;<br /sup> CYP450 TestAs an international collaboration, headed by Richard Cotton, which measures variations HVP was launched in two genes of the CYP450 enzyme system2006 (http: CYP2D6 //humanvariomeproject.org) (Ring et al., 2006). HVP aims to make clinicians who have been working on rare diseases, to work together with molecular biologists and CYP2C19bioinformaticians. The Roche AmpliChip CYP450 Test Their goal is intended to identify a patient's CYP2D6 and CYP2C19 link medical information with genotype from genomic DNA extracted from a whole blood sampleinformation. Information about CYP2D6 and CYP2C19 Succinctly, this process is called genotype may to phenotype mapping. As several full human genome sequences are already available, mapping phenotypes to full genomes will be used as an aid to clinicians the major challenge of biology in determining therapeutic strategy and treatment dose for therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene productnext 20 years.<br />

</span></div><div align="left"><strong><span style="FONT-SIZE: 9pt">Human Asian Variome Project (HVPAVP)</span></strong><br /div><p><span style="FONTAlongside and with the associations of eIMBL, A-SIZE: 9pt">As an international collaborationIMBN, headed by Richard Cottonand HVP, HVP a variome project that is working to map the Asian population variome was launched in 2006 2008. This was a group effort by Korean researchers who have been interested in genome sequences, SNPs, and CNVs. They have formed the KOrean VAriome Consortium (<a href="httpKOVAC://humanvariomeproject.org/"><font color="#0000ff">http://humanvariomeprojectvariome.org</font></a>kr) </span><span style="FONT-SIZE: 9pt">(Ringand support AVP as one of the first projects. eIMBL, the virtual laboratory network of Asia linking key biology groups modeled after EMBL, Kwok et al. 2006)</span><span style="FONT-SIZE: 9pt">. HVP aims to&nbsp;make clinicians who have been working on rare diseaseshas acquired $80, 000 USD in 2008 to work together with molecular biologists and bioinformaticianssupport AVP. Their goal is to link medical information with genotype information. Succinctly this process is called genotype to phenotype mapping. As several full human genome sequences are already available, mapping phenotypes eIMBL aims to establish a virtual bioinformatics center in the full genomes Asia Pacific region that will be the major challenge of biology link many bioinformation processing scientists in the next 20 yearsAsia.&nbsp;<br />

</span><strong><span style="FONT-SIZE: 9pt">Asian Variome Project (AVP)</span>Construction of Reference Genomes for the world</strong><span style="FONT-SIZE: 9pt"><br />Alongside Sanger Center, EBI, NCBI, and with the associations University of eIMBL, A-IMBN, and HVP, Washington Genome Center have formed a variome project that tries consortium to map Asian population variome was launched in 2008. This was produce a group effort of Korean researchers who have been interested in reference genome sequences,&nbsp;SNPs, and CNVs. They have formed a Korean Variome Consortium (KOVAC: <a href="http://variomereferencegenome.kr/"><font color="#0000ff">http://variomeorg).kr</font></a>) and supported AVP as one of A reference standard is the most important standard among all the standards. Providing an accurate reference genome to biologists is an important task. The first projectsreference genome by the above consortium is based on Caucasian genomes. eIMBL that is Due to the virtual laboratory network extent of Asia linking key biology SNPs and CNVs, it is necessary to construct reference genomes for diverse ethnic groups modeled after EMBL has acquired $80. In Korea, since 2006,000 USD the reference standard genome project began and produced the first draft for Koreans in November, 2008 , using a male donor. Through the bioinformatic analysis, the Korean researchers in LCDI and KOBIC found that there was a good justification for any nation to launch large scale genome projects to support AVPmap population diversities. eIMBL aims to establish Even such close populations as Korean and the Chinese showed a virtual bioinformatics center in Asia Pacific region that links many bioinformation processing scientists in Asialarge quantity of SNP differences.<br />

<span style="FONT-SIZE: 9pt"><strong>Construction of Reference Bioinformatics for Personal Genomes for the world.<br />and Variomes</strong><br /span><span style="FONT-SIZE: 9pt">Sanger center, EBI, NCBI and Bioinformatics is the key in personal genome center of the University projects and variome projects. Bioinformatics is not merely a set of Washington have formed a consortium to produce tools but a reference genome (<a href="http://referencegenome.org/"><font color="#000080">http://referencegenomescientific discipline.org</font></It regards life as a>). Reference standard is gigantic information processing phenomenon and works to map its components and to model the most important standard among all emerging networks of the standardscomponents.&nbsp;Providing an accurate reference genome to biologists Bioinformatics in 2008 is driving biology into an important taskinformation science. The first reference genome Most biology research projects produce massive amounts of data that cannot be processed by the above consortium is based on Caucasian genomeshand. Due to Nearly all biological research outcomes in the extent next five years will have some form of high throughput data such as genome sequences, microarray data, proteome analyses, SNPs and CNVs, it is necessary to construct reference genomes for diverse ethnic groups. In Korea, since 2006epigenome chips, the reference standard genome project has begun and produced the first draft for Koreans in Novlarge scale phenotype mapping. 2008 using a male doner. Through the analysis, the Korean researchers Bioinformatics tools in LDCI genomics and KOBIC variomics can be found that there is a strong justification for any nation to launch large scale genome projects to map population diversitiesfrom various internet resources. Even There are several bioinformatics hubs such&nbsp;close populationsas NCBI (National Center for Biotechnology Information), EBI (European Bioinformatics Institute), DDBJ (Databank of Japan), the&nbsp;Korean and&nbsp;the ChineseKOBIC. Some others are: Bioinformatics Organization (http://Bioinformatics.Org), seemed to show a large quantity of SNP differenceEMBnet (http://www.embnet.<org/), and The International Society for Computational Biology (http://span>iscb.org). <br />

</span><strong><span style="FONT-SIZE: 9pt">Bioinformatics for Personal Genomes and Variomes</span></strong><span style="FONT-SIZE: 9pt"><br />Bioinformatics is the key in personal genome projects and variome projects. Bioinformatics is not a set of tools but it is a proper scientific discipline. It regards life as a gigantic information processing phenomenon and tries to map its components and to model the emerging networks of the components. Bioinformatics in 2008 is driving biology into an information science. Most biology researches are now with massive amount of data that cannot be processed by hand. Nearly all the biological research outcomes in the next&nbsp;five years will have some form of high throughput data such as genome sequences, microarray data, proteome analyses, SNPs, epigenome chips, and large scale phenotype mapping. Bioinformatics tools in genomics and variomics can be found from various internet resources. There are various bioinformatics hubs such as NCBI (National Center for Biotechnology Information), EBI (European Bioinformatics Institute), DDBJ (Databank of Japan), and KOBIC.&nbsp;Some&nbsp;others are: Bioinformatics Organization (<a href="http://bioinformatics.org/"><font color="#0000ff">http://Bioinformatics.Org</font></a>), EMBnet (<a href="http://www.embnet.org/"><font color="#0000ff">http://www.embnet.org/</font></a>), and&nbsp;The International Society for Computational Biology (<a href="http://iscb.org/"><font color="#0000ff">http://iscb.org</font></a>). The following are major bioinformatics journals:<br />

</span></p><ul type="disc"> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Algorithms in <span style="FONT-SIZE: 9pt">Molecular Biology (http://www.almob.org/) </span></span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Bioinformatics (http://bioinformatics.oxfordjournals.org/) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">BMC Bioinformatics (http://www.biomedcentral.com/bmcbioinformatics) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Briefings in Bioinformatics (http://bib.oxfordjournals.org/) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Genome Research&nbsp;(http://genome.cshlp.org/) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Genomics and Informatics (<a href="http://www.genominfo.org/"><font color="#0000ff">http://www.genominfo.org</font></a>) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">The International Journal of Biostatistics (http://www.bepress.com/ijb/) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Journal of Computational Biology (http://www.liebertpub.com/Products/Product.aspx?pid=31&amp;AspxAutoDetectCookieSupport=1) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Cancer Informatics (http://www.la-press.com/journal.php?pa=description&amp;journal_id=10) </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">Molecular Systems Biology (http://www.nature.com/msb/index.html </span></li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">PLoS Computational Biology (<a href="http://www.ploscompbiol.org/home.action">http://www.ploscompbiol.org/home.action</a>)</span> </li> <li style="TEXT-ALIGN: left"><span style="FONTfont-SIZEsize: 9pt;">International Journal of Bioinformatics Research and Applications (http://www.inderscience.com/browse/index.php?journalcode=ijbra)</span> </li>

<strong><span style="FONT-SIZE: 9pt">Sequencing Mapping Expression using DNA, Metagenomics, and Ecogenomics</span>sequencing</strong><span style="FONT-SIZE: 9pt"><br />Next generation DNA sequencing methods are not only technologies were mostly used for mapping genomesgenotypes. They can be However, they are now used to map the environmentRNA expression levels in cells. Cells produce various types of RNA. It mRNA is called ecogenomicsthe most abundant and important. Environment to humans can be various microbial, plantIn the past, microarray and animal interactions around us. Especially, microbial interaction is critical DNA chips were used to our healthmeasure expression levels. Gut bacteria They are natural environment to usnot accurate and take many bioinformatic adjustments before producing reliable expression data. New sequencing technologies can measure expression levels much more accurately. Metagenomics is a methodology that sequences By sequencing the whole set of microbes in our food tract. Researchers are realizing that human genome is complemented by such environmental genomes. A new termRNAs, 'ecogenomics' is we can now used to describe these conceptsquantify the expression levels by precisely knowing the RNA sequences. Metagenomics and ecogenomics are for mapping Sequencing technologies will restructure the expression analyses in the variation of environmental genetic factorsfuture.<br />

</span><strong><span style="FONT-SIZE: 9pt">Mapping expression using DNA sequencing</span></strong><span style="FONTThe following are on-SIZE: 9pt"><br />DNA sequencing technology&nbsp;used to be&nbsp;for mapping genotypes. However, they are now used to map expression levels in cellsline genomics sites. Cells produce various RNAs. mRNA is the most abundant and important. In the past, microarray and DNA chips were used for measuring expression levels. They are not accurate and it takes many bioinformatic adjustments before it becomes reliable expression data. New sequencing technologies can measure expression levels much more accurately. By sequencing the RNAs, we can now quantify the mRNA levels by precisely knowing the RNA sequences. Sequencing technologies will restructure the expression analyses in the future.</span>&nbsp;<br /><span style="FONT-SIZE: 9pt"><br />

<strong/span><ul> <li>Linking Genome information On<span style="font-linesize: 9pt;">Genomics portal: http://genomics.org</strongspan><br /li>Sequencing a genome is one thing but analyzing the whole genome is another thing <li><span style="font-size: 9pt;">Personal Genome Project: http://personalgenomes. Therefore, a worldwide effort is required to link all the genome information for proper management and utilizationorg</span></li> <li><span style="font-size: 9pt;">openfree Genomics Project: http://personalgenome. The internet is the best infrastructure for genome information exchangenet</span></li> <li><span style="font-size: 9pt;">Personal Genome sequencing company: http://www. Bioinformatics resources should be available as freely as possible for underdeveloped and developing nationsknome. com</span></li> <li><span style="font-size: 9pt;">Personal Genome sequencing and associated analysese should be done freely in certain instances by the support of local governments and international organizationsSNP typing: http://decodeme. For maximum efficient, an adequote data and information license is also requiredcom</span></li> <li><span style="font-size: 9pt;">Google's Personal Genome Typing: http://23andme. Some researchers propose an openfree sharing of bioinformatics analysis tools as&nbspcom</span></li> <li><span style="font-size: 9pt;well as the genome sequences (under proper permission)">The Sanger Centre: http://sanger.ac.&nbsp;One of such as movement is Free Genomics (uk</span></li> <li><a hrefspan style="font-size: 9pt;">General Omics site: http://freegenomicsomics.org</span></li> <li><span style="font-size: 9pt;">Korean Genome Data Site: http://freegenomicskoreagenome.org</aspan></li> <li><span style="font-size: 9pt;">)Korean Bioinformation Center: http://kobic.&nbspkr</span></li></ul><span style="font-size: 9pt;"><br /><strong>Conclusion</strong><br />We have examined the current trends in genomics and variomics. In 2009 and onwards, personal genome projects will produce an unprecedented amount of biological data. New bioinformatics technologies will be required to handle them. New sequencing technologies will drive the next decades of biology and transform medical practices. Fast sequencing brought us interesting and unexpected applications such as metagenomics and ecogenomics. <br />

<strong>Acknowledgements </spanstrong><divbr />SK was supported by Soongsil University Research Fund. JB, GH, and RR were supported by KRIBB/KOBIC fund from the MEST of Korea. The authors thank Maryana Bhak for editing the manuscript.<font size="2"br /><br /><strong>ConclusionReferences</strong><br /font>Anderson, S., A. T. Bankier, B. G. Barrell, M. H. de Bruijn, A. R. Coulson, J. Drouin, I. C. Eperon, D. P. Nierlich, B. A. Roe, F. Sanger, P. H. Schreier, A. J. Smith, R. Staden, and I. G. Young. (1981). Sequence and organization of the human mitochondrial genome. Nature 290:457-65.<br />Chan, E. Y. (2005). Advances in sequencing technology. Mutat Res 573:13-40.<font size="2"br />In 2009 and onwardsChurch, G. M. (2005). The personal genome projects will produce unprecedented amount of biological dataproject. Mol Syst Biol 1:2005 0030.<br />Gupta, P. K. New bioinformatics technologies will be required to handle them(2008). New Single-molecule DNA sequencing technologies will drive for future genomics research. Trends Biotechnol 26:602-11.<br />IHGSC. (2004). Finishing the next decades euchromatic sequence of biology and transform the medical practices in hospitalshuman genome. Fast sequencing unexpectedly brought us interesting applications such as metagenomics and ecogenomicsNature 431:931-45. <br /font><font size="2">We have examined Kim, T.-M., S.-H. Yim, and Y. Chung. (2008). Copy Number Variations in the current trends in genomics Human Genome: Potential Source for Individual Diversity and variomicsDisease Association Studies. Genomics &amp; Informatics 6(1):1-7. <br /font>Levy, S., G. Sutton, P. C. Ng, L. Feuk, A. L. Halpern, B. P. Walenz, N. Axelrod, J. Huang, E. F. Kirkness, G. Denisov, Y. Lin, J. R. MacDonald, A. W. Pang, M. Shago, T. B. Stockwell, A. Tsiamouri, V. Bafna, V. Bansal, S. A. Kravitz, D. A. Busam, K. Y. Beeson, T. C. McIntosh, K. A. Remington, J. F. Abril, J. Gill, J. Borman, Y. H. Rogers, M. E. Frazier, S. W. Scherer, R. L. Strausberg, and J. C. Venter. (2007). The diploid genome sequence of an individual human. PLoS Biol 5:e254.<br />Mardis, E. R. (2008). The impact of next-generation sequencing technology on genetics. Trends Genet 24:133-41.<br /div>Metzker, M. L. (2005). Emerging technologies in DNA sequencing. Genome Res 15:1767-76.<divbr />Park, H., K. J-H., S.-I. Cho, J. Sung, H.-L. Kim, Y. S. Ju, G. Bayasgalan, M.-K. Lee, and J.-S. Seo. (2008). Genome-wide Linkage Study for Plasma HDL Cholesterol Level in an Isolated Population of Mongolia. Genomics &amp; Informatics 6(1):8-13.<strongbr />Porreca, G. J., J. Shendure, and G. M. Church. (2006). Polony DNA sequencing. Curr Protoc Mol Biol Chapter 7:Unit 7 8.<font size="2"br />AcknowledgementsRing, H. Z., P. Y. Kwok, and R. G. Cotton. (2006). Human Variome Project: an international collaboration to catalogue human genetic variation. Pharmacogenomics 7:969-72.<br /font>Sanger, F., G. M. Air, B. G. Barrell, N. L. Brown, A. R. Coulson, C. A. Fiddes, C. A. Hutchison, P. M. Slocombe, and M. Smith. (1977). Nucleotide sequence of bacteriophage phi X174 DNA. Nature 265:687-95.<br /strong>Shendure, J., R. D. Mitra, C. Varma, and G. M. Church. (2004). Advanced sequencing technologies: methods and goals. Nat Rev Genet 5:335-44.<br />Sung, J., M. K. Lee, and J.-S. Seo. (2008). Inbreeding Coefficients in Two Isolated Mongolian Populations - GENDISCAN Study. Genomics &amp; Informatics 6(1).<font size="2"br />SK was supported Wheeler, D. A., M. Srinivasan, M. Egholm, Y. Shen, L. Chen, A. McGuire, W. He, Y. J. Chen, V. Makhijani, G. T. Roth, X. Gomes, K. Tartaro, F. Niazi, C. L. Turcotte, G. P. Irzyk, J. R. Lupski, C. Chinault, X. Z. Song, Y. Liu, Y. Yuan, L. Nazareth, X. Qin, D. M. Muzny, M. Margulies, G. M. Weinstock, R. A. Gibbs, and J. M. Rothberg. (2008). The complete genome of an individual by Soongsil University Reserach Fundmassively parallel DNA sequencing. Nature 452:872-6. </font><br />

</div><div><font size="2"><strongspan>References</strong></font></div><div span style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">IHGSC (2004). Finishing the euchromatic sequence of the human genome. <em>Nature</em> 431(7011), 931-45.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Anderson, S., A. T. Bankier, <em>et al.</em> (1981). Sequence and organization of the human mitochondrial genome. <em>Nature</em> 290(5806), 457-65.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt9pt; TEXT-INDENT: -36pt"><font size="2">Chan, E. Y. (2005). Advances in sequencing technology. <em>Mutat. Res.<br /em> 573(1-2), 13-40.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Church, G. M. (2005). The personal genome project. <em>Mol. Syst. Biol.</em> 1<strongspan>,</strong> 2005.0030.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Gupta, P. K. (2008). Single-molecule DNA sequencing technologies for future genomics research. <em>Trends Biotechnol.</em> 26(11), 602-11.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Kim, T-M. <em>et al.</em> (2008). Copy Number Variations in the Human Genome: Potential Source for Individual Diversity and Disease Association Studies. <em>Genomics &amp; Informatics</em>&nbsp;6(1), 1-7.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Levy, S., G. Sutton, <em>et al</em>. (2007). The diploid genome sequence of an individual human. <em>PLoS Biol.</em> 5(10), e254.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Mardis, E. R. (2008). The impact of next-generation sequencing technology on genetics. <em>Trends Genet.</em> 24(3), 133-41.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Metzker, M. L. (2005). Emerging technologies in DNA sequencing. <em>Genome Res.</em> 15(12), 1767-76.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Park, H. <em>et al</em>. (2008). Genome-wide Linkage Study for Plasma HDL Cholesterol Level in an Isolated Population of Mongolia. <em>Genomics &amp; Informatics</em> 6(1), 8-13.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Porreca, G. J., J. Shendure, <em>et al</em>. (2006). Polony DNA sequencing. <em>Curr. Prot. Mol. Biol.</em> Chapter 7: Unit 7 8.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Ring, H. Z., P. Y. Kwok, <em>et al</em>. (2006). Human Variome Project: an international collaboration to catalogue human genetic variation. <em>Pharmacogenomics</em> 7(7), 969-72.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Sanger, F., G. M. Air, <em>et al</em>. (1977). Nucleotide sequence of bacteriophage phi X174 DNA. <em>Nature</em> 265(5596), 687-95.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Shendure, J., R. D. Mitra, <em>et al</em>. (2004). Advanced sequencing technologies: methods and goals. <em>Nat.</em> <em>Rev. Genet.</em> 5(5), 335-44.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Sung, J. et al. (2008). Inbreeding Coefficients in Two Isolated Mongolian Populations - GENDISCAN Study. <em>Genomics &amp; Informatics</em> 6(1): 14-17.</font></div><div style="MARGIN: 0cm 0cm 0pt 36pt; TEXT-INDENT: -36pt"><font size="2">Wheeler, D. A., M. Srinivasan, <em>et al</em>. (2008). The complete genome of an individual by massively parallel DNA sequencing. <em>Nature</em> 452(7189), 872-6.</font></div><p>&nbsp;</p>