2321e33442cb48591aae4c29b40424a402b182a7 jnavarr5 Mon Jan 4 15:38:16 2021 -0800 Adding images and captions to the history page. Still need to fix the format/style. refs #20314 diff --git src/hg/htdocs/goldenPath/history.html src/hg/htdocs/goldenPath/history.html index 54b4c6d..4378f13 100755 --- src/hg/htdocs/goldenPath/history.html +++ src/hg/htdocs/goldenPath/history.html @@ -122,30 +122,53 @@ (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> +<div class="row"> + <div class="col-md-6"> + <img class="text-center" alt="Jim next to his computer" src="/images/jim-in-garage.jpg" + style="margin-botton:5px; width:500px"> + <div style="text-align:center; line-height:1"> + <font SIZE=-1> + Jim in his garage sitting next to the computer where he wrote the 10,000 lines of computer + code to assemble the first draft assembly of the human genome. + </font> + </div> + </div> + <div class="col-md-6"> + <img class="text-center" alt="Jim, David, Scot, Patrick, and Gavin at UCSC." + src="/images/Jim-Kent-David-Haussler-Scot-Kennedy-Patrick-Gavin-genome-assembly-era-Group-2000.jpg" + style="margin-botton:5px; width:400px"> + <div style="text-align:center; line-height:1"> + <font SIZE=-1> + Jim Kent, David Haussler, Scot Free Kennedy, and Patrick Gavin at UCSC. + </font> + </div> + </div> +</div> + <a name="celera"></a> <h3>New challenger, Celera Genomics</h3> <p> It was a crucial time for the international project. A private company, <a target="_blank" href="https://en.wikipedia.org/wiki/Celera_Corporation">Celera Genomics</a>, 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" method, 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. A further complication was the fact that Celera had access to the fruits of the public project, while keeping their own results private.</p> @@ -159,65 +182,97 @@ 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 were 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> +<div class="row"> + <div class="col-md-6"> <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 four 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 are 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> + </div> + <div class="col-md-6"> + <img class="text-center" alt="Copy of first draft of the human genome on a CD" + src="/images/genome_cd.jpg" + style="margin-botton:5px; width:400px"> + <div style="text-align:center; line-height:1"> + <font SIZE=-1> + Copy of first draft of the human genome sequence presented to + <a href="https://www.soe.ucsc.edu/news/article/1020" target="_blank">President + Clinton</a> and deposited in the Smithsonian. + </font> + </div> + </div> +</div> + +<div class="row"> + <div class="col-md-6"> <p> On July 7, 2000, after further examination by the principal scientists of the public genome project, and to facilitate the annotation process, the UCSC Genome Browser group released this first working draft on the web at <a href="../" target="_blank">https://genome.ucsc.edu</a>. In the first 24 hours of free and unrestricted access to the human genome, the scientific community downloaded one-half trillion bytes of information from the assembled blueprint of our human species. The initial assembled human genome sequence was referred to as a working draft because 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 <a href="https://www.nature.com/nature/volumes/409/issues/6822" target="_blank">February 15, 2001 issue of <i>Nature</i></a>, 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 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 <a href="https://www.ncbi.nlm.nih.gov/" target="_blank">National Center for Biotechnology Information (NCBI)</a> and at the <a href="https://www.ebi.ac.uk/" target="_blank">European Bioinformatics Institute (EBI)</a>. 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> + </div> + <div class="col-md-6"> + <img class="text-center" alt="David in front of Dell cluster" + src="/images/david_cluster.jpg" + style="margin-botton:5px; width:400px"> + <div style="text-align:center; line-height:1"> + <font SIZE=-1> + David Haussler next to the original Dell computer cluster used for the assembly of the + first human genome. + </font> + </div> + </div> +</div> <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, @@ -227,48 +282,62 @@ 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 serving as the instruction set for when and in which tissues genes are turned on and off. 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> +<div class="row"> + <div class="col-md-6"> <p> UC Santa Cruz developed and ran the data coordination center for the ENCODE project from its inception in 2003 through the <a href="../ENCODE/" target="_blank">end of the first production phase in 2012</a>. 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 to 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 <a href="https://www.encodeproject.org/" target="_blank">encodeproject.org</a> website, developed user access tools for ENCODE data, exported all ENCODE data to repositories at the National Center for Biotechnology Information (NCBI), and provided outreach and tutorial support for the project. </p> + </div> + <div class="col-md-6"> + <img class="text-center" alt="Picture of Kate Rosenbloom from 2003" src="/images/kate2003.jpg" + style="margin-botton:5px; width:250px"> + <div style="text-align:center; line-height:1"> + <font SIZE=-1> + <p class="gbsCaption text-center"> + Picture of Kate Rosenbloom from 2003 while working on the ENCODE Project.</p> + </font> + </div> + </div> +</div> <p> The ENCODE data coordination was passed on to the Michael Cherry laboratory at Stanford University in late 2012. UC Santa Cruz, however, continues to support existing ENCODE data and resources on the UCSC Genome Browser website. Newer ENCODE data of broad interest, particularly integrative and summary data, will be incorporated into the browser.</p> <p> <em>The following paper describes ENCODE resources at UC Santa Cruz:</em></p> <p> Rosenbloom KR, Sloan CA, Malladi VS, Dreszer TR, Learned K, Kirkup VM, Wong MC, Maddren M, Fang R, Heitner SG <em>et al</em>. <a href="https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gks1172" target="_blank"> ENCODE data in the UCSC Genome Browser: year 5 update</a>. <em>Nucleic Acids Res</em>. 2013 Jan;41(Database issue):D56-63. PMID: <a href="https://www.ncbi.nlm.nih.gov/pubmed/23193274" target="_blank">23193274</a>; PMC: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531152/" target="_blank">PMC3531152</a>