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      The UCSC Genome Browser database: 2017 update

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          Abstract

          Since its 2001 debut, the University of California, Santa Cruz (UCSC) Genome Browser ( http://genome.ucsc.edu/) team has provided continuous support to the international genomics and biomedical communities through a web-based, open source platform designed for the fast, scalable display of sequence alignments and annotations landscaped against a vast collection of quality reference genome assemblies. The browser's publicly accessible databases are the backbone of a rich, integrated bioinformatics tool suite that includes a graphical interface for data queries and downloads, alignment programs, command-line utilities and more. This year's highlights include newly designed home and gateway pages; a new ‘multi-region’ track display configuration for exon-only, gene-only and custom regions visualization; new genome browsers for three species (brown kiwi, crab-eating macaque and Malayan flying lemur); eight updated genome assemblies; extended support for new data types such as CRAM, RNA-seq expression data and long-range chromatin interaction pairs; and the unveiling of a new supported mirror site in Japan.

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          Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR

          Maximilian Haeussler, Kai Schönig, Hélène Eckert … (2016)
          Background The success of the CRISPR/Cas9 genome editing technique depends on the choice of the guide RNA sequence, which is facilitated by various websites. Despite the importance and popularity of these algorithms, it is unclear to which extent their predictions are in agreement with actual measurements. Results We conduct the first independent evaluation of CRISPR/Cas9 predictions. To this end, we collect data from eight SpCas9 off-target studies and compare them with the sites predicted by popular algorithms. We identify problems in one implementation but found that sequence-based off-target predictions are very reliable, identifying most off-targets with mutation rates superior to 0.1 %, while the number of false positives can be largely reduced with a cutoff on the off-target score. We also evaluate on-target efficiency prediction algorithms against available datasets. The correlation between the predictions and the guide activity varied considerably, especially for zebrafish. Together with novel data from our labs, we find that the optimal on-target efficiency prediction model strongly depends on whether the guide RNA is expressed from a U6 promoter or transcribed in vitro. We further demonstrate that the best predictions can significantly reduce the time spent on guide screening. Conclusions To make these guidelines easily accessible to anyone planning a CRISPR genome editing experiment, we built a new website (http://crispor.org) that predicts off-targets and helps select and clone efficient guide sequences for more than 120 genomes using different Cas9 proteins and the eight efficiency scoring systems evaluated here. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1012-2) contains supplementary material, which is available to authorized users.
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            The genome of the Western clawed frog Xenopus tropicalis.

            Uffe Hellsten, Richard M. Harland, Michael Gilchrist … (2010)
            The western clawed frog Xenopus tropicalis is an important model for vertebrate development that combines experimental advantages of the African clawed frog Xenopus laevis with more tractable genetics. Here we present a draft genome sequence assembly of X. tropicalis. This genome encodes more than 20,000 protein-coding genes, including orthologs of at least 1700 human disease genes. Over 1 million expressed sequence tags validated the annotation. More than one-third of the genome consists of transposable elements, with unusually prevalent DNA transposons. Like that of other tetrapods, the genome of X. tropicalis contains gene deserts enriched for conserved noncoding elements. The genome exhibits substantial shared synteny with human and chicken over major parts of large chromosomes, broken by lineage-specific chromosome fusions and fissions, mainly in the mammalian lineage.
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              Insights into hominid evolution from the gorilla genome sequence

              Aylwyn Scally, Julien Y Dutheil, LaDeana Hillier … (2012)
              Summary Gorillas are humans’ closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago (Mya). In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nucleic Acids Res
                Journal ID (iso-abbrev): Nucleic Acids Res
                Journal ID (hwp): nar
                Journal ID (publisher-id): nar
                Title: Nucleic Acids Research
                Publisher: Oxford University Press
                ISSN (Print): 0305-1048
                ISSN (Electronic): 1362-4962
                Publication date (Print): 04 January 2017
                Publication date (Electronic): 28 November 2016
                Publication date PMC-release: 28 November 2016
                Volume: 45
                Issue: Database issue , Database issue
                Pages: D626-D634
                Affiliations
                [1 ]Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA
                [2 ]Emory University School of Medicine, Atlanta, GA 30322, USA
                [3 ]Howard Hughes Medical Institute, University of California Santa Cruz, CA 95064, USA
                Author notes
                [* ]To whom correspondence should be addressed. Tel: +1 831 459 3597; Email: cath@ 123456ucsc.edu
                Author information
                http://orcid.org/0000-0001-6382-9738
                http://orcid.org/0000-0001-6382-9738
                Article
                DOI: 10.1093/nar/gkw1134
                PMC ID: 5210591
                PubMed ID: 27899642
                SO-VID: 8a0941c1-06ed-4755-ab70-d7cf1143c9f5
                Copyright © © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date accepted : 31 October 2016
                Date revision received : 17 October 2016
                Date received : 14 September 2016
                Page count
                Pages: 9
                Categories
                Subject: Database Issue
                Custom metadata
                cover-date 04 January 2017

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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