8e73439c3de6d6560d50b267be0ba4016cc40f86 jnavarr5 Mon Aug 19 14:43:06 2019 -0700 Adding a Table of Contents for the history page, refs #20314 diff --git src/hg/htdocs/goldenPath/history.html src/hg/htdocs/goldenPath/history.html index a09de2b..c3d2803 100755 --- src/hg/htdocs/goldenPath/history.html +++ src/hg/htdocs/goldenPath/history.html @@ -1,24 +1,44 @@ <!DOCTYPE html> <!--#set var="TITLE" value="Genome Browser History" --> <!--#set var="ROOT" value=".." --> <!-- Relative paths to support mirror sites with non-standard GB docs install --> <!--#include virtual="$ROOT/inc/gbPageStart.html" --> <h1>UCSC Genome Browser Project History</h1> +<h2>Table of Contents</h2> +<ul> + <li><a href="#overview">Genome Browser overview</a></li> + <li><a href="#race">Human Genome Project Race</a></li> + <ul class="gbsNoBullet"> + <li><a href="#celera">New challenger, Celera Genomics</a></li> + <li><a href="#push">Push to the Finish Line</a></li> + </ul> + <li><a href="#ENCODE">The ENCODE Project</a></li> + <ul class="gbsNoBullet"> + <li><a href="#ucsc">UC Santa Cruz's role</a></li> + </ul> + <li><a href="#primer">UCSC Genome Research Primer</a></li> + <ul class="gbsNoBullet"> + <li><a href="#comparative">Comparative Genomics</a></li> + <li><a href="#health">Possibilities for Health</a></li> + </ul> +</ul> + +<a name="overview"></a> <h2>Genome Browser overview</h2> <p> The UCSC Genome Browser is a web-based tool serving as a multi-powered microscope that allows researchers to view all 23 chromosomes of the human genome at any scale from a full chromosome down to an individual nucleotide. The browser integrates the work of countless scientists in laboratories worldwide, including work generated at UCSC, in an interactive, graphical display.</p> <p> Zoomed out, the coarse-level view shows early chromosome maps as determined by electron microscopy, then the browser drills down to levels of increasing detail, focusing first on chromosome bands, then on gene clusters (showing known genes-mostly those linked to diseases), then single genes, then the components of genes, and finally on the nucleotides-the As, Cs, Gs, and Ts that make up the genome alphabet. Not only does the browser show the genome sequence, but it also delineates known areas of the genome and offers supplementary information about the genes-in effect, providing the word breaks and punctuation.</p> <p> @@ -68,82 +88,86 @@ critical step toward fully understanding the workings of the human genome, a project that will occupy science and medicine for many years. The browser platform has multiple potential uses that can improve diagnosis, prevention, and cures for disease. The usefulness of the UCSC Genome Browser lead to spin-offs, or genome browser mirrors, such as the following:</p> <ul> <li><a href="https://news.ucsc.edu/2008/05/2242.html" target="_blank">The HIV Data Browser</a></li> <li><a href="https://xena.ucsc.edu/welcome-to-ucsc-xena/" target="_blank">The UCSC Cancer Genomics Browser</a></li> <li><a href="https://genome.ucsc.edu/encode/" target="_blank">The data collection center for the international ENCODE project</a></li> <li><a href="http://genome.ucsc.edu/ebolaPortal/" target="_blank">The UCSC Ebola Virus Genome Browser</a></li> </ul> +<a name="race"></a> <h2>Human Genome Project Race</h2> <p> In December 1999, the International Human Genome Project (IHGP) came to UC Santa Cruz when Eric Lander, the director of the Whitehead sequencing center (Whitehead Institute/MIT Center for Genome Research), invited David Haussler to help annotate the human genome. In particular, Lander wanted help in discovering the locations of the genes, which make up only approximately 1.5% of the sequence. Haussler had previously applied a mathematical technique known as hidden Markov models (HMMs) to the task of computer gene-finding. This application of HMMs had quickly become the dominant gene-finding methodology and was used successfully on the <i>Drosophila melanogaster</i> (fruit fly) genome.</p> <p> At the time UCSC entered the International Human Genome Project (IHGP), the IHGP was assembling the sequence one piece (or, in the jargon of molecular biology, one "clone") at a time, and intending to string the pieces together based on a precisely constructed clone map. This approach had been shown to work very well with <i>Caenorhabditis elegans</i> (a roundworm) and human chromosome 22. But the process of making sure every last part of the sequence is read and put together properly is quite labor-intensive.</p> <p> Haussler enlisted Jim Kent, then a graduate student at UCSC's Department of Molecular, Cell, & Developmental Biology, along with systems engineer Patrick Gavin, and graduate students Terrence Furey and David Kulp (who had led the gene-finding effort on the Drosophila genome). This was the birth of the UCSC Genome Browser Group.</p> -<h3>New challenger, Celera</h3> +<a name="celera"></a> +<h3>New challenger, Celera Genomics</h3> <p> It was a crucial time for the international project. A private company, Celera Genomics, had announced its intention to assemble the human genome sequence well in advance of the public effort, raising the fear that the sequence would be protected by patents and thus not be freely available to scientists. Celera Genomics was using an alternative approach, a so-called whole genome "shotgun," where small bits of the sequence are read at random from the genome, and then a computer program assembles these bits into an approximation of the genome as a whole. By using this approach, Celera's assembly would still have numerous gaps and ambiguities, but the entire project from start to finish could be done in less than half the time the IHGP planned for their effort.</p> <p> An approach resulting in numerous gaps and ambiguities was necessary if the IHGP's draft sequence was to have similar utility to Celera's sequence, and in particular to prevent Celera and its clients from locking up significant portions of the human genome under patents. A number of groups within the IHGP were working on the second stage of assembly that would merge the approximately 400,000 contigs into larger pieces and order them along the human chromosomes so that research groups could find the human genes. However, the process was slow and arduous. Even with the outstanding mapping information provided by Bob Waterston's group at Washington University, the second stage assembly turned out to be like an extremely difficult jigsaw puzzle, with many layers of conflicting evidence having similar-looking, non-contiguous, overlapping pieces.</p> <p> At least partly in response to competition from Celera, the IHGP changed its focus from producing finished clones to producing draft clones. To sequence a clone, the IHGP adopted a shotgun approach in miniature. Bits of a clone was read at random, and the bits were stitched together by a computer program into pieces called "contigs." After the shotgun phase, a clone was typically in 5-50 contigs, but the relative order of the contigs was not known. This was the state of the genome when David Haussler first attempted to locate the genes computationally, and he quickly discovered that computational gene-finding was nearly impossible, since the average size of a contig was considerably smaller than the average size of a human gene.</p> + +<a name="push"></a> <h3>Push to the Finish Line</h3> <p> Motivated to prevent Celera and its clients from locking up significant portions of the human genome in patents, Jim Kent dropped his other work in May of 2000 to focus on the assembly problem. In a remarkable display of energy and talent, Kent developed within 4 weeks a 10,000-line computer program that assembled the working draft of the human genome. The program, called GigAssembler, constructed the first working draft of the human genome on June 22, 2000, just days before Celera completed its first assembly. The IHGP working draft combined anonymous genomic information from human volunteers of diverse backgrounds, accepted on a first-come, first-taken basis. The Celera sequence was of a single individual. Since the public consortium finished the genome ahead of the private company, the genome and the information it contains is available free to researchers worldwide. Kent's assembly was celebrated at a White House ceremony on June 26, 2000, announcing the completion of the first drafts of the human genome by the IHGP and Celera.</p> <p> On July 7, 2000, after further examination by the principal scientists of the public genome project, @@ -155,58 +179,60 @@ there remained gaps where DNA sequence was missing, due either to a lack of raw sequence data or ambiguities in the positions of the fragments. With the gene assembly 90% complete, the assembled genome was published along with the findings of hundreds of researchers worldwide in the February 15, 2001 issue of <i>Nature</i>, which was largely devoted to the human genome. In the months following the release of the working draft, the UCSC team worked with other researchers worldwide to fill in the gaps. The resulting finished sequence made its debut in April of 2003. It encompasses 99% of the gene-containing regions of the human genome and is 99.99% accurate.</p> <p> The UCSC Genome Browser was designated as the official repository of the early human genome assembly iterations. Once the human genome sequence became available, other genome browsers also came online, most notably those at the National Center for Biotechnology Information (NCBI) and at the European Bioinformatics Institute (EBI). Reciprocal links provided on each of the three browsers allow researchers to jump from any place in the human genome to the same region on either of the other two browsers.</p> +<a name="ENCODE"></a> <h2>The ENCODE Project</h2> <p> The human genome contains vast amounts of information, and all of the functions of a human cell are implicitly coded in the human genome. With the molecular sequence known, researchers have been mining it for clues as to how the body works in health and in disease. Ultimately laying out the plan for the complex pathways of molecular interactions that the sequence orchestrates. The UCSC Genome Browser aids the worldwide scientific community in its challenge to understand the genome, to probe it with new experimental and informatics methodologies, and to decode the genetic program of the cell.</p> <p> After the sequence of the genome was first available, a researcher's ability to decode that sequence and tap into the wealth of information it holds was still quite limited. The next step beyond viewing the genome is gaining an understanding of the instructions encoded in it. Toward this end, the UCSC Genome Browser group participated as the data collection center for the <a href="https://www.encodeproject.org/" target="_blank">ENCyclopedia Of DNA Elements (ENCODE) project</a>, an international endeavor to generate a comprehensive parts list of all the functional components in the human genome.</p> <p> ENCODE is a scientific reconnaissance mission aimed at discovering all regions of the human genome crucial to biological function. Before ENCODE, scientists focused on finding the genes, or protein-coding regions in DNA sequences, but these account for only about 1.5% of the genetic material of humans and other mammals. Non-coding regions of the genome have important functions, and the ENCODE project is developing a comprehensive "parts list" by identifying and precisely locating all functional elements in the human genome. This project, sponsored by the <a href="https://www.genome.gov/" target="_blank">National Human Genome Research Institute (NHGRI)</a>, involves an international consortium of scientists from government, industry, and academia.</p> +<a name="ucsc"></a> <h3>UC Santa Cruz's role</h3> <p> UC Santa Cruz developed and ran the data coordination center for the ENCODE project from its inception in 2003 through the end of the first production phase in 2012. During that time, the UCSC Genome Browser group directed by Jim Kent with technical management by Kate Rosenbloom provided the database and web interface for all sequence-related data for the ENCODE project. This included integrating the data into the UCSC Human Genome Browser (where it continues to reside) on specialized tracks, and providing further in-depth information on detail pages. UC Santa Cruz also developed, performed, and presented computational and comparative analyses to glean further genomic and functional information from the collective data.</p> <p> UC Santa Cruz worked closely with labs producing data for the ENCODE project and with data analysis groups to define data and metadata reporting standards for a broad range of genomics assays. They implemented data submission and validation pipelines, created and maintained the encodeproject.org website, developed user access tools for ENCODE data, exported all ENCODE data to repositories at @@ -226,31 +252,34 @@ target="_blank">ENCODE data in the UCSC Genome Browser: year 5 update.</a> Nucleic Acids Res. 2013 Jan;41(Database issue):D56-63.</p> <h3>More about the ENCODE Project</h3> <ul> <li> <a href="https://www.encodeproject.org/" target="_blank">ENCODE data portal</a></li> <li> <a href="https://www.nytimes.com/2008/11/11/science/11gene.html" target="_blank">New York Times article: "Now: the rest of the genome"</a></li> <li> <a href="https://www.genome.gov/11009066/" target="_blank">NHGRI announcement of the ENCODE Project</a></li> </ul> +<a name="primer"></a> <h2>UCSC Genome Research Primer</h2> + +<a name="comparative"></a> <h3>Comparative Genomics</h3> <p> Besides developing, supporting, and continuing to improve the genome browser, the UCSC Genome Browser group conducts research into the functional elements of the human genome that have evolved under natural selection. Since the first assembly of the human genome, the UCSC group has added a growing number of species to the UCSC Genome Browser, including roundworm, pufferfish, chicken, mouse, and chimpanzee. Interspecies alignments allow researchers to compare human genes to similar genes in other species. The UCSC Genome Browser allows rapid comparisons between species, which can lead to many different types of new discoveries:</p> <ul> <li> New gene discoveries can result from searching the human genome for sequences that match those with known functions in other organisms. The molecular genetics behind disease development and progression in model organisms can be leveraged to discover potential disease-related genes in humans, moving us closer to diagnostic advances and targeted treatments.</li> @@ -259,30 +288,31 @@ interspecies differences and of short segments in the human genome that have been extremely well-conserved over millions of years of evolution.</li> <li> By searching for the highly conserved segments in the human genome- those that are unchanged from like segments in the genomes of other organisms, we can begin to understand the essential elements of the blueprint for life. Researchers suspect that these highly conserved elements must be essential to function. Genes make up only a small percentage of the unchanged elements, suggesting that other unknown regulatory elements in the genome are also important for function.</li> <li> Searching for genes that have evolved with unusual speed from one organism to another will give clues to essential interspecies differences, such as differences between the human and chimpanzee brain.</li> </ul> +<a name="health"></a> <h3>Possibilities for Health</h3> <p> As we begin to better understand the molecular mechanisms responsible for human disease, entirely new avenues of treatments will be possible. We are only now getting a first glimmer of the molecular functions of a healthy human cell or organ, and we are still a long way from understanding the often subtle and complex ways that these can go awry. Yet knowledge of the human genome puts us on the brink of a revolution in medicine.</p> <p> Rather than relying on trial and error to design and test new drugs, researchers will increasingly use their knowledge of the molecular causes of diseases to design new, targeted therapies. Research based on genome studies and new experimental methods like CRISPR, all viewable on the UCSC Genome Browser, will also form the basis for new diagnoses and therapies for human disease that will transform the practice of medicine in this century.</p> <p> The UCSC Genome Browser supports the latest endeavor of the National Human Genome Research Institute