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Rosenbloom)] TJ ET 0.271 0.267 0.267 rg BT 429.364 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 434.785 688.195 Td /F1 9.8 Tf [(Pauline A. Fujita)] TJ ET 0.271 0.267 0.267 rg BT 505.774 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 511.195 688.195 Td /F1 9.8 Tf [(Angie S. )] TJ ET BT 26.250 676.290 Td /F1 9.8 Tf [(Hinrichs)] TJ ET 0.271 0.267 0.267 rg BT 61.457 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 66.878 676.290 Td /F1 9.8 Tf [(Matthew L Speir)] TJ ET 0.271 0.267 0.267 rg BT 137.322 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 142.743 676.290 Td /F1 9.8 Tf [(Chris Eisenhart)] TJ ET 0.271 0.267 0.267 rg BT 209.384 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 214.805 676.290 Td /F1 9.8 Tf [(Ann S. Zweig)] TJ ET 0.271 0.267 0.267 rg BT 272.788 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 278.209 676.290 Td /F1 9.8 Tf [(David Haussler)] TJ ET 0.271 0.267 0.267 rg BT 344.305 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 349.726 676.290 Td /F1 9.8 Tf [(W. James Kent)] TJ ET 0.271 0.267 0.267 rg BT 26.250 664.386 Td /F1 9.8 Tf [(Haeussler M, Karolchik D, Clawson H, Raney BJ, Rosenbloom KR, Fujita PA, Hinrichs AS, Speir ML, Eisenhart C, Zweig AS, )] TJ ET BT 26.250 652.481 Td /F1 9.8 Tf [(Haussler D, Kent WJ. The UCSC Ebola Genome Portal. PLOS Currents Outbreaks. 2014 Nov 7 . Edition 1. doi: )] TJ ET BT 26.250 640.576 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.386ab0964ab4d6c8cb550bfb6071d822.)] TJ ET q 15.000 24.954 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 611.474 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 591.519 Td /F1 9.8 Tf [(Background:)] TJ ET BT 26.250 579.615 Td /F1 9.8 Tf [(With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in )] TJ ET BT 26.250 567.710 Td /F1 9.8 Tf [(the generation of much genomic data.)] TJ ET BT 26.250 548.305 Td /F1 9.8 Tf [(Methods:)] TJ ET BT 26.250 536.400 Td /F1 9.8 Tf [(In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have )] TJ ET BT 544.336 536.400 Td /F1 9.8 Tf [(created )] TJ ET BT 26.250 524.496 Td /F1 9.8 Tf [(the University of California Santa Cruz \(UCSC\) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser )] TJ ET BT 26.250 512.591 Td /F1 9.8 Tf [(web tool, which can be used to view the Ebola virus genome sequence from GenBank and nearly 30 annotation tracks )] TJ ET BT 26.250 500.686 Td /F1 9.8 Tf [(generated by mapping external data to the reference sequence. Significant annotations include a multiple alignment comprising )] TJ ET BT 26.250 488.781 Td /F1 9.8 Tf [(102 Ebola genomes from the current outbreak, 56 from previous outbreaks, and 2 Marburg genomes as an outgroup; a gene )] TJ ET BT 26.250 476.877 Td /F1 9.8 Tf [(track curated by NCBI; protein annotations curated by UniProt and antibody-binding epitopes curated by IEDB. We have )] TJ ET BT 26.250 464.972 Td /F1 9.8 Tf [(extended the Genome Browsers multiple alignment color-coding scheme to distinguish mutations resulting from non-)] TJ ET BT 26.250 453.067 Td /F1 9.8 Tf [(synonymous coding changes, synonymous changes, or changes in untranslated regions.)] TJ ET BT 26.250 433.662 Td /F1 9.8 Tf [(Discussion:)] TJ ET BT 26.250 421.758 Td /F1 9.8 Tf [(Our Ebola Genome portal at http://genome.ucsc.edu/ebolaPortal/ links to the Ebola virus Genome Browser and an aggregate of )] TJ ET BT 26.250 409.853 Td /F1 9.8 Tf [(useful information, including a collection of Ebola antibodies we are curating.)] TJ ET BT 26.250 373.250 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 353.296 Td /F1 9.8 Tf [(This work is financially supported primarily by funds from the National Human Genome Research Institute \(grant number )] TJ ET BT 26.250 341.391 Td /F1 9.8 Tf [(5U4HG002371\) and in part by royalties. M.H., H.C., B.J.R, K.R.R., P.A.F., A.S.H,D.K., A.S.Z., D.H., and W.J.K receive royalties )] TJ ET BT 26.250 329.487 Td /F1 9.8 Tf [(from the sale of UCSC Genome Browser source code licenses to commercial entities. The funders had no role in study design, )] TJ ET BT 26.250 317.582 Td /F1 9.8 Tf [(data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 288.479 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 268.525 Td /F1 9.8 Tf [(The Ebola epidemic continues to grow in West Africa. The U.S. Centers for Disease Control \(CDC\) estimated the occurrence of )] TJ ET BT 26.250 256.620 Td /F1 9.8 Tf [(21,000 cases in Sierra Leone and Liberia alone by Sept. 30, 2014, surging to 1,400,000 cases by Jan. 20, 2014, if the epidemic )] TJ ET BT 26.250 244.716 Td /F1 9.8 Tf [(continues to grow at the current pace)] TJ ET 0.267 0.267 0.267 rg BT 186.667 246.223 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 191.485 244.716 Td /F1 9.8 Tf [(. Against such a backdrop, research on Ebola antibodies and vaccines is a high priority. )] TJ ET BT 26.250 232.811 Td /F1 9.8 Tf [(Much of the research on the current epidemic involves genomic sequencing of the virus, including three genomes from Guinea)] TJ ET 0.267 0.267 0.267 rg BT 570.865 234.318 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 220.906 Td /F1 9.8 Tf [(and 99 genomes from Sierra Leone)] TJ ET 0.267 0.267 0.267 rg BT 179.618 222.413 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 184.436 220.906 Td /F1 9.8 Tf [(. Sequence annotations are available from established database curation teams: UniProt)] TJ ET 0.267 0.267 0.267 rg BT 566.500 222.413 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 26.250 209.001 Td /F1 9.8 Tf [(has manually annotated the protein sequences and the Immune Epitope and Analysis Resource)] TJ ET 0.267 0.267 0.267 rg BT 439.757 210.509 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 444.576 209.001 Td /F1 9.8 Tf [( has collected epitope )] TJ ET BT 26.250 197.097 Td /F1 9.8 Tf [(sequences from previously published studies. These diverse datasets can all be mapped to the genome sequence. However, )] TJ ET BT 26.250 185.192 Td /F1 9.8 Tf [(existing tools such as the NCBI Virus Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 264.667 186.699 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 269.485 185.192 Td /F1 9.8 Tf [( and the Viral Genome Organizer)] TJ ET 0.267 0.267 0.267 rg BT 412.547 186.699 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 417.366 185.192 Td /F1 9.8 Tf [( show only gene models. VIPR)] TJ ET 0.267 0.267 0.267 rg BT 550.132 186.699 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 559.769 185.192 Td /F1 9.8 Tf [( is a )] TJ ET BT 26.250 173.287 Td /F1 9.8 Tf [(toolset to annotate sequences but the results are not available instantly and does not merge them into an integrated zoomable )] TJ ET BT 26.250 161.382 Td /F1 9.8 Tf [(view. Reasoning that the University of California Santa Cruz \(UCSC\) Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 400.114 162.890 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 404.932 165.271 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.342 162.890 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 412.160 161.382 Td /F1 9.8 Tf [( could be adapted quickly to help with )] TJ ET BT 26.250 149.478 Td /F1 9.8 Tf [(analysis of the current outbreak, we built an Ebola Genome Browser that aggregates a wide range of data from sources )] TJ ET BT 26.250 137.573 Td /F1 9.8 Tf [(worldwide.)] TJ ET BT 26.250 118.168 Td /F1 9.8 Tf [(The UCSC Genome Browser is a mature web tool for rapid and reliable display of any requested portion of a genome at any )] TJ ET BT 26.250 106.263 Td /F1 9.8 Tf [(scale. The genome itself forms the horizontal axis that can be zoomed and scrolled. The vertical axis is a stack of annotation )] TJ ET BT 26.250 94.359 Td /F1 9.8 Tf [(tracks, each containing a particular type of data. Examples of common annotation track types for a typical vertebrate genome )] TJ ET BT 26.250 82.454 Td /F1 9.8 Tf [(include genes, comparative multiple alignments of many genomes, and SNPs. The tracks can be displayed at various levels of )] TJ ET BT 26.250 70.549 Td /F1 9.8 Tf [(detail, and clicking on an item in a track displays a page of information about that item.)] TJ ET BT 26.250 51.144 Td /F1 9.8 Tf [(We have adapted the Genome Browser to support the display of the Ebola virus genome and a diverse set of annotations. In )] TJ ET BT 26.250 39.240 Td /F1 9.8 Tf [(addition to the Ebola Genome Browser, we constructed an Ebola Portal page that wraps around the browser and other collected )] TJ ET Q q 15.000 709.302 577.500 28.698 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(The UCSC Ebola Genome Portal)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 700.036 Td /F3 9.8 Tf [(November 7, 2014)] TJ ET BT 91.635 700.036 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 96.510 700.036 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 688.195 Td /F1 9.8 Tf [(Maximilian Haeussler)] TJ ET 0.271 0.267 0.267 rg BT 118.885 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 124.306 688.195 Td /F1 9.8 Tf [(Donna Karolchik)] TJ ET 0.271 0.267 0.267 rg BT 195.832 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 201.253 688.195 Td /F1 9.8 Tf [(Hiram Clawson)] TJ ET 0.271 0.267 0.267 rg BT 267.338 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 272.759 688.195 Td /F1 9.8 Tf [(Brian J Raney)] TJ ET 0.271 0.267 0.267 rg BT 333.989 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 339.410 688.195 Td /F1 9.8 Tf [(Kate R. Rosenbloom)] TJ ET 0.271 0.267 0.267 rg BT 429.364 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 434.785 688.195 Td /F1 9.8 Tf [(Pauline A. Fujita)] TJ ET 0.271 0.267 0.267 rg BT 505.774 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 511.195 688.195 Td /F1 9.8 Tf [(Angie S. )] TJ ET BT 26.250 676.290 Td /F1 9.8 Tf [(Hinrichs)] TJ ET 0.271 0.267 0.267 rg BT 61.457 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 66.878 676.290 Td /F1 9.8 Tf [(Matthew L Speir)] TJ ET 0.271 0.267 0.267 rg BT 137.322 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 142.743 676.290 Td /F1 9.8 Tf [(Chris Eisenhart)] TJ ET 0.271 0.267 0.267 rg BT 209.384 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 214.805 676.290 Td /F1 9.8 Tf [(Ann S. Zweig)] TJ ET 0.271 0.267 0.267 rg BT 272.788 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 278.209 676.290 Td /F1 9.8 Tf [(David Haussler)] TJ ET 0.271 0.267 0.267 rg BT 344.305 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 349.726 676.290 Td /F1 9.8 Tf [(W. James Kent)] TJ ET 0.271 0.267 0.267 rg BT 26.250 664.386 Td /F1 9.8 Tf [(Haeussler M, Karolchik D, Clawson H, Raney BJ, Rosenbloom KR, Fujita PA, Hinrichs AS, Speir ML, Eisenhart C, Zweig AS, )] TJ ET BT 26.250 652.481 Td /F1 9.8 Tf [(Haussler D, Kent WJ. The UCSC Ebola Genome Portal. PLOS Currents Outbreaks. 2014 Nov 7 . Edition 1. doi: )] TJ ET BT 26.250 640.576 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.386ab0964ab4d6c8cb550bfb6071d822.)] TJ ET q 15.000 24.954 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 611.474 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 591.519 Td /F1 9.8 Tf [(Background:)] TJ ET BT 26.250 579.615 Td /F1 9.8 Tf [(With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in )] TJ ET BT 26.250 567.710 Td /F1 9.8 Tf [(the generation of much genomic data.)] TJ ET BT 26.250 548.305 Td /F1 9.8 Tf [(Methods:)] TJ ET BT 26.250 536.400 Td /F1 9.8 Tf [(In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have )] TJ ET BT 544.336 536.400 Td /F1 9.8 Tf [(created )] TJ ET BT 26.250 524.496 Td /F1 9.8 Tf [(the University of California Santa Cruz \(UCSC\) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser )] TJ ET BT 26.250 512.591 Td /F1 9.8 Tf [(web tool, which can be used to view the Ebola virus genome sequence from GenBank and nearly 30 annotation tracks )] TJ ET BT 26.250 500.686 Td /F1 9.8 Tf [(generated by mapping external data to the reference sequence. Significant annotations include a multiple alignment comprising )] TJ ET BT 26.250 488.781 Td /F1 9.8 Tf [(102 Ebola genomes from the current outbreak, 56 from previous outbreaks, and 2 Marburg genomes as an outgroup; a gene )] TJ ET BT 26.250 476.877 Td /F1 9.8 Tf [(track curated by NCBI; protein annotations curated by UniProt and antibody-binding epitopes curated by IEDB. We have )] TJ ET BT 26.250 464.972 Td /F1 9.8 Tf [(extended the Genome Browsers multiple alignment color-coding scheme to distinguish mutations resulting from non-)] TJ ET BT 26.250 453.067 Td /F1 9.8 Tf [(synonymous coding changes, synonymous changes, or changes in untranslated regions.)] TJ ET BT 26.250 433.662 Td /F1 9.8 Tf [(Discussion:)] TJ ET BT 26.250 421.758 Td /F1 9.8 Tf [(Our Ebola Genome portal at http://genome.ucsc.edu/ebolaPortal/ links to the Ebola virus Genome Browser and an aggregate of )] TJ ET BT 26.250 409.853 Td /F1 9.8 Tf [(useful information, including a collection of Ebola antibodies we are curating.)] TJ ET BT 26.250 373.250 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 353.296 Td /F1 9.8 Tf [(This work is financially supported primarily by funds from the National Human Genome Research Institute \(grant number )] TJ ET BT 26.250 341.391 Td /F1 9.8 Tf [(5U4HG002371\) and in part by royalties. M.H., H.C., B.J.R, K.R.R., P.A.F., A.S.H,D.K., A.S.Z., D.H., and W.J.K receive royalties )] TJ ET BT 26.250 329.487 Td /F1 9.8 Tf [(from the sale of UCSC Genome Browser source code licenses to commercial entities. The funders had no role in study design, )] TJ ET BT 26.250 317.582 Td /F1 9.8 Tf [(data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 288.479 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 268.525 Td /F1 9.8 Tf [(The Ebola epidemic continues to grow in West Africa. The U.S. Centers for Disease Control \(CDC\) estimated the occurrence of )] TJ ET BT 26.250 256.620 Td /F1 9.8 Tf [(21,000 cases in Sierra Leone and Liberia alone by Sept. 30, 2014, surging to 1,400,000 cases by Jan. 20, 2014, if the epidemic )] TJ ET BT 26.250 244.716 Td /F1 9.8 Tf [(continues to grow at the current pace)] TJ ET 0.267 0.267 0.267 rg BT 186.667 246.223 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 191.485 244.716 Td /F1 9.8 Tf [(. Against such a backdrop, research on Ebola antibodies and vaccines is a high priority. )] TJ ET BT 26.250 232.811 Td /F1 9.8 Tf [(Much of the research on the current epidemic involves genomic sequencing of the virus, including three genomes from Guinea)] TJ ET 0.267 0.267 0.267 rg BT 570.865 234.318 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 220.906 Td /F1 9.8 Tf [(and 99 genomes from Sierra Leone)] TJ ET 0.267 0.267 0.267 rg BT 179.618 222.413 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 184.436 220.906 Td /F1 9.8 Tf [(. Sequence annotations are available from established database curation teams: UniProt)] TJ ET 0.267 0.267 0.267 rg BT 566.500 222.413 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 26.250 209.001 Td /F1 9.8 Tf [(has manually annotated the protein sequences and the Immune Epitope and Analysis Resource)] TJ ET 0.267 0.267 0.267 rg BT 439.757 210.509 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 444.576 209.001 Td /F1 9.8 Tf [( has collected epitope )] TJ ET BT 26.250 197.097 Td /F1 9.8 Tf [(sequences from previously published studies. These diverse datasets can all be mapped to the genome sequence. However, )] TJ ET BT 26.250 185.192 Td /F1 9.8 Tf [(existing tools such as the NCBI Virus Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 264.667 186.699 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 269.485 185.192 Td /F1 9.8 Tf [( and the Viral Genome Organizer)] TJ ET 0.267 0.267 0.267 rg BT 412.547 186.699 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 417.366 185.192 Td /F1 9.8 Tf [( show only gene models. VIPR)] TJ ET 0.267 0.267 0.267 rg BT 550.132 186.699 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 559.769 185.192 Td /F1 9.8 Tf [( is a )] TJ ET BT 26.250 173.287 Td /F1 9.8 Tf [(toolset to annotate sequences but the results are not available instantly and does not merge them into an integrated zoomable )] TJ ET BT 26.250 161.382 Td /F1 9.8 Tf [(view. Reasoning that the University of California Santa Cruz \(UCSC\) Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 400.114 162.890 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 404.932 165.271 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.342 162.890 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 412.160 161.382 Td /F1 9.8 Tf [( could be adapted quickly to help with )] TJ ET BT 26.250 149.478 Td /F1 9.8 Tf [(analysis of the current outbreak, we built an Ebola Genome Browser that aggregates a wide range of data from sources )] TJ ET BT 26.250 137.573 Td /F1 9.8 Tf [(worldwide.)] TJ ET BT 26.250 118.168 Td /F1 9.8 Tf [(The UCSC Genome Browser is a mature web tool for rapid and reliable display of any requested portion of a genome at any )] TJ ET BT 26.250 106.263 Td /F1 9.8 Tf [(scale. The genome itself forms the horizontal axis that can be zoomed and scrolled. The vertical axis is a stack of annotation )] TJ ET BT 26.250 94.359 Td /F1 9.8 Tf [(tracks, each containing a particular type of data. Examples of common annotation track types for a typical vertebrate genome )] TJ ET BT 26.250 82.454 Td /F1 9.8 Tf [(include genes, comparative multiple alignments of many genomes, and SNPs. The tracks can be displayed at various levels of )] TJ ET BT 26.250 70.549 Td /F1 9.8 Tf [(detail, and clicking on an item in a track displays a page of information about that item.)] TJ ET BT 26.250 51.144 Td /F1 9.8 Tf [(We have adapted the Genome Browser to support the display of the Ebola virus genome and a diverse set of annotations. In )] TJ ET BT 26.250 39.240 Td /F1 9.8 Tf [(addition to the Ebola Genome Browser, we constructed an Ebola Portal page that wraps around the browser and other collected )] TJ ET Q q 15.000 709.302 577.500 28.698 re W n 0.267 0.267 0.267 rg BT 15.000 718.042 Td /F2 21.0 Tf [(The UCSC Ebola Genome Portal)] TJ ET Q 0.271 0.267 0.267 rg BT 15.000 700.036 Td /F3 9.8 Tf [(November 7, 2014)] TJ ET BT 91.635 700.036 Td /F3 9.8 Tf [()] TJ ET 0.267 0.267 0.267 rg BT 96.510 700.036 Td /F3 9.8 Tf [(Research Article)] TJ ET BT 26.250 688.195 Td /F1 9.8 Tf [(Maximilian Haeussler)] TJ ET 0.271 0.267 0.267 rg BT 118.885 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 124.306 688.195 Td /F1 9.8 Tf [(Donna Karolchik)] TJ ET 0.271 0.267 0.267 rg BT 195.832 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 201.253 688.195 Td /F1 9.8 Tf [(Hiram Clawson)] TJ ET 0.271 0.267 0.267 rg BT 267.338 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 272.759 688.195 Td /F1 9.8 Tf [(Brian J Raney)] TJ ET 0.271 0.267 0.267 rg BT 333.989 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 339.410 688.195 Td /F1 9.8 Tf [(Kate R. Rosenbloom)] TJ ET 0.271 0.267 0.267 rg BT 429.364 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 434.785 688.195 Td /F1 9.8 Tf [(Pauline A. Fujita)] TJ ET 0.271 0.267 0.267 rg BT 505.774 688.195 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 511.195 688.195 Td /F1 9.8 Tf [(Angie S. )] TJ ET BT 26.250 676.290 Td /F1 9.8 Tf [(Hinrichs)] TJ ET 0.271 0.267 0.267 rg BT 61.457 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 66.878 676.290 Td /F1 9.8 Tf [(Matthew L Speir)] TJ ET 0.271 0.267 0.267 rg BT 137.322 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 142.743 676.290 Td /F1 9.8 Tf [(Chris Eisenhart)] TJ ET 0.271 0.267 0.267 rg BT 209.384 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 214.805 676.290 Td /F1 9.8 Tf [(Ann S. Zweig)] TJ ET 0.271 0.267 0.267 rg BT 272.788 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 278.209 676.290 Td /F1 9.8 Tf [(David Haussler)] TJ ET 0.271 0.267 0.267 rg BT 344.305 676.290 Td /F1 9.8 Tf [(, )] TJ ET 0.267 0.267 0.267 rg BT 349.726 676.290 Td /F1 9.8 Tf [(W. James Kent)] TJ ET 0.271 0.267 0.267 rg BT 26.250 664.386 Td /F1 9.8 Tf [(Haeussler M, Karolchik D, Clawson H, Raney BJ, Rosenbloom KR, Fujita PA, Hinrichs AS, Speir ML, Eisenhart C, Zweig AS, )] TJ ET BT 26.250 652.481 Td /F1 9.8 Tf [(Haussler D, Kent WJ. The UCSC Ebola Genome Portal. PLOS Currents Outbreaks. 2014 Nov 7 . Edition 1. doi: )] TJ ET BT 26.250 640.576 Td /F1 9.8 Tf [(10.1371/currents.outbreaks.386ab0964ab4d6c8cb550bfb6071d822.)] TJ ET q 15.000 24.954 577.500 613.241 re W n 0.271 0.267 0.267 rg BT 26.250 611.474 Td /F4 12.0 Tf [(Abstract)] TJ ET BT 26.250 591.519 Td /F1 9.8 Tf [(Background:)] TJ ET BT 26.250 579.615 Td /F1 9.8 Tf [(With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in )] TJ ET BT 26.250 567.710 Td /F1 9.8 Tf [(the generation of much genomic data.)] TJ ET BT 26.250 548.305 Td /F1 9.8 Tf [(Methods:)] TJ ET BT 26.250 536.400 Td /F1 9.8 Tf [(In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have )] TJ ET BT 544.336 536.400 Td /F1 9.8 Tf [(created )] TJ ET BT 26.250 524.496 Td /F1 9.8 Tf [(the University of California Santa Cruz \(UCSC\) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser )] TJ ET BT 26.250 512.591 Td /F1 9.8 Tf [(web tool, which can be used to view the Ebola virus genome sequence from GenBank and nearly 30 annotation tracks )] TJ ET BT 26.250 500.686 Td /F1 9.8 Tf [(generated by mapping external data to the reference sequence. Significant annotations include a multiple alignment comprising )] TJ ET BT 26.250 488.781 Td /F1 9.8 Tf [(102 Ebola genomes from the current outbreak, 56 from previous outbreaks, and 2 Marburg genomes as an outgroup; a gene )] TJ ET BT 26.250 476.877 Td /F1 9.8 Tf [(track curated by NCBI; protein annotations curated by UniProt and antibody-binding epitopes curated by IEDB. We have )] TJ ET BT 26.250 464.972 Td /F1 9.8 Tf [(extended the Genome Browsers multiple alignment color-coding scheme to distinguish mutations resulting from non-)] TJ ET BT 26.250 453.067 Td /F1 9.8 Tf [(synonymous coding changes, synonymous changes, or changes in untranslated regions.)] TJ ET BT 26.250 433.662 Td /F1 9.8 Tf [(Discussion:)] TJ ET BT 26.250 421.758 Td /F1 9.8 Tf [(Our Ebola Genome portal at http://genome.ucsc.edu/ebolaPortal/ links to the Ebola virus Genome Browser and an aggregate of )] TJ ET BT 26.250 409.853 Td /F1 9.8 Tf [(useful information, including a collection of Ebola antibodies we are curating.)] TJ ET BT 26.250 373.250 Td /F4 12.0 Tf [(Funding Statement)] TJ ET BT 26.250 353.296 Td /F1 9.8 Tf [(This work is financially supported primarily by funds from the National Human Genome Research Institute \(grant number )] TJ ET BT 26.250 341.391 Td /F1 9.8 Tf [(5U4HG002371\) and in part by royalties. M.H., H.C., B.J.R, K.R.R., P.A.F., A.S.H,D.K., A.S.Z., D.H., and W.J.K receive royalties )] TJ ET BT 26.250 329.487 Td /F1 9.8 Tf [(from the sale of UCSC Genome Browser source code licenses to commercial entities. The funders had no role in study design, )] TJ ET BT 26.250 317.582 Td /F1 9.8 Tf [(data collection and analysis, decision to publish, or preparation of the manuscript.)] TJ ET BT 26.250 288.479 Td /F4 12.0 Tf [(Introduction)] TJ ET BT 26.250 268.525 Td /F1 9.8 Tf [(The Ebola epidemic continues to grow in West Africa. The U.S. Centers for Disease Control \(CDC\) estimated the occurrence of )] TJ ET BT 26.250 256.620 Td /F1 9.8 Tf [(21,000 cases in Sierra Leone and Liberia alone by Sept. 30, 2014, surging to 1,400,000 cases by Jan. 20, 2014, if the epidemic )] TJ ET BT 26.250 244.716 Td /F1 9.8 Tf [(continues to grow at the current pace)] TJ ET 0.267 0.267 0.267 rg BT 186.667 246.223 Td /F4 8.7 Tf [(1)] TJ ET 0.271 0.267 0.267 rg BT 191.485 244.716 Td /F1 9.8 Tf [(. Against such a backdrop, research on Ebola antibodies and vaccines is a high priority. )] TJ ET BT 26.250 232.811 Td /F1 9.8 Tf [(Much of the research on the current epidemic involves genomic sequencing of the virus, including three genomes from Guinea)] TJ ET 0.267 0.267 0.267 rg BT 570.865 234.318 Td /F4 8.7 Tf [(2)] TJ ET 0.271 0.267 0.267 rg BT 26.250 220.906 Td /F1 9.8 Tf [(and 99 genomes from Sierra Leone)] TJ ET 0.267 0.267 0.267 rg BT 179.618 222.413 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 184.436 220.906 Td /F1 9.8 Tf [(. Sequence annotations are available from established database curation teams: UniProt)] TJ ET 0.267 0.267 0.267 rg BT 566.500 222.413 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 26.250 209.001 Td /F1 9.8 Tf [(has manually annotated the protein sequences and the Immune Epitope and Analysis Resource)] TJ ET 0.267 0.267 0.267 rg BT 439.757 210.509 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 444.576 209.001 Td /F1 9.8 Tf [( has collected epitope )] TJ ET BT 26.250 197.097 Td /F1 9.8 Tf [(sequences from previously published studies. These diverse datasets can all be mapped to the genome sequence. However, )] TJ ET BT 26.250 185.192 Td /F1 9.8 Tf [(existing tools such as the NCBI Virus Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 264.667 186.699 Td /F4 8.7 Tf [(6)] TJ ET 0.271 0.267 0.267 rg BT 269.485 185.192 Td /F1 9.8 Tf [( and the Viral Genome Organizer)] TJ ET 0.267 0.267 0.267 rg BT 412.547 186.699 Td /F4 8.7 Tf [(7)] TJ ET 0.271 0.267 0.267 rg BT 417.366 185.192 Td /F1 9.8 Tf [( show only gene models. VIPR)] TJ ET 0.267 0.267 0.267 rg BT 550.132 186.699 Td /F4 8.7 Tf [(22)] TJ ET 0.271 0.267 0.267 rg BT 559.769 185.192 Td /F1 9.8 Tf [( is a )] TJ ET BT 26.250 173.287 Td /F1 9.8 Tf [(toolset to annotate sequences but the results are not available instantly and does not merge them into an integrated zoomable )] TJ ET BT 26.250 161.382 Td /F1 9.8 Tf [(view. Reasoning that the University of California Santa Cruz \(UCSC\) Genome Browser)] TJ ET 0.267 0.267 0.267 rg BT 400.114 162.890 Td /F4 8.7 Tf [(8)] TJ ET 0.271 0.267 0.267 rg BT 404.932 165.271 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 407.342 162.890 Td /F4 8.7 Tf [(9)] TJ ET 0.271 0.267 0.267 rg BT 412.160 161.382 Td /F1 9.8 Tf [( could be adapted quickly to help with )] TJ ET BT 26.250 149.478 Td /F1 9.8 Tf [(analysis of the current outbreak, we built an Ebola Genome Browser that aggregates a wide range of data from sources )] TJ ET BT 26.250 137.573 Td /F1 9.8 Tf [(worldwide.)] TJ ET BT 26.250 118.168 Td /F1 9.8 Tf [(The UCSC Genome Browser is a mature web tool for rapid and reliable display of any requested portion of a genome at any )] TJ ET BT 26.250 106.263 Td /F1 9.8 Tf [(scale. The genome itself forms the horizontal axis that can be zoomed and scrolled. The vertical axis is a stack of annotation )] TJ ET BT 26.250 94.359 Td /F1 9.8 Tf [(tracks, each containing a particular type of data. Examples of common annotation track types for a typical vertebrate genome )] TJ ET BT 26.250 82.454 Td /F1 9.8 Tf [(include genes, comparative multiple alignments of many genomes, and SNPs. The tracks can be displayed at various levels of )] TJ ET BT 26.250 70.549 Td /F1 9.8 Tf [(detail, and clicking on an item in a track displays a page of information about that item.)] TJ ET BT 26.250 51.144 Td /F1 9.8 Tf [(We have adapted the Genome Browser to support the display of the Ebola virus genome and a diverse set of annotations. 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These include a set of sequences of antibodies that bind Ebola, for use in research into vaccines and antiserum type )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(therapies and links to many other Ebola resources.)] TJ ET BT 26.250 718.969 Td /F4 12.0 Tf [(Materials and Methods)] TJ ET BT 26.250 699.015 Td /F1 9.8 Tf [(We started with the UCSC Genome Browser code base, primarily written in C, which includes utilities for transforming data from )] TJ ET BT 26.250 687.110 Td /F1 9.8 Tf [(one format to another, tools for loading the MySQL database, and CGI programs that create web pages based on the contents )] TJ ET BT 26.250 675.205 Td /F1 9.8 Tf [(of the database. 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This allowed us to quickly import the extensive set )] TJ ET BT 26.250 608.181 Td /F1 9.8 Tf [(of 99 Ebola genomes from Gire et al. \(2014\))] TJ ET 0.267 0.267 0.267 rg BT 216.463 609.689 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 221.281 608.181 Td /F1 9.8 Tf [( without reformatting. We next ran our multiz pipeline)] TJ ET 0.267 0.267 0.267 rg BT 448.866 609.689 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 458.503 608.181 Td /F1 9.8 Tf [( on the viral genomes to )] TJ ET BT 26.250 596.277 Td /F1 9.8 Tf [(align them to the reference sequence, and used UCSC tools to add information from the GenBank gene annotation. We wrote )] TJ ET BT 26.250 584.372 Td /F1 9.8 Tf [(various text-processing utilities to import data from UniProt)] TJ ET 0.267 0.267 0.267 rg BT 278.746 585.879 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 283.564 584.372 Td /F1 9.8 Tf [(, the Immune Epitope Database \(IEDB\))] TJ ET 0.267 0.267 0.267 rg BT 452.639 585.879 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 457.458 584.372 Td /F1 9.8 Tf [( and the Protein Data Bank )] TJ ET BT 26.250 572.467 Td /F1 9.8 Tf [(\(PDB\))] TJ ET 0.267 0.267 0.267 rg BT 52.790 573.974 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 62.427 572.467 Td /F1 9.8 Tf [(, and used HMMER3)] TJ ET 0.267 0.267 0.267 rg BT 152.917 573.974 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 162.554 572.467 Td /F1 9.8 Tf [( to align protein domain models from Pfam)] TJ ET 0.267 0.267 0.267 rg BT 345.708 573.974 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 355.345 572.467 Td /F1 9.8 Tf [( against the NCBI Ebola gene set. All tracks were )] TJ ET BT 26.250 560.562 Td /F1 9.8 Tf [(described using the Genome Browser trackDb system)] TJ ET 0.267 0.267 0.267 rg BT 259.246 562.070 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 268.883 560.562 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 523.960 Td /F4 12.0 Tf [(Results)] TJ ET BT 26.250 504.006 Td /F4 9.8 Tf [(An Ebola reference genome browser)] TJ ET BT 26.250 484.601 Td /F1 9.8 Tf [(We have successfully produced a UCSC Genome Browser on the Ebola virus genome \(Figure 1\). The multiple-alignment )] TJ ET BT 26.250 472.696 Td /F1 9.8 Tf [(display was extended specifically for Ebola to show the effects of nucleotide mutations on viral proteins \(non-synonymous, )] TJ ET BT 26.250 460.791 Td /F1 9.8 Tf [(synonymous, stop, etc.\). 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These include a set of sequences of antibodies that bind Ebola, for use in research into vaccines and antiserum type )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(therapies and links to many other Ebola resources.)] TJ ET BT 26.250 718.969 Td /F4 12.0 Tf [(Materials and Methods)] TJ ET BT 26.250 699.015 Td /F1 9.8 Tf [(We started with the UCSC Genome Browser code base, primarily written in C, which includes utilities for transforming data from )] TJ ET BT 26.250 687.110 Td /F1 9.8 Tf [(one format to another, tools for loading the MySQL database, and CGI programs that create web pages based on the contents )] TJ ET BT 26.250 675.205 Td /F1 9.8 Tf [(of the database. The source code, available at )] TJ ET 0.267 0.267 0.267 rg BT 228.952 675.205 Td /F1 9.8 Tf [(https://genome-store.ucsc.edu/)] TJ ET 0.271 0.267 0.267 rg BT 362.810 675.205 Td /F1 9.8 Tf [(, is free for academic and non-profit use, but )] TJ ET BT 26.250 663.300 Td /F1 9.8 Tf [(requires licensing for commercial use.)] TJ ET BT 26.250 643.896 Td /F1 9.8 Tf [(The UCSC Genome Browser displays centers around a reference genome assembly to which all annotations are aligned. After )] TJ ET BT 26.250 631.991 Td /F1 9.8 Tf [(conversations on the compatibility of annotations with Dr. Pardis Sabeti from the Broad Institute, we decided to use the )] TJ ET BT 26.250 620.086 Td /F1 9.8 Tf [(sequence from GenBank accession KM034562.1 as our reference sequence. This allowed us to quickly import the extensive set )] TJ ET BT 26.250 608.181 Td /F1 9.8 Tf [(of 99 Ebola genomes from Gire et al. \(2014\))] TJ ET 0.267 0.267 0.267 rg BT 216.463 609.689 Td /F4 8.7 Tf [(3)] TJ ET 0.271 0.267 0.267 rg BT 221.281 608.181 Td /F1 9.8 Tf [( without reformatting. We next ran our multiz pipeline)] TJ ET 0.267 0.267 0.267 rg BT 448.866 609.689 Td /F4 8.7 Tf [(10)] TJ ET 0.271 0.267 0.267 rg BT 458.503 608.181 Td /F1 9.8 Tf [( on the viral genomes to )] TJ ET BT 26.250 596.277 Td /F1 9.8 Tf [(align them to the reference sequence, and used UCSC tools to add information from the GenBank gene annotation. We wrote )] TJ ET BT 26.250 584.372 Td /F1 9.8 Tf [(various text-processing utilities to import data from UniProt)] TJ ET 0.267 0.267 0.267 rg BT 278.746 585.879 Td /F4 8.7 Tf [(4)] TJ ET 0.271 0.267 0.267 rg BT 283.564 584.372 Td /F1 9.8 Tf [(, the Immune Epitope Database \(IEDB\))] TJ ET 0.267 0.267 0.267 rg BT 452.639 585.879 Td /F4 8.7 Tf [(5)] TJ ET 0.271 0.267 0.267 rg BT 457.458 584.372 Td /F1 9.8 Tf [( and the Protein Data Bank )] TJ ET BT 26.250 572.467 Td /F1 9.8 Tf [(\(PDB\))] TJ ET 0.267 0.267 0.267 rg BT 52.790 573.974 Td /F4 8.7 Tf [(11)] TJ ET 0.271 0.267 0.267 rg BT 62.427 572.467 Td /F1 9.8 Tf [(, and used HMMER3)] TJ ET 0.267 0.267 0.267 rg BT 152.917 573.974 Td /F4 8.7 Tf [(12)] TJ ET 0.271 0.267 0.267 rg BT 162.554 572.467 Td /F1 9.8 Tf [( to align protein domain models from Pfam)] TJ ET 0.267 0.267 0.267 rg BT 345.708 573.974 Td /F4 8.7 Tf [(13)] TJ ET 0.271 0.267 0.267 rg BT 355.345 572.467 Td /F1 9.8 Tf [( against the NCBI Ebola gene set. All tracks were )] TJ ET BT 26.250 560.562 Td /F1 9.8 Tf [(described using the Genome Browser trackDb system)] TJ ET 0.267 0.267 0.267 rg BT 259.246 562.070 Td /F4 8.7 Tf [(14)] TJ ET 0.271 0.267 0.267 rg BT 268.883 560.562 Td /F1 9.8 Tf [(.)] TJ ET BT 26.250 523.960 Td /F4 12.0 Tf [(Results)] TJ ET BT 26.250 504.006 Td /F4 9.8 Tf [(An Ebola reference genome browser)] TJ ET BT 26.250 484.601 Td /F1 9.8 Tf [(We have successfully produced a UCSC Genome Browser on the Ebola virus genome \(Figure 1\). The multiple-alignment )] TJ ET BT 26.250 472.696 Td /F1 9.8 Tf [(display was extended specifically for Ebola to show the effects of nucleotide mutations on viral proteins \(non-synonymous, )] TJ ET BT 26.250 460.791 Td /F1 9.8 Tf [(synonymous, stop, etc.\). 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Y1o,C5G5".\~4!KS'MՀkzP_U%]ITQ-~FXj 6v*)0O5Wdv."BؘC-EK˪U1MjuKK˪ySJ˪եh?-j+zM't+#LTEˏݦtpV$"ѵRx{+i1\[. #ܸSk)Ze#_nS݀a]Y]"0^Zf[MJ3#GaKΗJV]$+cX?`dqx JkRղ(DQQSG=5m\϶j5yAEl[ּ!gƗW*:piYQS~jUdʴj^VgE56Z}$y.HOuMuT>niPRD50A5ٰ7iX`5"NCpM(_|h߀ 7 c.SA h ·`PJ5ˁ=6uxKVw]]H"u-a(?hr*RHP5L}6xSJ *PS (W U3aWŔ>bEag!G2ȧEZ6sõb#UABUTPQJQLjo}(F9l+ 1 6[c'AR 6:%c- EB%&[A`=l֘3*^&ZR XAA.mj @+rELW<`A 5] L1=B) ˅rl]>B o߄bIQJpBN J& pqÇ] /P@*t\* U>jzA{p_;m^C/\X~E۶JfLMnF\[DqB?PIy*ûW΍5R9q}O!.dp~unoǭ?ƎSRIPEQBU_2;D}cl@*^}g~ߧsR@\'bVVB9JIۋ:/F&,=-]827{<[ERpT #/݃\'}mYu⩇p%M;/O}OH$|ޮoM@!J LdU?9}йo CcW0]ɷcQ|xSGt,|UBgO^# Pî.rJRӱ?rB$vsx7c_{}{_JŸd+D۶85uc3j73hvva_bn̢quċ[?2BK=Ԗ6pۏǨ~~8 =7CLZPxԠFĥ$Q3ߩO|@TA yP=OS-C 9 LX/~E 8tFmh[B:|kYŶ"=G)CB19NU }`,74HݳPTf$zte8%tXm oab7 ߀Yѩ`iH+!V-JF-ʊ`aق}G`01t`pG{`Up <A:S~1dV۱@4A|޷Yx4*YEf8w> Çb|/fab7nj:v` |tf?I,wab}SHgF\t̥9;(cTA2yTaF3;? t,"a4tGރ7 M*]8:sO|tσ|/'`z4K=B"D&1?L99ѥvxjp[;Dp]cuΞMU*F4M?%2Hgmz#0\ΈUy<{0|ꝡ=di1:/Hz9?@7FgQ29R7PrVUv$VKS; @y:y stv? m'6H1JI\ýֳWp踈#7Qfb+`.jcjy&^ ou!Im x !7oǾWoG6*H[YN_<WkrUAnfrm;IZ^Ni~KT71W7&5-Hֹ^#;Q:5^'[3'ecxWeћdj#ed#YE^^VEMJ&@&"R_7r7kzfϦÔ~)^x۰lEVWھPAJ XCPL!bJ\PH|Tb{X1؂-Y!^UE9%QN ^\(]2vO_UGl8Db4R+ 8eX.*2*qVX9' H&rШ-C ǭb J/b N IB: t)VBRPf!\NbV3%RPLJ6]_< @˅g>q1-fc@\'  p ^J ' lAb7CE#7zU J ^fփR<-(+ǷLW*13ay87^@$L4*HUöYvT bOKvUwB, Y6 ċ`C (X$*'`kq^u48|*+pלo]H b@/zɐG6n0>;yg;~>?ȓ{yόr)sCo³9gGxil6w.qf/Ro9ϫ )Y+Ivm.'5-3\Ns[NZ}+0{6s5 +宮|x$ ~Ǘ32 DwxYN]˾U۳m\NIS`桳28Y!`rYtؑ^~|W;yv;Ol7w]`">?4ܹ( <3NkNxwر$dLض86?j`p﫮ʮ~s!vx蜜˯ƻOpzEΌpgFgAڗs[!:{1e~O^l76ϊ3eWerXΎܱK[soGǃ\JS8yt|4Niw˖J;nY~l*%ssSwyEPDbv`+QkMWVTw]zޥwO"I7hNB4TFS $B0TNJ-XF)/jfhY Z[fJY/tZf@Sy]#;HLmY )]Y5#  endstream endobj 234 0 obj << /Type /Page /Parent 3 0 R /Annots [ 236 0 R 238 0 R 240 0 R 244 0 R 246 0 R 248 0 R 252 0 R 254 0 R 256 0 R ] /Contents 235 0 R >> endobj 235 0 obj << /Length 16353 >> stream q 15.000 24.412 577.500 752.588 re W n 0.965 0.965 0.965 rg 26.250 570.078 555.000 206.922 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 570.078 m 581.250 570.078 l 581.250 570.828 l 26.250 570.828 l f q 35.250 581.328 537.000 195.672 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 1: UCSC Ebola Genome Browser)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Four annotation tracks are displayed. The NCBI Genes track follows a display convention in which coding regions are )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(shown at full height and UTRs at half height. Clicking on an item in this track takes the user to a page of information on the )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(gene. The UniProt/SwissProt Protein Annotations track is shown in dense display mode. Clicking on this track expands it )] TJ ET BT 35.250 706.897 Td /F1 9.8 Tf [(such that individual items, including protein motifs, domains, cleavage sites and other features, are labeled and staggered )] TJ ET BT 35.250 693.161 Td /F1 9.8 Tf [(vertically if they overlap, as is done in the gene track. The B-Cell Epitopes track from IEDB, displayed in dense mode, )] TJ ET BT 35.250 679.425 Td /F1 9.8 Tf [(shows protein regions where antibodies are known to bind. The Multiz Genome Alignments track is configured to show just )] TJ ET BT 35.250 665.689 Td /F1 9.8 Tf [(a printable subset of the available genomes. When zoomed out to view the full genome \(as here\), changes between the )] TJ ET BT 35.250 651.952 Td /F1 9.8 Tf [(reference genome are visible as colored lines: green for synonymous coding changes, red for non-synonymous, blue for )] TJ ET BT 35.250 638.216 Td /F1 9.8 Tf [(UTR changes, and light yellow for missing data. When zoomed in sufficiently, individual amino acid and base differences )] TJ ET BT 35.250 624.480 Td /F1 9.8 Tf [(are shown instead.)] TJ ET Q BT 26.250 553.054 Td /F4 9.8 Tf [(Checking the impact of the Sierra Leone 2014 mutations on an epitope)] TJ ET BT 26.250 533.649 Td /F1 9.8 Tf [(Across various strains of Ebola and various outbreaks dating back to 1976, the crucial GP gene, which is the only one exposed )] TJ ET BT 26.250 521.745 Td /F1 9.8 Tf [(on the surface of the virus, has large regions that are conserved. When combined with the positive results in non-human )] TJ ET BT 26.250 509.840 Td /F1 9.8 Tf [(primate trials, it seems likely that the vaccines now in Phase I trials)] TJ ET 0.267 0.267 0.267 rg BT 313.973 511.347 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 323.610 513.728 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 326.019 511.347 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 335.657 509.840 Td /F1 9.8 Tf [( and previously developed antibodies will be effective )] TJ ET BT 26.250 497.935 Td /F1 9.8 Tf [(across a large range of Ebola viruses.)] TJ ET BT 26.250 478.530 Td /F1 9.8 Tf [(Figure 2 illustrates how one can use the Genome Browser to inspect the degree of variation of a particular antibody epitope )] TJ ET BT 26.250 466.626 Td /F1 9.8 Tf [(sequence in the current outbreak. At the top of the display, the browser shows the region of the Ebola genomic nucleotide )] TJ ET BT 26.250 454.721 Td /F1 9.8 Tf [(reference sequence in view, here zoomed to a 77 bp region. The UniProt track indicates that one is looking at a part of the GP1 )] TJ ET BT 26.250 442.816 Td /F1 9.8 Tf [(protein, in the extracellular, mucin-like region, located next to a CHZ \(histone chaperone\) domain \(shown in the Pfam track\).)] TJ ET 0.965 0.965 0.965 rg 26.250 55.722 555.000 377.213 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 432.935 m 581.250 432.935 l 581.250 432.185 l 26.250 432.185 l f 26.250 55.722 m 581.250 55.722 l 581.250 56.472 l 26.250 56.472 l f q 450.000 0 0 216.750 35.250 206.435 cm /I12 Do Q q 35.250 66.972 537.000 133.463 re W n 0.271 0.267 0.267 rg BT 35.250 190.911 Td /F4 9.8 Tf [(Fig. 2: UCSC Ebola Genome Browser zoomed in to show the epitope of the 4G7 antibody, part of ZMapp, a triple )] TJ ET BT 35.250 179.007 Td /F4 9.8 Tf [(antibody experimental Ebola treatment)] TJ ET BT 35.250 159.637 Td /F1 9.8 Tf [(In this view the NCBI Genes, SwissProt, Pfam, IEDB and PDB annotation tracks have been set to pack display mode, )] TJ ET BT 35.250 145.900 Td /F1 9.8 Tf [(which shows descriptive labels of the individual track features. The Multiz Genome Alignments annotation showing the )] TJ ET BT 35.250 132.164 Td /F1 9.8 Tf [(alignment of other Ebola strain sequences to the reference sequence has been configured by setting the 160 Accessions )] TJ ET BT 35.250 118.428 Td /F1 9.8 Tf [(track to full display mode, which \(at this zoom level\) shows amino acid sequences for each of the strains listed. In this )] TJ ET BT 35.250 104.692 Td /F1 9.8 Tf [(example, the number of displayed strains has been reduced to only one sequence per outbreak by adjusting additional )] TJ ET BT 35.250 90.955 Td /F1 9.8 Tf [(track settings, accessed by clicking on the 160 Accessions track label. The annotation Sites that Carry a Unique Base is )] TJ ET BT 35.250 77.219 Td /F1 9.8 Tf [(displayed by setting the 2014 Specific variation track to pack mode.)] TJ ET Q BT 26.250 38.698 Td /F1 9.8 Tf [(The IEDB track in Figure 2 shows that the protein encoded by the nucleotide sequence in this view is partially targeted by four )] TJ ET Q q 15.000 24.412 577.500 752.588 re W n 0.965 0.965 0.965 rg 26.250 570.078 555.000 206.922 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 570.078 m 581.250 570.078 l 581.250 570.828 l 26.250 570.828 l f q 35.250 581.328 537.000 195.672 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 1: UCSC Ebola Genome Browser)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Four annotation tracks are displayed. The NCBI Genes track follows a display convention in which coding regions are )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(shown at full height and UTRs at half height. Clicking on an item in this track takes the user to a page of information on the )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(gene. The UniProt/SwissProt Protein Annotations track is shown in dense display mode. Clicking on this track expands it )] TJ ET BT 35.250 706.897 Td /F1 9.8 Tf [(such that individual items, including protein motifs, domains, cleavage sites and other features, are labeled and staggered )] TJ ET BT 35.250 693.161 Td /F1 9.8 Tf [(vertically if they overlap, as is done in the gene track. The B-Cell Epitopes track from IEDB, displayed in dense mode, )] TJ ET BT 35.250 679.425 Td /F1 9.8 Tf [(shows protein regions where antibodies are known to bind. The Multiz Genome Alignments track is configured to show just )] TJ ET BT 35.250 665.689 Td /F1 9.8 Tf [(a printable subset of the available genomes. When zoomed out to view the full genome \(as here\), changes between the )] TJ ET BT 35.250 651.952 Td /F1 9.8 Tf [(reference genome are visible as colored lines: green for synonymous coding changes, red for non-synonymous, blue for )] TJ ET BT 35.250 638.216 Td /F1 9.8 Tf [(UTR changes, and light yellow for missing data. When zoomed in sufficiently, individual amino acid and base differences )] TJ ET BT 35.250 624.480 Td /F1 9.8 Tf [(are shown instead.)] TJ ET Q BT 26.250 553.054 Td /F4 9.8 Tf [(Checking the impact of the Sierra Leone 2014 mutations on an epitope)] TJ ET BT 26.250 533.649 Td /F1 9.8 Tf [(Across various strains of Ebola and various outbreaks dating back to 1976, the crucial GP gene, which is the only one exposed )] TJ ET BT 26.250 521.745 Td /F1 9.8 Tf [(on the surface of the virus, has large regions that are conserved. When combined with the positive results in non-human )] TJ ET BT 26.250 509.840 Td /F1 9.8 Tf [(primate trials, it seems likely that the vaccines now in Phase I trials)] TJ ET 0.267 0.267 0.267 rg BT 313.973 511.347 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 323.610 513.728 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 326.019 511.347 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 335.657 509.840 Td /F1 9.8 Tf [( and previously developed antibodies will be effective )] TJ ET BT 26.250 497.935 Td /F1 9.8 Tf [(across a large range of Ebola viruses.)] TJ ET BT 26.250 478.530 Td /F1 9.8 Tf [(Figure 2 illustrates how one can use the Genome Browser to inspect the degree of variation of a particular antibody epitope )] TJ ET BT 26.250 466.626 Td /F1 9.8 Tf [(sequence in the current outbreak. At the top of the display, the browser shows the region of the Ebola genomic nucleotide )] TJ ET BT 26.250 454.721 Td /F1 9.8 Tf [(reference sequence in view, here zoomed to a 77 bp region. The UniProt track indicates that one is looking at a part of the GP1 )] TJ ET BT 26.250 442.816 Td /F1 9.8 Tf [(protein, in the extracellular, mucin-like region, located next to a CHZ \(histone chaperone\) domain \(shown in the Pfam track\).)] TJ ET 0.965 0.965 0.965 rg 26.250 55.722 555.000 377.213 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 432.935 m 581.250 432.935 l 581.250 432.185 l 26.250 432.185 l f 26.250 55.722 m 581.250 55.722 l 581.250 56.472 l 26.250 56.472 l f q 450.000 0 0 216.750 35.250 206.435 cm /I14 Do Q q 35.250 66.972 537.000 133.463 re W n 0.271 0.267 0.267 rg BT 35.250 190.911 Td /F4 9.8 Tf [(Fig. 2: UCSC Ebola Genome Browser zoomed in to show the epitope of the 4G7 antibody, part of ZMapp, a triple )] TJ ET BT 35.250 179.007 Td /F4 9.8 Tf [(antibody experimental Ebola treatment)] TJ ET BT 35.250 159.637 Td /F1 9.8 Tf [(In this view the NCBI Genes, SwissProt, Pfam, IEDB and PDB annotation tracks have been set to pack display mode, )] TJ ET BT 35.250 145.900 Td /F1 9.8 Tf [(which shows descriptive labels of the individual track features. The Multiz Genome Alignments annotation showing the )] TJ ET BT 35.250 132.164 Td /F1 9.8 Tf [(alignment of other Ebola strain sequences to the reference sequence has been configured by setting the 160 Accessions )] TJ ET BT 35.250 118.428 Td /F1 9.8 Tf [(track to full display mode, which \(at this zoom level\) shows amino acid sequences for each of the strains listed. In this )] TJ ET BT 35.250 104.692 Td /F1 9.8 Tf [(example, the number of displayed strains has been reduced to only one sequence per outbreak by adjusting additional )] TJ ET BT 35.250 90.955 Td /F1 9.8 Tf [(track settings, accessed by clicking on the 160 Accessions track label. The annotation Sites that Carry a Unique Base is )] TJ ET BT 35.250 77.219 Td /F1 9.8 Tf [(displayed by setting the 2014 Specific variation track to pack mode.)] TJ ET Q BT 26.250 38.698 Td /F1 9.8 Tf [(The IEDB track in Figure 2 shows that the protein encoded by the nucleotide sequence in this view is partially targeted by four )] TJ ET Q q 15.000 24.412 577.500 752.588 re W n 0.965 0.965 0.965 rg 26.250 570.078 555.000 206.922 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 570.078 m 581.250 570.078 l 581.250 570.828 l 26.250 570.828 l f q 35.250 581.328 537.000 195.672 re W n 0.271 0.267 0.267 rg BT 35.250 767.476 Td /F4 9.8 Tf [(Fig. 1: UCSC Ebola Genome Browser)] TJ ET BT 35.250 748.106 Td /F1 9.8 Tf [(Four annotation tracks are displayed. The NCBI Genes track follows a display convention in which coding regions are )] TJ ET BT 35.250 734.370 Td /F1 9.8 Tf [(shown at full height and UTRs at half height. Clicking on an item in this track takes the user to a page of information on the )] TJ ET BT 35.250 720.634 Td /F1 9.8 Tf [(gene. The UniProt/SwissProt Protein Annotations track is shown in dense display mode. Clicking on this track expands it )] TJ ET BT 35.250 706.897 Td /F1 9.8 Tf [(such that individual items, including protein motifs, domains, cleavage sites and other features, are labeled and staggered )] TJ ET BT 35.250 693.161 Td /F1 9.8 Tf [(vertically if they overlap, as is done in the gene track. The B-Cell Epitopes track from IEDB, displayed in dense mode, )] TJ ET BT 35.250 679.425 Td /F1 9.8 Tf [(shows protein regions where antibodies are known to bind. The Multiz Genome Alignments track is configured to show just )] TJ ET BT 35.250 665.689 Td /F1 9.8 Tf [(a printable subset of the available genomes. When zoomed out to view the full genome \(as here\), changes between the )] TJ ET BT 35.250 651.952 Td /F1 9.8 Tf [(reference genome are visible as colored lines: green for synonymous coding changes, red for non-synonymous, blue for )] TJ ET BT 35.250 638.216 Td /F1 9.8 Tf [(UTR changes, and light yellow for missing data. When zoomed in sufficiently, individual amino acid and base differences )] TJ ET BT 35.250 624.480 Td /F1 9.8 Tf [(are shown instead.)] TJ ET Q BT 26.250 553.054 Td /F4 9.8 Tf [(Checking the impact of the Sierra Leone 2014 mutations on an epitope)] TJ ET BT 26.250 533.649 Td /F1 9.8 Tf [(Across various strains of Ebola and various outbreaks dating back to 1976, the crucial GP gene, which is the only one exposed )] TJ ET BT 26.250 521.745 Td /F1 9.8 Tf [(on the surface of the virus, has large regions that are conserved. When combined with the positive results in non-human )] TJ ET BT 26.250 509.840 Td /F1 9.8 Tf [(primate trials, it seems likely that the vaccines now in Phase I trials)] TJ ET 0.267 0.267 0.267 rg BT 313.973 511.347 Td /F4 8.7 Tf [(15)] TJ ET 0.271 0.267 0.267 rg BT 323.610 513.728 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 326.019 511.347 Td /F4 8.7 Tf [(16)] TJ ET 0.271 0.267 0.267 rg BT 335.657 509.840 Td /F1 9.8 Tf [( and previously developed antibodies will be effective )] TJ ET BT 26.250 497.935 Td /F1 9.8 Tf [(across a large range of Ebola viruses.)] TJ ET BT 26.250 478.530 Td /F1 9.8 Tf [(Figure 2 illustrates how one can use the Genome Browser to inspect the degree of variation of a particular antibody epitope )] TJ ET BT 26.250 466.626 Td /F1 9.8 Tf [(sequence in the current outbreak. At the top of the display, the browser shows the region of the Ebola genomic nucleotide )] TJ ET BT 26.250 454.721 Td /F1 9.8 Tf [(reference sequence in view, here zoomed to a 77 bp region. The UniProt track indicates that one is looking at a part of the GP1 )] TJ ET BT 26.250 442.816 Td /F1 9.8 Tf [(protein, in the extracellular, mucin-like region, located next to a CHZ \(histone chaperone\) domain \(shown in the Pfam track\).)] TJ ET 0.965 0.965 0.965 rg 26.250 55.722 555.000 377.213 re f 0.267 0.267 0.267 rg 0.267 0.267 0.267 RG 26.250 432.935 m 581.250 432.935 l 581.250 432.185 l 26.250 432.185 l f 26.250 55.722 m 581.250 55.722 l 581.250 56.472 l 26.250 56.472 l f q 450.000 0 0 216.750 35.250 206.435 cm /I16 Do Q q 35.250 66.972 537.000 133.463 re W n 0.271 0.267 0.267 rg BT 35.250 190.911 Td /F4 9.8 Tf [(Fig. 2: UCSC Ebola Genome Browser zoomed in to show the epitope of the 4G7 antibody, part of ZMapp, a triple )] TJ ET BT 35.250 179.007 Td /F4 9.8 Tf [(antibody experimental Ebola treatment)] TJ ET BT 35.250 159.637 Td /F1 9.8 Tf [(In this view the NCBI Genes, SwissProt, Pfam, IEDB and PDB annotation tracks have been set to pack display mode, )] TJ ET BT 35.250 145.900 Td /F1 9.8 Tf [(which shows descriptive labels of the individual track features. The Multiz Genome Alignments annotation showing the )] TJ ET BT 35.250 132.164 Td /F1 9.8 Tf [(alignment of other Ebola strain sequences to the reference sequence has been configured by setting the 160 Accessions )] TJ ET BT 35.250 118.428 Td /F1 9.8 Tf [(track to full display mode, which \(at this zoom level\) shows amino acid sequences for each of the strains listed. In this )] TJ ET BT 35.250 104.692 Td /F1 9.8 Tf [(example, the number of displayed strains has been reduced to only one sequence per outbreak by adjusting additional )] TJ ET BT 35.250 90.955 Td /F1 9.8 Tf [(track settings, accessed by clicking on the 160 Accessions track label. The annotation Sites that Carry a Unique Base is )] TJ ET BT 35.250 77.219 Td /F1 9.8 Tf [(displayed by setting the 2014 Specific variation track to pack mode.)] TJ ET Q BT 26.250 38.698 Td /F1 9.8 Tf [(The IEDB track in Figure 2 shows that the protein encoded by the nucleotide sequence in this view is partially targeted by four )] TJ ET Q q 450.000 0 0 216.750 35.250 206.435 cm /I18 Do Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(3)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 236 0 obj << /Type /Annot /Subtype /Link /A 237 0 R /Border [0 0 0] /H /I /Rect [ 313.9725 510.5454 323.6098 519.3637 ] >> endobj 237 0 obj << /Type /Action >> endobj 238 0 obj << /Type /Annot /Subtype /Link /A 239 0 R /Border [0 0 0] /H /I /Rect [ 326.0192 510.5454 335.6565 519.3637 ] >> endobj 239 0 obj << /Type /Action >> endobj 240 0 obj << /Type /Annot /Subtype /Link /A 241 0 R /Border [0 0 0] /H /I /Rect [ 35.2500 206.4352 485.2500 423.1852 ] >> endobj 241 0 obj << /Type /Action /S /URI /URI (http://currents.plos.org/outbreaks/files/2014/10/Fig2.png) >> endobj 242 0 obj << /Type /XObject /Subtype /Image /Width 600 /Height 289 /Filter /FlateDecode /DecodeParms << /Predictor 15 /Colors 1 /Columns 600 /BitsPerComponent 8>> /ColorSpace /DeviceGray /BitsPerComponent 8 /Length 30258>> stream xbk_qH$I$I$I$I$I$I$I#I$I11c1c1Zku]Zkk뺾~9~_}9t{,OT4O8@1E78HcfVIR $A/U@ȁc`SЃ' 1ߨpdZrͱhthaQ(b k!Ku|#EX+90"@#t>ƌ8t5*vR@q $`2:2 D@qI4"b_C0P  IEMJ'T v ,l.)HmBa&kf7EB XeYvsȮT `-jшMtm~ǒLl\"JZopׅM5?Z78:7ux M!%6;UGw̜ݬ<.4ai+S;ްS]iޡ$J\fv|& ~(s`4u+۔bqb}8{BegKI 4LqNV3?DT+i8?,Ǔ2p}H=.i M WA.XQ%\:"pe)LCS/UƤ2I sD *,C%—}'7Yt^%+E#h-d#><,!+;yr#'YsIp"xX:ҎꁹX22XqI,WN|T2lmt}/`Lvy4W `pzבj#Cm؝F7QQDRdw^ڊi'\K?lG:=x!iKOF[I C,ۜ=t`]i-Y860 T8R8/\.}Kd3֭YV!l|)F$˸aQN[m FΝiu*k­xQҿ*-su.*H]HMUF%:JʼnM'.:`馫-_ qk{Ʈg4iCP?ZFkj4]J?S]5ڦG#3sQF+H\ď] ձԭ ,^B#υqyEJVnp畍pS ,XWc-yP3r %N+ Sge@Y,n.`ǍH#KxF Ŝ=5'OuS]Ђgc6to H4 *VK6 UKcϖ~O_SIzP3ԭ ߷Jرb{5hպ}p.{ hc?<nA[- Xv) ld7焊U+tXḩ/;^T95g^IDw%VՑ6X0m݁cusKM!OO$Ԍ!ީ@F3T*\U Pz2p3Z&^)]62HnL$ VMdRA7vTTgp# {9>?TX$c>.]#Fޖ-:X`ɯnԈF*GM,K{08Ğرv.*V z*[I"xvC(*upw({҈Xz }n˼e:Iؙaz"s7|.!Uppa"` *9ɏZ)^gH;3ˣleGw iuB8Uv=&X$Hm]ۨx0aSH><-Qj>!X/Ǖ;l4 ZosUX /K`1EX85gbG,# Ic-X*,;|,qڃxۀo #?+G8riH>&z#nC0-?m%Czҽe]a9^Nti:vXX`o-U-G~&s,W4NcڷP}`׃KRđ]#U=[d*U ZR=HHjHHkˎ m%#r (Q6ie^vȲ`9+bGRZP-@{{b)KўJ)'[,oU)p^[`tCMA|TAx;j? /0X].7ASLSIxY~ҿ,WUaqqIRHu;myj~/H/HuѪISg׃EB ^26X ?T!X?-2aZ/},S`KX, X"'?i|L|,B~Bk`Ց/m ,$XFѷ˖$X~,c  ,s`f4:,K~,^[Iԧ"_E/B5Xx[I/sއ z8p/炅N;Z+`aQ&P3Ur Ӣ:r͏zJ#A^ 0]'\[.#bƼ Y.?Gﴂ4Se;,ל0sՇکr5ӢQĻu /VE#m>J U)RV78xJ, 7KFoi:We@h͟Tba*sC0ӻ/m7sU6Dj9Utz^/:46Zr,w횢n.vMM X\m:q@_4)[nY ?5^OacX[I Xvc0gVhCo[qx N՝2Vgvxh &+` ]Ge1Tb8pڅ +`*c'łFA ,@6dwsw:ͱ'@ AC4(7Xsq{Z8GXsPX0k{s,m1T 6Kܛc Lw9[cߛc(EᖶTt{BINсp$-G[{s,_7LTyTԔߛc96UkZT?rqUR&IOTꍜF$> ݛciTj%|UTXG4*[f98IA D>0)OkvRf(E[oAi ٓw_:۵Q`1VUGم駱HE=SXz{1?},Ng2%PX :Aaٳ̆M/ g(Ծkj$1 yhQRnX6 k&W@*u X}fB8jq;cd_)M` tZI(OI{d~e%lҗ)gvsٔ܅qvZ-ՌʖQ%JTQ#$jڼd0fm[Z&ʽ 8Y`Ҏ,}*XHb3 v-҉{`C7˼_# VXX]N> 0<#ѳԫ`ʠ:cis\.|{G3Ýl{`rI<+}NS1Uzl,U 4Co4G \Kⱪ`Le\a`ۤ^\,,5mc$/4"9%^K6Z寂%ʭ$AMpz#Ăel⪭ƹlwl:r͒a,p 7`XNȁDr) L+`UȵPɊL,O9L,BuW(V!9fɸqâ%R`Ip:դXJZKi!W2Y:Tm2h0gcbbdJ{RJKZWOLQAaGEUVqY35$zk:t+`su,:ETW 8}?ֱ$̪:G%_ cI-ֱԠuRuKXai縿@/-:ױFOױ̏(>,}iK--:,cI$K Nu,󔍀ֱU0PԶ~`8>K'H 1<My3fc@ cALd O*V& t0b"gb'VNhAα*MXƀ`4$6PKz֑t`p'LHn! 着.Z

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1~⸒8Y4M5a"%ɝ ¤ANx)I;)rpMmI_ĕX/XkIK>cw_CCcc#JS3N3C{mjddT($$&[\VXmEy| @ϫ؎7o^+]7ZڥW֙==S{>wd$Ɩk_#޷acطyIe2k `ƌbn,}v${T%nvV֣w7Z"l=N4T@uY5ļ=kۤ[8n]=3twhSɟĘIOb8kٓQKޛȼyc=9I6ر!NGyR:tvNڢ>oFg>de֬w'3 ]ήe$b8^͑|D85!KclH'K/87pojIH *zGu8Lw D\o '>[nB7uop/0ә3,[vq@*Ig~k13_|Me'Z?eJLh Ǐ}tK Zǯ.##'''vf{l:nJǼ?8xlY~Q`̹W]UCT{s{ڞK>StEg>瓷}9Z3[#Z/%)7^gOV3~֎*aX 1)/?ѓՠ4 b^&J19Cy)Thm4BIaE_Oa4nuk9p_q~ÿCY'\J7׵ѦO?ߨ{._Vv(ǚd㸟W˗_/ѧ?ɻI0ΟxbmVlo6Z_hm= QTG}xۗGQ@=~.G'uMIzY5ӌB!c]]812$ua״dYwH+@mQUA wplD`>+XDeHm յũ^zubYVn{4f&$T@fĆ& t ќLoHZDFVxv"Mq*"7/* *"y㇔P}Z%>##yM/ kT2Dn֓hb}k-/HH@3UPш 3qznFMl()5(r OɤݠHiK77HGجI3dQ'tbv.3~S9z9Ÿ; Х-W]r L* N- )4:i4$˕{8T߈Izy'XIhx(ԜӜ/Q74t\d](!$FfYgd+gE:O|m $O"[{ӂW[ ˀ"{ O9YW5N$L"O"FnOQOF4i#,&czbnk,ἥҙ'KB&>Y N4I> endobj 263 0 obj << /Length 25267 >> stream 0.271 0.267 0.267 rg q 15.000 31.021 577.500 745.979 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(previously published antibodies: an unnamed one from a screen \(TGEESA\), 12B5-1-1, 14G7 and 4G7. Detailed information )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(about each of these antibodies can be viewed by clicking on the antibody name in the display. In this instance, the details reveal )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(that 14G7 and 4G7 were first described by Olal et al. \(2012\))] TJ ET 0.267 0.267 0.267 rg BT 284.206 745.174 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 293.843 743.667 Td /F1 9.8 Tf [( and Qiu et al. \(2011\))] TJ ET 0.267 0.267 0.267 rg BT 385.435 745.174 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 395.072 743.667 Td /F1 9.8 Tf [(, respectively. Comparing the IEDB and )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(PDB tracks, note that the 14G7 IEDB feature maps to the same region as the 2y6s feature in the PDB track: a crystal structure )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(of the antibody 14G7 is available in the Protein Data Bank under accession 2y6s. A click on the 2y6s feature in the display will )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(show this structure and a link to the primary citation. Olal et al. note that the most significant residues for 14G7 antibody binding )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(are TIAG. Note that there is no matching PDB track feature for the 4G7 antibody: a crystal structure for that antibody, part of the )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(experimental ZMapp drug)] TJ ET 0.267 0.267 0.267 rg BT 137.332 685.650 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 146.969 684.143 Td /F1 9.8 Tf [(, is not available but one can observe that it is binding the same sequence.)] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(The Multiz Genome Alignments annotation in Figure 2 has been configured to show amino acid sequences, with only one strain )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(sequence from each outbreak displayed: Sierra Leone 2014 \(translation of the reference sequence\), Zaire 07 \(KC242800\), )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(Zaire 76 \(NC_002549\), Bundibugyo 07 \(NC_014373\), Reston 89 \(NC_004161\) and Sudan 76 \(KC545389\). In this annotation, a )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(dot indicates that the amino acid is identical to that of the reference sequence at the same position. As previously shown in this )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(journal)] TJ ET 0.267 0.267 0.267 rg BT 55.510 618.626 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 65.147 621.007 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.556 618.626 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.194 617.119 Td /F1 9.8 Tf [(, the Sierra Leone sequence most resembles the two Zaire sequences. This is supported by rows 2 and 3 in the )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(Multiz Genome Alignment display, which show mostly dots relative to the reference sequence in row 1.)] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(As shown in the bottom annotation in Figure 2, the 2014 outbreak sequence does have a mutation in this region \(C/A\), but the )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(green color of the feature indicates that it is synonymous. Therefore, both the 14G7 and 4G7 \(ZMapp\) antibodies most likely will )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(be effective against the current 2014 strain if they were effective against the original Zaire strain.)] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(This example, which can be repeated with any of the other curated 77 IEDB epitopes in other regions of the virus, shows how )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(one can use the Genome Browser to get a quick overview of available information across various databases and determine )] TJ ET BT 26.250 518.786 Td /F1 9.8 Tf [(whether the data support a given hypothesis. In addition to the data natively displayed in the UCSC Genome Browser, users )] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(can import their own annotation data for display on the reference sequence using the browsers custom track feature \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 494.976 Td /F1 9.8 Tf [(http://genome.ucsc.edu/goldenPath/help/customTrack.html)] TJ ET 0.271 0.267 0.267 rg BT 280.413 494.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 475.572 Td /F4 9.8 Tf [(The UCSC Ebola Genome Portal)] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(We link to the UCSC Ebola Genome Browser from a portal page \()] TJ ET 0.267 0.267 0.267 rg BT 309.644 456.167 Td /F1 9.8 Tf [(http://genome.ucsc.edu/ebolaPortal/)] TJ ET 0.271 0.267 0.267 rg BT 465.731 456.167 Td /F1 9.8 Tf [(\) that contains references )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(to numerous other resources and a collection of sequences for antibodies against Ebola that we are curating in support of )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(vaccine and antiserum developers.)] TJ ET BT 26.250 395.755 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 375.801 Td /F1 9.8 Tf [(Given the exponential growth rate of the virus and the mobility of the human population, the current Ebola virus outbreak may )] TJ ET BT 26.250 363.896 Td /F1 9.8 Tf [(not be not contained until late 2015. Todays research efforts may provide some help in managing this outbreak; therefore, )] TJ ET BT 26.250 351.991 Td /F1 9.8 Tf [(anything that can be done to encourage Ebola research and data-sharing seems prudent. To this end we hope the UCSC Ebola )] TJ ET BT 26.250 340.086 Td /F1 9.8 Tf [(Portal and Genome Browser will be a useful tool for researchers. Suggestions for additional tracks and general feedback may )] TJ ET BT 26.250 328.182 Td /F1 9.8 Tf [(be sent to the UCSC Genome Browser public mailing list at genome@soe.ucsc.edu.)] TJ ET BT 26.250 291.579 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 271.625 Td /F1 9.8 Tf [(We would like to thank the Phil Berman lab at UC Santa Cruz for early feedback on the browser, Pardis Sabeti at the Broad )] TJ ET BT 26.250 259.720 Td /F1 9.8 Tf [(Institute for her guidance in selecting data sets, the Rachel Karchin lab at Johns Hopkins University for their customization work )] TJ ET BT 26.250 247.815 Td /F1 9.8 Tf [(on the MuPIT data in support of this project and Charlotte Kent at the CDC for alerting us to the severity of the epidemic. We )] TJ ET BT 26.250 235.911 Td /F1 9.8 Tf [(would also like to thank the entire staff of the UCSC Genome Browser engineering, QA, and sysadmin teams for their help and )] TJ ET BT 26.250 224.006 Td /F1 9.8 Tf [(support in the rapid release of this browser.)] TJ ET BT 26.250 194.903 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 167.449 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 167.449 Td /F1 9.8 Tf [(Meltzer MI, Atkins CY, Santibanez S, Knust B, Petersen BW, Ervin ED, Nichol ST, Damon IK, Washington ML. Estimating the )] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(future number of cases in the ebola epidemic --- Liberia and Sierra Leone, 2014--2015. MMWR Surveill Summ. 2014 Sep )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(26;63:1-14. PubMed PMID:25254986.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keta S, De Clerck H, )] TJ ET BT 26.250 112.330 Td /F1 9.8 Tf [(Tiffany A, Dominguez G, Loua M, Traor A, Koli M, Malano ER, Heleze E, Bocquin A, Mly S, Raoul H, Caro V, Cadar D, )] TJ ET BT 26.250 100.425 Td /F1 9.8 Tf [(Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gnther S. )] TJ ET BT 26.250 88.521 Td /F1 9.8 Tf [(Emergence of Zaire Ebola Virus Disease in Guinea. N Engl J Med. 2014 Apr 16. PubMed PMID:24738640.)] TJ ET BT 26.250 69.116 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 69.116 Td /F1 9.8 Tf [(Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses )] TJ ET BT 26.250 57.211 Td /F1 9.8 Tf [(LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, )] TJ ET BT 26.250 45.306 Td /F1 9.8 Tf [(Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, )] TJ ET Q q 15.000 31.021 577.500 745.979 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(previously published antibodies: an unnamed one from a screen \(TGEESA\), 12B5-1-1, 14G7 and 4G7. Detailed information )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(about each of these antibodies can be viewed by clicking on the antibody name in the display. In this instance, the details reveal )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(that 14G7 and 4G7 were first described by Olal et al. \(2012\))] TJ ET 0.267 0.267 0.267 rg BT 284.206 745.174 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 293.843 743.667 Td /F1 9.8 Tf [( and Qiu et al. \(2011\))] TJ ET 0.267 0.267 0.267 rg BT 385.435 745.174 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 395.072 743.667 Td /F1 9.8 Tf [(, respectively. Comparing the IEDB and )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(PDB tracks, note that the 14G7 IEDB feature maps to the same region as the 2y6s feature in the PDB track: a crystal structure )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(of the antibody 14G7 is available in the Protein Data Bank under accession 2y6s. A click on the 2y6s feature in the display will )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(show this structure and a link to the primary citation. Olal et al. note that the most significant residues for 14G7 antibody binding )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(are TIAG. Note that there is no matching PDB track feature for the 4G7 antibody: a crystal structure for that antibody, part of the )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(experimental ZMapp drug)] TJ ET 0.267 0.267 0.267 rg BT 137.332 685.650 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 146.969 684.143 Td /F1 9.8 Tf [(, is not available but one can observe that it is binding the same sequence.)] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(The Multiz Genome Alignments annotation in Figure 2 has been configured to show amino acid sequences, with only one strain )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(sequence from each outbreak displayed: Sierra Leone 2014 \(translation of the reference sequence\), Zaire 07 \(KC242800\), )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(Zaire 76 \(NC_002549\), Bundibugyo 07 \(NC_014373\), Reston 89 \(NC_004161\) and Sudan 76 \(KC545389\). In this annotation, a )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(dot indicates that the amino acid is identical to that of the reference sequence at the same position. As previously shown in this )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(journal)] TJ ET 0.267 0.267 0.267 rg BT 55.510 618.626 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 65.147 621.007 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.556 618.626 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.194 617.119 Td /F1 9.8 Tf [(, the Sierra Leone sequence most resembles the two Zaire sequences. This is supported by rows 2 and 3 in the )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(Multiz Genome Alignment display, which show mostly dots relative to the reference sequence in row 1.)] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(As shown in the bottom annotation in Figure 2, the 2014 outbreak sequence does have a mutation in this region \(C/A\), but the )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(green color of the feature indicates that it is synonymous. Therefore, both the 14G7 and 4G7 \(ZMapp\) antibodies most likely will )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(be effective against the current 2014 strain if they were effective against the original Zaire strain.)] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(This example, which can be repeated with any of the other curated 77 IEDB epitopes in other regions of the virus, shows how )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(one can use the Genome Browser to get a quick overview of available information across various databases and determine )] TJ ET BT 26.250 518.786 Td /F1 9.8 Tf [(whether the data support a given hypothesis. In addition to the data natively displayed in the UCSC Genome Browser, users )] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(can import their own annotation data for display on the reference sequence using the browsers custom track feature \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 494.976 Td /F1 9.8 Tf [(http://genome.ucsc.edu/goldenPath/help/customTrack.html)] TJ ET 0.271 0.267 0.267 rg BT 280.413 494.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 475.572 Td /F4 9.8 Tf [(The UCSC Ebola Genome Portal)] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(We link to the UCSC Ebola Genome Browser from a portal page \()] TJ ET 0.267 0.267 0.267 rg BT 309.644 456.167 Td /F1 9.8 Tf [(http://genome.ucsc.edu/ebolaPortal/)] TJ ET 0.271 0.267 0.267 rg BT 465.731 456.167 Td /F1 9.8 Tf [(\) that contains references )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(to numerous other resources and a collection of sequences for antibodies against Ebola that we are curating in support of )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(vaccine and antiserum developers.)] TJ ET BT 26.250 395.755 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 375.801 Td /F1 9.8 Tf [(Given the exponential growth rate of the virus and the mobility of the human population, the current Ebola virus outbreak may )] TJ ET BT 26.250 363.896 Td /F1 9.8 Tf [(not be not contained until late 2015. Todays research efforts may provide some help in managing this outbreak; therefore, )] TJ ET BT 26.250 351.991 Td /F1 9.8 Tf [(anything that can be done to encourage Ebola research and data-sharing seems prudent. To this end we hope the UCSC Ebola )] TJ ET BT 26.250 340.086 Td /F1 9.8 Tf [(Portal and Genome Browser will be a useful tool for researchers. Suggestions for additional tracks and general feedback may )] TJ ET BT 26.250 328.182 Td /F1 9.8 Tf [(be sent to the UCSC Genome Browser public mailing list at genome@soe.ucsc.edu.)] TJ ET BT 26.250 291.579 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 271.625 Td /F1 9.8 Tf [(We would like to thank the Phil Berman lab at UC Santa Cruz for early feedback on the browser, Pardis Sabeti at the Broad )] TJ ET BT 26.250 259.720 Td /F1 9.8 Tf [(Institute for her guidance in selecting data sets, the Rachel Karchin lab at Johns Hopkins University for their customization work )] TJ ET BT 26.250 247.815 Td /F1 9.8 Tf [(on the MuPIT data in support of this project and Charlotte Kent at the CDC for alerting us to the severity of the epidemic. We )] TJ ET BT 26.250 235.911 Td /F1 9.8 Tf [(would also like to thank the entire staff of the UCSC Genome Browser engineering, QA, and sysadmin teams for their help and )] TJ ET BT 26.250 224.006 Td /F1 9.8 Tf [(support in the rapid release of this browser.)] TJ ET BT 26.250 194.903 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 167.449 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 167.449 Td /F1 9.8 Tf [(Meltzer MI, Atkins CY, Santibanez S, Knust B, Petersen BW, Ervin ED, Nichol ST, Damon IK, Washington ML. Estimating the )] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(future number of cases in the ebola epidemic --- Liberia and Sierra Leone, 2014--2015. MMWR Surveill Summ. 2014 Sep )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(26;63:1-14. PubMed PMID:25254986.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keta S, De Clerck H, )] TJ ET BT 26.250 112.330 Td /F1 9.8 Tf [(Tiffany A, Dominguez G, Loua M, Traor A, Koli M, Malano ER, Heleze E, Bocquin A, Mly S, Raoul H, Caro V, Cadar D, )] TJ ET BT 26.250 100.425 Td /F1 9.8 Tf [(Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gnther S. )] TJ ET BT 26.250 88.521 Td /F1 9.8 Tf [(Emergence of Zaire Ebola Virus Disease in Guinea. N Engl J Med. 2014 Apr 16. PubMed PMID:24738640.)] TJ ET BT 26.250 69.116 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 69.116 Td /F1 9.8 Tf [(Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses )] TJ ET BT 26.250 57.211 Td /F1 9.8 Tf [(LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, )] TJ ET BT 26.250 45.306 Td /F1 9.8 Tf [(Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, )] TJ ET Q q 15.000 31.021 577.500 745.979 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(previously published antibodies: an unnamed one from a screen \(TGEESA\), 12B5-1-1, 14G7 and 4G7. Detailed information )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(about each of these antibodies can be viewed by clicking on the antibody name in the display. In this instance, the details reveal )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(that 14G7 and 4G7 were first described by Olal et al. \(2012\))] TJ ET 0.267 0.267 0.267 rg BT 284.206 745.174 Td /F4 8.7 Tf [(17)] TJ ET 0.271 0.267 0.267 rg BT 293.843 743.667 Td /F1 9.8 Tf [( and Qiu et al. \(2011\))] TJ ET 0.267 0.267 0.267 rg BT 385.435 745.174 Td /F4 8.7 Tf [(18)] TJ ET 0.271 0.267 0.267 rg BT 395.072 743.667 Td /F1 9.8 Tf [(, respectively. Comparing the IEDB and )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(PDB tracks, note that the 14G7 IEDB feature maps to the same region as the 2y6s feature in the PDB track: a crystal structure )] TJ ET BT 26.250 719.857 Td /F1 9.8 Tf [(of the antibody 14G7 is available in the Protein Data Bank under accession 2y6s. A click on the 2y6s feature in the display will )] TJ ET BT 26.250 707.952 Td /F1 9.8 Tf [(show this structure and a link to the primary citation. Olal et al. note that the most significant residues for 14G7 antibody binding )] TJ ET BT 26.250 696.048 Td /F1 9.8 Tf [(are TIAG. Note that there is no matching PDB track feature for the 4G7 antibody: a crystal structure for that antibody, part of the )] TJ ET BT 26.250 684.143 Td /F1 9.8 Tf [(experimental ZMapp drug)] TJ ET 0.267 0.267 0.267 rg BT 137.332 685.650 Td /F4 8.7 Tf [(19)] TJ ET 0.271 0.267 0.267 rg BT 146.969 684.143 Td /F1 9.8 Tf [(, is not available but one can observe that it is binding the same sequence.)] TJ ET BT 26.250 664.738 Td /F1 9.8 Tf [(The Multiz Genome Alignments annotation in Figure 2 has been configured to show amino acid sequences, with only one strain )] TJ ET BT 26.250 652.833 Td /F1 9.8 Tf [(sequence from each outbreak displayed: Sierra Leone 2014 \(translation of the reference sequence\), Zaire 07 \(KC242800\), )] TJ ET BT 26.250 640.929 Td /F1 9.8 Tf [(Zaire 76 \(NC_002549\), Bundibugyo 07 \(NC_014373\), Reston 89 \(NC_004161\) and Sudan 76 \(KC545389\). In this annotation, a )] TJ ET BT 26.250 629.024 Td /F1 9.8 Tf [(dot indicates that the amino acid is identical to that of the reference sequence at the same position. As previously shown in this )] TJ ET BT 26.250 617.119 Td /F1 9.8 Tf [(journal)] TJ ET 0.267 0.267 0.267 rg BT 55.510 618.626 Td /F4 8.7 Tf [(20)] TJ ET 0.271 0.267 0.267 rg BT 65.147 621.007 Td /F1 8.7 Tf [(,)] TJ ET 0.267 0.267 0.267 rg BT 67.556 618.626 Td /F4 8.7 Tf [(21)] TJ ET 0.271 0.267 0.267 rg BT 77.194 617.119 Td /F1 9.8 Tf [(, the Sierra Leone sequence most resembles the two Zaire sequences. This is supported by rows 2 and 3 in the )] TJ ET BT 26.250 605.214 Td /F1 9.8 Tf [(Multiz Genome Alignment display, which show mostly dots relative to the reference sequence in row 1.)] TJ ET BT 26.250 585.810 Td /F1 9.8 Tf [(As shown in the bottom annotation in Figure 2, the 2014 outbreak sequence does have a mutation in this region \(C/A\), but the )] TJ ET BT 26.250 573.905 Td /F1 9.8 Tf [(green color of the feature indicates that it is synonymous. Therefore, both the 14G7 and 4G7 \(ZMapp\) antibodies most likely will )] TJ ET BT 26.250 562.000 Td /F1 9.8 Tf [(be effective against the current 2014 strain if they were effective against the original Zaire strain.)] TJ ET BT 26.250 542.595 Td /F1 9.8 Tf [(This example, which can be repeated with any of the other curated 77 IEDB epitopes in other regions of the virus, shows how )] TJ ET BT 26.250 530.691 Td /F1 9.8 Tf [(one can use the Genome Browser to get a quick overview of available information across various databases and determine )] TJ ET BT 26.250 518.786 Td /F1 9.8 Tf [(whether the data support a given hypothesis. In addition to the data natively displayed in the UCSC Genome Browser, users )] TJ ET BT 26.250 506.881 Td /F1 9.8 Tf [(can import their own annotation data for display on the reference sequence using the browsers custom track feature \()] TJ ET 0.267 0.267 0.267 rg BT 26.250 494.976 Td /F1 9.8 Tf [(http://genome.ucsc.edu/goldenPath/help/customTrack.html)] TJ ET 0.271 0.267 0.267 rg BT 280.413 494.976 Td /F1 9.8 Tf [(\).)] TJ ET BT 26.250 475.572 Td /F4 9.8 Tf [(The UCSC Ebola Genome Portal)] TJ ET BT 26.250 456.167 Td /F1 9.8 Tf [(We link to the UCSC Ebola Genome Browser from a portal page \()] TJ ET 0.267 0.267 0.267 rg BT 309.644 456.167 Td /F1 9.8 Tf [(http://genome.ucsc.edu/ebolaPortal/)] TJ ET 0.271 0.267 0.267 rg BT 465.731 456.167 Td /F1 9.8 Tf [(\) that contains references )] TJ ET BT 26.250 444.262 Td /F1 9.8 Tf [(to numerous other resources and a collection of sequences for antibodies against Ebola that we are curating in support of )] TJ ET BT 26.250 432.357 Td /F1 9.8 Tf [(vaccine and antiserum developers.)] TJ ET BT 26.250 395.755 Td /F4 12.0 Tf [(Discussion)] TJ ET BT 26.250 375.801 Td /F1 9.8 Tf [(Given the exponential growth rate of the virus and the mobility of the human population, the current Ebola virus outbreak may )] TJ ET BT 26.250 363.896 Td /F1 9.8 Tf [(not be not contained until late 2015. Todays research efforts may provide some help in managing this outbreak; therefore, )] TJ ET BT 26.250 351.991 Td /F1 9.8 Tf [(anything that can be done to encourage Ebola research and data-sharing seems prudent. To this end we hope the UCSC Ebola )] TJ ET BT 26.250 340.086 Td /F1 9.8 Tf [(Portal and Genome Browser will be a useful tool for researchers. Suggestions for additional tracks and general feedback may )] TJ ET BT 26.250 328.182 Td /F1 9.8 Tf [(be sent to the UCSC Genome Browser public mailing list at genome@soe.ucsc.edu.)] TJ ET BT 26.250 291.579 Td /F4 12.0 Tf [(Acknowledgements)] TJ ET BT 26.250 271.625 Td /F1 9.8 Tf [(We would like to thank the Phil Berman lab at UC Santa Cruz for early feedback on the browser, Pardis Sabeti at the Broad )] TJ ET BT 26.250 259.720 Td /F1 9.8 Tf [(Institute for her guidance in selecting data sets, the Rachel Karchin lab at Johns Hopkins University for their customization work )] TJ ET BT 26.250 247.815 Td /F1 9.8 Tf [(on the MuPIT data in support of this project and Charlotte Kent at the CDC for alerting us to the severity of the epidemic. We )] TJ ET BT 26.250 235.911 Td /F1 9.8 Tf [(would also like to thank the entire staff of the UCSC Genome Browser engineering, QA, and sysadmin teams for their help and )] TJ ET BT 26.250 224.006 Td /F1 9.8 Tf [(support in the rapid release of this browser.)] TJ ET BT 26.250 194.903 Td /F4 12.0 Tf [(References)] TJ ET BT 26.250 167.449 Td /F1 9.8 Tf [(1.)] TJ ET BT 38.132 167.449 Td /F1 9.8 Tf [(Meltzer MI, Atkins CY, Santibanez S, Knust B, Petersen BW, Ervin ED, Nichol ST, Damon IK, Washington ML. Estimating the )] TJ ET BT 26.250 155.544 Td /F1 9.8 Tf [(future number of cases in the ebola epidemic --- Liberia and Sierra Leone, 2014--2015. MMWR Surveill Summ. 2014 Sep )] TJ ET BT 26.250 143.640 Td /F1 9.8 Tf [(26;63:1-14. PubMed PMID:25254986.)] TJ ET BT 26.250 124.235 Td /F1 9.8 Tf [(2.)] TJ ET BT 38.132 124.235 Td /F1 9.8 Tf [(Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keta S, De Clerck H, )] TJ ET BT 26.250 112.330 Td /F1 9.8 Tf [(Tiffany A, Dominguez G, Loua M, Traor A, Koli M, Malano ER, Heleze E, Bocquin A, Mly S, Raoul H, Caro V, Cadar D, )] TJ ET BT 26.250 100.425 Td /F1 9.8 Tf [(Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gnther S. )] TJ ET BT 26.250 88.521 Td /F1 9.8 Tf [(Emergence of Zaire Ebola Virus Disease in Guinea. N Engl J Med. 2014 Apr 16. PubMed PMID:24738640.)] TJ ET BT 26.250 69.116 Td /F1 9.8 Tf [(3.)] TJ ET BT 38.132 69.116 Td /F1 9.8 Tf [(Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses )] TJ ET BT 26.250 57.211 Td /F1 9.8 Tf [(LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, )] TJ ET BT 26.250 45.306 Td /F1 9.8 Tf [(Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, Saffa S, Sellu J, Jalloh AA, )] TJ ET Q q 0.000 0.000 0.000 rg BT 291.710 19.825 Td /F1 11.0 Tf [(4)] TJ ET BT 25.000 19.825 Td /F1 11.0 Tf [(PLOS Currents Outbreaks)] TJ ET Q endstream endobj 264 0 obj << /Type /Annot /Subtype /Link /A 265 0 R /Border [0 0 0] /H /I /Rect [ 284.2058 744.3722 293.8431 753.1905 ] >> endobj 265 0 obj << /Type /Action >> endobj 266 0 obj << /Type /Annot /Subtype /Link /A 267 0 R /Border [0 0 0] /H /I /Rect [ 385.4346 744.3722 395.0719 753.1905 ] >> endobj 267 0 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Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(A, Garry RF, Khan SH, Sabeti PC. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(outbreak. Science. 2014 Sep 12;345\(6202\):1369-72. PubMed PMID:25214632.)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 712.357 Td /F1 9.8 Tf [(UniProt Consortium. Activities at the Universal Protein Resource \(UniProt\). Nucleic Acids Res. 2014 Jan;42\(Database )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(issue\):D191-8. PubMed PMID:24253303.)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 681.048 Td /F1 9.8 Tf [(Kim Y, Ponomarenko J, Zhu Z, Tamang D, Wang P, Greenbaum J, Lundegaard C, Sette A, Lund O, Bourne PE, Nielsen M, )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(Peters B. Immune epitope database analysis resource. Nucleic Acids Res. 2012 Jul;40\(Web Server issue\):W525-30. PubMed )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(PMID:22610854.)] TJ ET BT 26.250 637.833 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 637.833 Td /F1 9.8 Tf [(NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. )] TJ ET BT 26.250 625.929 Td /F1 9.8 Tf [(2014 Jan;42\(Database issue\):D7-17. PubMed PMID:24259429.)] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 606.524 Td /F1 9.8 Tf [(Upton C, Hogg D, Perrin D, Boone M, Harris NL. Viral genome organizer: a system for analyzing complete viral genomes. )] TJ ET BT 26.250 594.619 Td /F1 9.8 Tf [(Virus Res. 2000 Sep;70\(1-2\):55-64. PubMed PMID:11074125.)] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 575.214 Td /F1 9.8 Tf [(Karolchik D, Barber GP, Casper J, Clawson H, Cline MS, Diekhans M, Dreszer TR, Fujita PA, Guruvadoo L, Haeussler M, )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(Harte RA, Heitner S, Hinrichs AS, Learned K, Lee BT, Li CH, Raney BJ, Rhead B, Rosenbloom KR, Sloan CA, Speir ML, Zweig )] TJ ET BT 26.250 551.405 Td /F1 9.8 Tf [(AS, Haussler D, Kuhn RM, Kent WJ. The UCSC Genome Browser database: 2014 update. Nucleic Acids Res. 2014 )] TJ ET BT 26.250 539.500 Td /F1 9.8 Tf [(Jan;42\(Database issue\):D764-70. PubMed PMID:24270787.)] TJ ET BT 26.250 520.095 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 520.095 Td /F1 9.8 Tf [(Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. )] TJ ET BT 26.250 508.191 Td /F1 9.8 Tf [(Genome Res. 2002 Jun;12\(6\):996-1006. PubMed PMID:12045153.)] TJ ET BT 26.250 488.786 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 488.786 Td /F1 9.8 Tf [(Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the )] TJ ET BT 26.250 476.881 Td /F1 9.8 Tf [(mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100\(20\):11484-9. PubMed PMID:14500911.)] TJ ET BT 26.250 457.476 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 457.476 Td /F1 9.8 Tf [(Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. )] TJ ET BT 26.250 445.572 Td /F1 9.8 Tf [(Nucleic Acids Res. 2000 Jan 1;28\(1\):235-42. PubMed PMID:10592235.)] TJ ET BT 26.250 426.167 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 426.167 Td /F1 9.8 Tf [(Eddy SR. A new generation of homology search tools based on probabilistic inference. Genome Inform. 2009 Oct;23\(1\):205-)] TJ ET BT 26.250 414.262 Td /F1 9.8 Tf [(11. PubMed PMID:20180275.)] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 394.857 Td /F1 9.8 Tf [(Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, )] TJ ET BT 26.250 382.953 Td /F1 9.8 Tf [(Sonnhammer EL, Tate J, Punta M. Pfam: the protein families database. Nucleic Acids Res. 2014 Jan;42\(Database issue\):D222-)] TJ ET BT 26.250 371.048 Td /F1 9.8 Tf [(30. PubMed PMID:24288371.)] TJ ET BT 26.250 351.643 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 351.643 Td /F1 9.8 Tf [(Raney BJ, Dreszer TR, Barber GP, Clawson H, Fujita PA, Wang T, Nguyen N, Paten B, Zweig AS, Karolchik D, Kent WJ. )] TJ ET BT 26.250 339.738 Td /F1 9.8 Tf [(Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. Bioinformatics. )] TJ ET BT 26.250 327.834 Td /F1 9.8 Tf [(2014 Apr 1;30\(7\):1003-5. PubMed PMID:24227676.)] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 308.429 Td /F1 9.8 Tf [(Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, )] TJ ET BT 26.250 296.524 Td /F1 9.8 Tf [(Koup RA, Roederer M, Bailer R, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS. A replication defective )] TJ ET BT 26.250 284.619 Td /F1 9.8 Tf [(recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010 Dec )] TJ ET BT 26.250 272.715 Td /F1 9.8 Tf [(16;29\(2\):304-13. PubMed PMID:21034824.)] TJ ET BT 26.250 253.310 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 253.310 Td /F1 9.8 Tf [(Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H. Vesicular stomatitis virus-based Ebola )] TJ ET BT 26.250 241.405 Td /F1 9.8 Tf [(vaccines with improved cross-protective efficacy. J Infect Dis. 2011 Nov;204 Suppl 3:S1066-74. PubMed PMID:21987743.)] TJ ET BT 26.250 222.000 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 222.000 Td /F1 9.8 Tf [(Olal D, Kuehne AI, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO. )] TJ ET BT 26.250 210.096 Td /F1 9.8 Tf [(Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus. J Virol. 2012 )] TJ ET BT 26.250 198.191 Td /F1 9.8 Tf [(Mar;86\(5\):2809-16. PubMed PMID:22171276.)] TJ ET BT 26.250 178.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 178.786 Td /F1 9.8 Tf [(Qiu X, Alimonti JB, Melito PL, Fernando L, Strher U, Jones SM. Characterization of Zaire ebolavirus glycoprotein-specific )] TJ ET BT 26.250 166.881 Td /F1 9.8 Tf [(monoclonal antibodies. Clin Immunol. 2011 Nov;141\(2\):218-27. PubMed PMID:21925951.)] TJ ET BT 26.250 147.477 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 147.477 Td /F1 9.8 Tf [(Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, )] TJ ET BT 26.250 135.572 Td /F1 9.8 Tf [(Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, )] TJ ET BT 26.250 123.667 Td /F1 9.8 Tf [(Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014 )] TJ ET BT 26.250 111.762 Td /F1 9.8 Tf [(Oct 2;514\(7520\):47-53. PubMed PMID:25171469.)] TJ ET BT 26.250 92.358 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 92.358 Td /F1 9.8 Tf [(Calvignac-Spencer S, Schulze JM, Zickmann F, Renard BY. Clock Rooting Further Demonstrates that Guinea 2014 EBOV )] TJ ET BT 26.250 80.453 Td /F1 9.8 Tf [(is a Member of the Zare Lineage. PLoS Curr. 2014 Jun 16;6. PubMed PMID:24987574.)] TJ ET BT 26.250 61.048 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 61.048 Td /F1 9.8 Tf [(Dudas G, Rambaut A. Phylogenetic Analysis of Guinea 2014 EBOV Ebolavirus Outbreak. PLoS Curr. 2014 May 2;6. )] TJ ET BT 26.250 49.143 Td /F1 9.8 Tf [(PubMed PMID:24860690.)] TJ ET Q q 15.000 39.262 577.500 737.738 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(A, Garry RF, Khan SH, Sabeti PC. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(outbreak. Science. 2014 Sep 12;345\(6202\):1369-72. PubMed PMID:25214632.)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 712.357 Td /F1 9.8 Tf [(UniProt Consortium. Activities at the Universal Protein Resource \(UniProt\). Nucleic Acids Res. 2014 Jan;42\(Database )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(issue\):D191-8. PubMed PMID:24253303.)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 681.048 Td /F1 9.8 Tf [(Kim Y, Ponomarenko J, Zhu Z, Tamang D, Wang P, Greenbaum J, Lundegaard C, Sette A, Lund O, Bourne PE, Nielsen M, )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(Peters B. Immune epitope database analysis resource. Nucleic Acids Res. 2012 Jul;40\(Web Server issue\):W525-30. PubMed )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(PMID:22610854.)] TJ ET BT 26.250 637.833 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 637.833 Td /F1 9.8 Tf [(NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. )] TJ ET BT 26.250 625.929 Td /F1 9.8 Tf [(2014 Jan;42\(Database issue\):D7-17. PubMed PMID:24259429.)] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 606.524 Td /F1 9.8 Tf [(Upton C, Hogg D, Perrin D, Boone M, Harris NL. Viral genome organizer: a system for analyzing complete viral genomes. )] TJ ET BT 26.250 594.619 Td /F1 9.8 Tf [(Virus Res. 2000 Sep;70\(1-2\):55-64. PubMed PMID:11074125.)] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 575.214 Td /F1 9.8 Tf [(Karolchik D, Barber GP, Casper J, Clawson H, Cline MS, Diekhans M, Dreszer TR, Fujita PA, Guruvadoo L, Haeussler M, )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(Harte RA, Heitner S, Hinrichs AS, Learned K, Lee BT, Li CH, Raney BJ, Rhead B, Rosenbloom KR, Sloan CA, Speir ML, Zweig )] TJ ET BT 26.250 551.405 Td /F1 9.8 Tf [(AS, Haussler D, Kuhn RM, Kent WJ. The UCSC Genome Browser database: 2014 update. Nucleic Acids Res. 2014 )] TJ ET BT 26.250 539.500 Td /F1 9.8 Tf [(Jan;42\(Database issue\):D764-70. PubMed PMID:24270787.)] TJ ET BT 26.250 520.095 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 520.095 Td /F1 9.8 Tf [(Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. )] TJ ET BT 26.250 508.191 Td /F1 9.8 Tf [(Genome Res. 2002 Jun;12\(6\):996-1006. PubMed PMID:12045153.)] TJ ET BT 26.250 488.786 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 488.786 Td /F1 9.8 Tf [(Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the )] TJ ET BT 26.250 476.881 Td /F1 9.8 Tf [(mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100\(20\):11484-9. PubMed PMID:14500911.)] TJ ET BT 26.250 457.476 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 457.476 Td /F1 9.8 Tf [(Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. )] TJ ET BT 26.250 445.572 Td /F1 9.8 Tf [(Nucleic Acids Res. 2000 Jan 1;28\(1\):235-42. PubMed PMID:10592235.)] TJ ET BT 26.250 426.167 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 426.167 Td /F1 9.8 Tf [(Eddy SR. A new generation of homology search tools based on probabilistic inference. Genome Inform. 2009 Oct;23\(1\):205-)] TJ ET BT 26.250 414.262 Td /F1 9.8 Tf [(11. PubMed PMID:20180275.)] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 394.857 Td /F1 9.8 Tf [(Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, )] TJ ET BT 26.250 382.953 Td /F1 9.8 Tf [(Sonnhammer EL, Tate J, Punta M. Pfam: the protein families database. Nucleic Acids Res. 2014 Jan;42\(Database issue\):D222-)] TJ ET BT 26.250 371.048 Td /F1 9.8 Tf [(30. PubMed PMID:24288371.)] TJ ET BT 26.250 351.643 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 351.643 Td /F1 9.8 Tf [(Raney BJ, Dreszer TR, Barber GP, Clawson H, Fujita PA, Wang T, Nguyen N, Paten B, Zweig AS, Karolchik D, Kent WJ. )] TJ ET BT 26.250 339.738 Td /F1 9.8 Tf [(Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. Bioinformatics. )] TJ ET BT 26.250 327.834 Td /F1 9.8 Tf [(2014 Apr 1;30\(7\):1003-5. PubMed PMID:24227676.)] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 308.429 Td /F1 9.8 Tf [(Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, )] TJ ET BT 26.250 296.524 Td /F1 9.8 Tf [(Koup RA, Roederer M, Bailer R, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS. A replication defective )] TJ ET BT 26.250 284.619 Td /F1 9.8 Tf [(recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010 Dec )] TJ ET BT 26.250 272.715 Td /F1 9.8 Tf [(16;29\(2\):304-13. PubMed PMID:21034824.)] TJ ET BT 26.250 253.310 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 253.310 Td /F1 9.8 Tf [(Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H. Vesicular stomatitis virus-based Ebola )] TJ ET BT 26.250 241.405 Td /F1 9.8 Tf [(vaccines with improved cross-protective efficacy. J Infect Dis. 2011 Nov;204 Suppl 3:S1066-74. PubMed PMID:21987743.)] TJ ET BT 26.250 222.000 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 222.000 Td /F1 9.8 Tf [(Olal D, Kuehne AI, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO. )] TJ ET BT 26.250 210.096 Td /F1 9.8 Tf [(Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus. J Virol. 2012 )] TJ ET BT 26.250 198.191 Td /F1 9.8 Tf [(Mar;86\(5\):2809-16. PubMed PMID:22171276.)] TJ ET BT 26.250 178.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 178.786 Td /F1 9.8 Tf [(Qiu X, Alimonti JB, Melito PL, Fernando L, Strher U, Jones SM. Characterization of Zaire ebolavirus glycoprotein-specific )] TJ ET BT 26.250 166.881 Td /F1 9.8 Tf [(monoclonal antibodies. Clin Immunol. 2011 Nov;141\(2\):218-27. PubMed PMID:21925951.)] TJ ET BT 26.250 147.477 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 147.477 Td /F1 9.8 Tf [(Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, )] TJ ET BT 26.250 135.572 Td /F1 9.8 Tf [(Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, )] TJ ET BT 26.250 123.667 Td /F1 9.8 Tf [(Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014 )] TJ ET BT 26.250 111.762 Td /F1 9.8 Tf [(Oct 2;514\(7520\):47-53. PubMed PMID:25171469.)] TJ ET BT 26.250 92.358 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 92.358 Td /F1 9.8 Tf [(Calvignac-Spencer S, Schulze JM, Zickmann F, Renard BY. Clock Rooting Further Demonstrates that Guinea 2014 EBOV )] TJ ET BT 26.250 80.453 Td /F1 9.8 Tf [(is a Member of the Zare Lineage. PLoS Curr. 2014 Jun 16;6. PubMed PMID:24987574.)] TJ ET BT 26.250 61.048 Td /F1 9.8 Tf [(21.)] TJ ET BT 43.553 61.048 Td /F1 9.8 Tf [(Dudas G, Rambaut A. Phylogenetic Analysis of Guinea 2014 EBOV Ebolavirus Outbreak. PLoS Curr. 2014 May 2;6. )] TJ ET BT 26.250 49.143 Td /F1 9.8 Tf [(PubMed PMID:24860690.)] TJ ET Q q 15.000 39.262 577.500 737.738 re W n 0.271 0.267 0.267 rg BT 26.250 767.476 Td /F1 9.8 Tf [(Kovoma A, Koninga J, Mustapha I, Kargbo K, Foday M, Yillah M, Kanneh F, Robert W, Massally JL, Chapman SB, Bochicchio )] TJ ET BT 26.250 755.571 Td /F1 9.8 Tf [(J, Murphy C, Nusbaum C, Young S, Birren BW, Grant DS, Scheiffelin JS, Lander ES, Happi C, Gevao SM, Gnirke A, Rambaut )] TJ ET BT 26.250 743.667 Td /F1 9.8 Tf [(A, Garry RF, Khan SH, Sabeti PC. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 )] TJ ET BT 26.250 731.762 Td /F1 9.8 Tf [(outbreak. Science. 2014 Sep 12;345\(6202\):1369-72. PubMed PMID:25214632.)] TJ ET BT 26.250 712.357 Td /F1 9.8 Tf [(4.)] TJ ET BT 38.132 712.357 Td /F1 9.8 Tf [(UniProt Consortium. Activities at the Universal Protein Resource \(UniProt\). Nucleic Acids Res. 2014 Jan;42\(Database )] TJ ET BT 26.250 700.452 Td /F1 9.8 Tf [(issue\):D191-8. PubMed PMID:24253303.)] TJ ET BT 26.250 681.048 Td /F1 9.8 Tf [(5.)] TJ ET BT 38.132 681.048 Td /F1 9.8 Tf [(Kim Y, Ponomarenko J, Zhu Z, Tamang D, Wang P, Greenbaum J, Lundegaard C, Sette A, Lund O, Bourne PE, Nielsen M, )] TJ ET BT 26.250 669.143 Td /F1 9.8 Tf [(Peters B. Immune epitope database analysis resource. Nucleic Acids Res. 2012 Jul;40\(Web Server issue\):W525-30. PubMed )] TJ ET BT 26.250 657.238 Td /F1 9.8 Tf [(PMID:22610854.)] TJ ET BT 26.250 637.833 Td /F1 9.8 Tf [(6.)] TJ ET BT 38.132 637.833 Td /F1 9.8 Tf [(NCBI Resource Coordinators. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. )] TJ ET BT 26.250 625.929 Td /F1 9.8 Tf [(2014 Jan;42\(Database issue\):D7-17. PubMed PMID:24259429.)] TJ ET BT 26.250 606.524 Td /F1 9.8 Tf [(7.)] TJ ET BT 38.132 606.524 Td /F1 9.8 Tf [(Upton C, Hogg D, Perrin D, Boone M, Harris NL. Viral genome organizer: a system for analyzing complete viral genomes. )] TJ ET BT 26.250 594.619 Td /F1 9.8 Tf [(Virus Res. 2000 Sep;70\(1-2\):55-64. PubMed PMID:11074125.)] TJ ET BT 26.250 575.214 Td /F1 9.8 Tf [(8.)] TJ ET BT 38.132 575.214 Td /F1 9.8 Tf [(Karolchik D, Barber GP, Casper J, Clawson H, Cline MS, Diekhans M, Dreszer TR, Fujita PA, Guruvadoo L, Haeussler M, )] TJ ET BT 26.250 563.310 Td /F1 9.8 Tf [(Harte RA, Heitner S, Hinrichs AS, Learned K, Lee BT, Li CH, Raney BJ, Rhead B, Rosenbloom KR, Sloan CA, Speir ML, Zweig )] TJ ET BT 26.250 551.405 Td /F1 9.8 Tf [(AS, Haussler D, Kuhn RM, Kent WJ. The UCSC Genome Browser database: 2014 update. Nucleic Acids Res. 2014 )] TJ ET BT 26.250 539.500 Td /F1 9.8 Tf [(Jan;42\(Database issue\):D764-70. PubMed PMID:24270787.)] TJ ET BT 26.250 520.095 Td /F1 9.8 Tf [(9.)] TJ ET BT 38.132 520.095 Td /F1 9.8 Tf [(Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. )] TJ ET BT 26.250 508.191 Td /F1 9.8 Tf [(Genome Res. 2002 Jun;12\(6\):996-1006. PubMed PMID:12045153.)] TJ ET BT 26.250 488.786 Td /F1 9.8 Tf [(10.)] TJ ET BT 43.553 488.786 Td /F1 9.8 Tf [(Kent WJ, Baertsch R, Hinrichs A, Miller W, Haussler D. Evolution's cauldron: duplication, deletion, and rearrangement in the )] TJ ET BT 26.250 476.881 Td /F1 9.8 Tf [(mouse and human genomes. Proc Natl Acad Sci U S A. 2003 Sep 30;100\(20\):11484-9. PubMed PMID:14500911.)] TJ ET BT 26.250 457.476 Td /F1 9.8 Tf [(11.)] TJ ET BT 43.553 457.476 Td /F1 9.8 Tf [(Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. )] TJ ET BT 26.250 445.572 Td /F1 9.8 Tf [(Nucleic Acids Res. 2000 Jan 1;28\(1\):235-42. PubMed PMID:10592235.)] TJ ET BT 26.250 426.167 Td /F1 9.8 Tf [(12.)] TJ ET BT 43.553 426.167 Td /F1 9.8 Tf [(Eddy SR. A new generation of homology search tools based on probabilistic inference. Genome Inform. 2009 Oct;23\(1\):205-)] TJ ET BT 26.250 414.262 Td /F1 9.8 Tf [(11. PubMed PMID:20180275.)] TJ ET BT 26.250 394.857 Td /F1 9.8 Tf [(13.)] TJ ET BT 43.553 394.857 Td /F1 9.8 Tf [(Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, )] TJ ET BT 26.250 382.953 Td /F1 9.8 Tf [(Sonnhammer EL, Tate J, Punta M. Pfam: the protein families database. Nucleic Acids Res. 2014 Jan;42\(Database issue\):D222-)] TJ ET BT 26.250 371.048 Td /F1 9.8 Tf [(30. PubMed PMID:24288371.)] TJ ET BT 26.250 351.643 Td /F1 9.8 Tf [(14.)] TJ ET BT 43.553 351.643 Td /F1 9.8 Tf [(Raney BJ, Dreszer TR, Barber GP, Clawson H, Fujita PA, Wang T, Nguyen N, Paten B, Zweig AS, Karolchik D, Kent WJ. )] TJ ET BT 26.250 339.738 Td /F1 9.8 Tf [(Track data hubs enable visualization of user-defined genome-wide annotations on the UCSC Genome Browser. Bioinformatics. )] TJ ET BT 26.250 327.834 Td /F1 9.8 Tf [(2014 Apr 1;30\(7\):1003-5. PubMed PMID:24227676.)] TJ ET BT 26.250 308.429 Td /F1 9.8 Tf [(15.)] TJ ET BT 43.553 308.429 Td /F1 9.8 Tf [(Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, )] TJ ET BT 26.250 296.524 Td /F1 9.8 Tf [(Koup RA, Roederer M, Bailer R, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS. A replication defective )] TJ ET BT 26.250 284.619 Td /F1 9.8 Tf [(recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010 Dec )] TJ ET BT 26.250 272.715 Td /F1 9.8 Tf [(16;29\(2\):304-13. PubMed PMID:21034824.)] TJ ET BT 26.250 253.310 Td /F1 9.8 Tf [(16.)] TJ ET BT 43.553 253.310 Td /F1 9.8 Tf [(Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H. Vesicular stomatitis virus-based Ebola )] TJ ET BT 26.250 241.405 Td /F1 9.8 Tf [(vaccines with improved cross-protective efficacy. J Infect Dis. 2011 Nov;204 Suppl 3:S1066-74. PubMed PMID:21987743.)] TJ ET BT 26.250 222.000 Td /F1 9.8 Tf [(17.)] TJ ET BT 43.553 222.000 Td /F1 9.8 Tf [(Olal D, Kuehne AI, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO. )] TJ ET BT 26.250 210.096 Td /F1 9.8 Tf [(Structure of an antibody in complex with its mucin domain linear epitope that is protective against Ebola virus. J Virol. 2012 )] TJ ET BT 26.250 198.191 Td /F1 9.8 Tf [(Mar;86\(5\):2809-16. PubMed PMID:22171276.)] TJ ET BT 26.250 178.786 Td /F1 9.8 Tf [(18.)] TJ ET BT 43.553 178.786 Td /F1 9.8 Tf [(Qiu X, Alimonti JB, Melito PL, Fernando L, Strher U, Jones SM. Characterization of Zaire ebolavirus glycoprotein-specific )] TJ ET BT 26.250 166.881 Td /F1 9.8 Tf [(monoclonal antibodies. Clin Immunol. 2011 Nov;141\(2\):218-27. PubMed PMID:21925951.)] TJ ET BT 26.250 147.477 Td /F1 9.8 Tf [(19.)] TJ ET BT 43.553 147.477 Td /F1 9.8 Tf [(Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A, )] TJ ET BT 26.250 135.572 Td /F1 9.8 Tf [(Morton J, Swope K, Bohorov O, Bohorova N, Goodman C, Kim D, Pauly MH, Velasco J, Pettitt J, Olinger GG, Whaley K, Xu B, )] TJ ET BT 26.250 123.667 Td /F1 9.8 Tf [(Strong JE, Zeitlin L, Kobinger GP. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014 )] TJ ET BT 26.250 111.762 Td /F1 9.8 Tf [(Oct 2;514\(7520\):47-53. PubMed PMID:25171469.)] TJ ET BT 26.250 92.358 Td /F1 9.8 Tf [(20.)] TJ ET BT 43.553 92.358 Td /F1 9.8 Tf [(Calvignac-Spencer S, Schulze JM, Zickmann F, Renard BY. Clock Rooting Further Demonstrates that Guinea 2014 EBOV )] TJ ET BT 26.250 80.453 Td /F1 9.8 Tf [(is a Member of the Zare Lineage. PLoS Curr. 2014 Jun 16;6. 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