Visual analytics for genomic variants in Jalview 2.11. Jim Procter, U. Dundee Computational biology Mini Symposium 2019
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This document discusses visual analytics tools for genomic variants and the Jalview 2.11 software. It provides an overview of Jalview's capabilities for identifying mutations, highlighting insights through visualization, and its minimal ink approach. Key features discussed include linked views, sequence annotation, structure visualization, and variant analysis functions in the new version. Usage statistics show growing adoption of Jalview since its origins in the late 1990s.
Visual analytics for genomic variants in Jalview 2.11. Jim Procter, U. Dundee Computational biology Mini Symposium 2019
- 1. Visual analytics for genomic variants and Jalview 2.11 Jim Procter Jalview Coordinator @foreveremain orcid://0000-0002-7865-7382 www.compbio.dundee.ac.uk/people.html#jim
- 2. Ceci n’est pas une séquence
- 3. MGGGWGGFNATGGG- NH2 end CO2H end
- 5. Visual Analytics for Sequence Alignments
- 7. Design study methodology:de?nitions X INFORMATIONLOCATION computerhead TASKCLARITYfuzzycrisp NOTENOUGHDATA DESIGN STUDY METHODOLOGY SUITABLE ALGORITHM AUTOMATION POSSIBLE Tamara Munzner Interactive Visualisation Design
- 10. MGGGWGGFNATGGG MGGGWAGFNATGGG MGGGWGVFNATCGG MGGGWAGFNATGGG MGGGWGVFNATCGG MCGGWCPFPATGQG Analytics - Identify mutations Visualisation - Highlight insight - Minimal Ink
- 11. One alignment, many views Sequence features highlight key regions like functional sites Alignment annotation area shows graphs and symbols from calculations and manual curation
- 12. Linked tree viewer allows subgroups to be identified in alignment Group selections Colours and mouseovers Linked Jmol viewer shows one or more structures coloured by alignment views
- 13. 狠狠撸r controls shading in poorly conserved columns Overview locates visible region in alignment Tree (built or imported) allows sub-families to be identified
- 14. Subfamily shading reveals distinct conservation patterns Clicking in tree subdivides alignment Group Consensus lines visualize variation in each subgroup Sequences grouped according to tree
- 15. Peter Troshin (JABAWS) Lauren Liu (RNA SS) Jan Engelhart (VARNA) Michele Clamp James Cuff Steve Searle Andrew Waterhouse Jim Procter David Martin Suzanne Duce Tochukwu (Charles) Ofoegbu Mungo Carstairs Ben Soares Kira Mour?o 1996 – MCView 1997 – Jalview 1 Oxford, EMBL-EBI Standalone/Applet 2005 - Jalview 2 University of Dundee Desktop Application JalviewLite Applet 2019 Jalview 2.11 Desktop Application Jalview: The story so far…
- 26. The Dundee Resource For Protein Structure Prediction and Sequence Analysis ? Web based ? Applications & APIs All at www.compbio.dundee.ac.uk Stuart MacGowan
- 28. New In 2.11!
- 33. Lineage Sorting and Speciation Neutral coalescence running in a species tree Leliaert et al. (2014) Eur. J. Phycol. 49: 179-196 https://frederikleliaert.files.wordpress.com/2014/02/fig5.jpg
- 34. Population biology: Where genomics meets ecology. ? Analysis of variation across ‘Complete’ genome => Epistatic variation ? correlation of polymorphisms at multiple sites ? Gene dynamics, pangenomes, Comparative genomics. ? Understanding evolutionary response to environmental changes ? Selection leads to adaptation and speciation ? Variants also indicate lineage
- 35. Clinical sequencing: The sharp end of variant analysis ? Studies estimate enrichment of variants in cells/patients/pathogens ? Associate with pathology ? Indicate potential for therapy ? Statistical rigor ? Dissection of phenotype ? MoA often left to discussion ? The hard part – relies on accessible evidence ? Interaction effects ? Structural data ? Predicted impact on function
- 36. Observing genetic variation https://commons.wikimedia.org/wiki/Fi le:DNA- Sequencers_from_Flickr_57080968.jpg Sequencers Aligner + Variant Call Pipeline Sample Population
- 37. Observing genetic variation https://commons.wikimedia.org/wiki/Fi le:DNA- Sequencers_from_Flickr_57080968.jpg Sequencers Aligner + Variant Call Pipeline Sample Population VCF File
- 38. Raw reads Assemble / Map to Reference Call Variants Interpret loci Comparative Analysis Structure Function Homology Evolution Interactive Editing Visuali zation Alignments Structures Features Annotation Tree s Sequences PCA Jalview is designed for gene-centric analysis
- 39. ‘Split Frame’ cDNA & Protein MSAs Opened with any linked cDNA/Protein data e.g. ? ENA records ? Flat file ? cDNA translation ? Ensembl Product cDNA/Protein Alignment Reconstruction: ? Gaps inserted according to ‘reference alignment’ Layout and display are configurable.
- 40. Protein sequence -> 3D Structure Future Goal – switch to new EMBL-EBI PDBe SIFTS REST API
- 41. jmol.sourceforge.net Integrated with Jalview 3D Structure Visualization in the Jalview Desktop www.rbvi.ucsf.edu Communication via REST API
- 42. Chimera selection highlighting Selection highlighted in Jalview Press B to select columns!Selection in chimera
- 43. Variant data import in Jalview 2.10 ? Ensembl ? Reference genomes ? Transcripts ? Protein products ? All import from Ensembl REST API via GFF3 ? Sequence variants Includes CLINVAR annotation ? Optimizations for interactive performance when viewing loci
- 45. Jalview 2.10.2: Scripting to count variants Feature Counter Script - Count features in each column Customised: - sequence_variants with Clinical Significance
- 46. Human Homogentisate 1-2, dioxygenase PDB ID 1eyp. Sites with pathogenic variants in red UCSF CHIMERA Variants coloured red 1. Jalview Scripting interface used to create ‘Pathogenic variant’ track. 2. Annotation filter to hide columns. => Shaded grey in structure.
- 47. 2.9 CDS+Protein view Chimera Free Text Queries 2.10 Ensembl+Variants GFF3 CDS SIFTS & mmCIF Scriptable MSA Calcs Less Memory Mungo & Kira’s ‘go faster’ release Data Import Rendering Efficiency SIFTS bug fixes Structure Chooser++ Faster hidden columns Faster PCA & Trees (even) Less Memory Custom score models Occupancy (gap) count Improved Overview Chimera Annotation exchange Bug fixes and Service client Updates for 2.10.x 2.10.5 2014-2018
- 48. 2.11 - VCF import Challenges 1. Map chromosomal coordinates to aligned sequences 2. Visualise and Filter on variant attributes
- 49. New! VCF, .tbi, .fai files are read (using the htsjdk library) for variants overlapping the retrieved sequences. Jalview maps between VCF (GRCh37) and Ensembl (GRCh38). Indexed gnomAD dataset
- 50. Gene variants as generic SO term ‘sequence_variant’ Transcript variants have specific SO terms (VEP consequence) Configure feature display in Jalview Colour…
- 51. Colour variants by their annotation Filter…
- 52. Filter by variant annotation
- 53. Explore variants Tooltip shows filtered attributes Feature Details panel gives allelic information
- 54. The Jalview Desktop Application VARNA RNA 2D Structure Viewer Jmol 3D Molecular Graphics
- 55. 0 5000 10000 15000 20000 25000 30000 35000 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Launches Per Month Average (Last 12m) Unique IPs ● ●● ●● ● ●●●●● ● Jan’14 Java security update Apr’15 Chrome disables Java 2.5 2.6 2.7 2.8 2.9 2.102.8.2 .5 2013 290,917 55,859 2014 257,174 53,999 2015 239,563 52,322 2016 244,351 56,289 2017 249,344 57,386 2018 305,708 77,780 .4.3.2 Month and Yearly Usage Statistics Rollout Of Java 9,10,11
- 56. JavascriptAPI Jalview was available in two flavours JNLP with command line args Java Webstart JNLP File
- 57. Launching Jalview is not always fun…
- 58. Oracle updates Java to fix security exploits already in the wild, but safety is not guaranteed Dieter Bohn on January 13, 2013 07:00 pm http://www.theverge.com/2013/1/13/3873592/oracle-updates-java-security-exploits-in-the-wild
- 60. Lines of code committed to Jalview 2 – since 2004 900,000 800,000 700,000 600,000 500,000 400,000 300,000 200,000 100,000 2.11 commits 2004 2006 2008 2010 2012 2014 2016 2018 2020
- 61. Installing Jalview 2.11 ? Windows and OSX installer ? Linux: .deb, RPM ? Unix: .sh, tar.gz Download at: http://www.jalview.org/getdown/release/1.8/install4j
- 62. Peter Troshin (JABAWS) Lauren Liu (RNA SS) Jan Engelhart (VARNA) Michele Clamp James Cuff Steve Searle Andrew Waterhouse Jim Procter David Martin Suzanne Duce Tochukwu (Charles) Ofoegbu Mungo Carstairs Ben Soares Kira Mour?o 1996 – MCView 1997 – Jalview 1 Oxford, EMBL-EBI Standalone/Applet 2005 - Jalview 2 University of Dundee Desktop Application JalviewLite Applet 2019 Jalview 2.11 Desktop Application Jalview: The story so far… Web based JalviewJS One Codebase
- 63. Requirements for Jalview Native Packages From 2018 SAB Teleconference ? Install once. Works forever. ? No issues with ‘out of date’ certificates ? Over the air update ? Switch between release and dev. Builds ? Configuration management ? Script and Plugin Directories ? Profiles (e.g. command line vs interactive settings) ? Foundation for ‘Jalview as server’ ? Web browser ‘Helper’ application ? Jupyter component ? ? Only need to sign the native platform App that runs Launcher ? Push updates without manual intervention ? getdown release channels ? ‘.JVL’ launch file ? Change the current ‘channel’ ? Pass arguments to Jalvew app
- 64. Lines of code committed to Jalview 2 – since 2004 900,000 800,000 700,000 600,000 500,000 400,000 300,000 200,000 100,000
- 65. June 29th 2018 First time JalviewJS was able to show a Tree and sub-grouped Alignment view. Try it Here!
- 66. JavascriptAPI The Jalview Desktop will come in two flavours: Launch JalviewJS Install Jalview Desktop The JalviewJS Desktop Will need to: - replace JABAWS with Slivka-bio - port/replace HTS-JDK for VCF import
- 67. Launching Jalview from web sites www.jalview.org/services/launchApp ? Version=2.11 ? View JPred4 Result In Desktop ? Version=JalviewJS ? View JPred4 Result In JalviewJS Desktop