HGVS 2015 poster: hgvs, uta, variantanalyzer
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The hgvs and UTA tools provide a Python package (hgvs) and database (UTA) to facilitate working with sequence variants using HGVS nomenclature. hgvs allows parsing, mapping between genome and transcript coordinates, validating, and normalizing variant descriptions. UTA stores versioned transcript and genomic alignments to enable accurate coordinate mapping, including when transcripts differ from genomes due to indels. Together these tools address the need for freely available and well-managed resources for working with variants described using HGVS.
HGVS 2015 poster: hgvs, uta, variantanalyzer
- 1. hgvs and uta: Practical tools for manipulating sequence variants Reece Hart1 , Tim Chiu1 , Vincent A Fusaro1 , John Garcia1 , Kevin B Jacobs2 , Geoffrey B Nilsen1 , Veena Rajaraman1 , Meng Wang3 1 Invitae, 475 Brannan St, San Francisco, CA 941107 2 23andMe, 899 W Evelyn Ave, Mountain View, CA 941041 3 Peking University, 5 Yiheyuan Rd, Haidian, Beijing, China [email protected] Abstract The widespread use of HGVS recommendations to report and share sequence variants highlights the need for freely-available software libraries and readily- accessible, well-managed transcript definitions. We developed two complementary tools, hgvs and UTA, that facilitate the use of HGVS variant nomenclature for literature mining, clinical reporting, and data aggregation. The tools are released under the Apache open source license and available for local installation. UTA Universal Transcript Archive hgvs Python package NCBI CLINVITAE Variant2PubmedReporting hgvsWeb UCSC Ensembl Show me the code! (Stephen Hawking once joked that every formula in a Brief History of Time would halve his readership. Let's hope this doesn't apply to code examples on posters!) Installation: $ pip install hgvs Well, that was easy. (See docs for details and local UTA installation.) Variants are identified in and computed on using genome coordinates Variants are communicated and interpreted using transcript coordinates genome to transcript (g. to c./n.) transcript to genome (c./n. to g.) exon alignments NM_01234.4 NC_000012.3 0 50= NM_01234.4 NC_000012.3 1 100=3I49= NM_01234.4 NC_000012.3 2 5=1I44= transcript NM_01234.4 NM_01234.4 NM_01234.5 NM_01234.5 NM_01234.5 NM_01234.5 ENST012345 ENST012345 reference NM_01234.4 NC_000012.3 NM_01234.5 NC_000012.3 AC_45678.9 NC_000012.3 ENST012345 NC_000012.3 method self splign self splign splign blat self genebuild exons exon sets Needleman-Wunsch alignments use coordinates from source databases. What's in UTA? UTA is the Universal Transcript Archive. It stores versioned transcript and genomic exon definitions and the alignments between them. Exon coordinates in UTA are exactly as provided by the data source, not inferred or regenerated. There many cases where the transcript and genomic exon sequences differ due to sequencing errors or polymorphisms, including indels. Indel differences confound simple mapping between c. and g. coordinates and occur in several clinically- important genes. Having these alignments in UTA facilitates mapping variants even when an indel or sequence variant is present. Historical transcripts and their alignments are necessary to interpret older published data. Multiple alignment methods allow detailed and comprehensive comparisons of NCBI (splign) and UCSC (blat) exon structures, for example. UTA uses hashes of sequences, exon sets and other entities to enable rapid determination of equivalence within and across sources. Features ⨀ Parse and generate most HGVS formatted variants ⨀ Project variants between g, c, n, and p coordinates using an indel-aware mapper ⨀ Normalize variants to standard forms ⨀ Validate variants ⨀ Easy local installation ⨀ Extensively tested using manually mapped variants and comparisons with dbSNP and Mutalyzer. Interface for HGVS name analysis • Utilises the hgvs Python package • Input HGVS name into text-box • Select alignment method • Click Submit Interface for HGVS name analysis • Utilises the hgvs Python package • Input HGVS name into text-box • Select alignment method • Click Submit Tabular output of validated descriptions • Links to fasta sequences and alignments • Automated mapping between transcripts • Intronic variant descriptions accepted • Optional re-align with alternative method Tabular output of validated descriptions • Links to fasta sequences and alignments • Automated mapping between transcripts • Intronic variant descriptions accepted • Optional re-align with alternative method Code, documentation, issue tracker: https://bitbucket.org/biocommons/hgvs/ Mailing list: [email protected] Citation: A Python Package for Parsing, Validating, Mapping, and Formatting Sequence Variants Using HGVS Nomenclature. Hart RK, Rico R, Hare E, Garcia J, Westbrook J, Fusaro VA. Bioinformatics. 2014 Sep 30. CLINVITAE http://clinvitae.invitae.com/ hgvsWeb VariantAnalyser Peter. J. Freeman, Anthony. J. Brookes, Raymond Dalgleish Department of Genetics, University of Leicester, Leicester, UK https://www22.lamp.le.ac.uk/hgvs/variantanalyser hgvs functionality ⨀ Object model – facile interface to HGVS variant elements ⨀ Parser and Formatter – Converts HGVS text to Python objects, and vice versa ⨀ Variant mapper – indel-aware mapping of g. ↔ n. ↔ c. → p. ⨀ Validator – Verifies variant syntax and limited semantics ⨀ Normalizer – Rewrites variants in recommended forms