Microattribution

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Microattribution
Myles Axton HVP session ASHG San Diego 25th Oct
2007
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broad-sense human variome project

• Study phase
• 1) Collect rare clinical mutations from rare
  hereditary diseases into 700 locus-specific
  databases.
• 3) Re-sequence genes for rare variants associated
  with common diseases.
• 2) Associate common variants with common diseases
  via the HapMap and and whole genome association
  studies.

Needs Harmonize software, ontologies, formats and
criteria. Add databases. Collect, publish and
credit. Replicate associations and find causal
variants.
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Microattribution

• Journals provide citation links from paper to
  paper. Quantitative citation provides a rough
  measure of immediate usefulness.
• Database accessions should be traceable to their
  original source. Citations to database accessions
  in peer reviewed papers and database entries
  should be counted and the cumulative count made
  prominently public.
• Microcitation provides incentive for
  collaborative genome annotation and a more
  accurate picture of individual and group research
  activity.

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??
It is clear that accessions mandated by the
journal predominate, but ideally, all publicly
deposited resources should be fully cited by
authors, and properly logged and counted by the
journals.
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Peer review

• Editor commissions annotation of a locus between
  set genome coordinates. Submitters of annotations
  to NCBI who have registered to annotate the
  microattribution site qualify as authors.
• Author group led by locus-specific database
  (LSDB) expert evaluates published and database
  evidence for a phenotypic effect of each variant
  in the locus.
• Editor coordinates comments of user community
  and assigned expert peer referees. Web editor
  formats author annotations.
• Publication with digital object identifier (DOI)
  of the definitive set of annotations and links.
• Publication in new human variome journal or
  participating journals (HuGENet model) of a
  synopsis of the locus (PubMed ID).

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Elements of a microattribution browser

• Variant reports submitted to NCBI
• Retain links to LSDB and data producer with
  unique handle
• Provide an automatically updating index to genome
  via ssIDs.
• Link out to background and citing literature via
  PubMed.
• Link out to commercial assays and clinical tests.
• Detailed phenotype in dbGAP or G2P, or LSDB if
  IRB stipulates.
• Custom UCSC browser wiki track
• Displays peer reviewed variants with count of
  citing references.
• Displays current count of wiki annotations on
  each variant.

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Credit for data producers and analysts
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Links to commercial assays and clinical tests
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Microattribution browser tracks
Variant ssID links to annotations on
microattribution server
References on microattribution server are color
coded, sparklined or stacked to show numbers.
10,000 reviewed references in black, 10,001 wiki
comments in gray.
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Links from browser to curated annotations and
wiki comments
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A sample microattribution article
Ordinary human-readable text. Requires only that
variants are cited by ssID.
Edit mode
Variant ssIDs appear as clickable links
The system automatically detects links to ssIDs
and keeps a count of these.
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A sample variant page
Overview of variant, maintained manually by
author (editor or user community)
Content generated automatically
NCBI links for the variant
Citations in reviewed articles
Citations in wiki and other databases
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Software

• Wiki server
• Could use off-the shelf MediaWiki or Wiki
  Professional.
• Need to adapt page rendering so that automatic
  content is generated.
• Modify search interface so that all objects in a
  particular portion of genome can be listed.
• Modify system to help with the review process.

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Software (cont.)

• Wiki miner
• Needs to be written from scratch.
• MediaWiki uses MySQL in the backend, so this may
  be fairly easy.
• Genome browser server
• Adapt UCSC custom browser wiki to link to local
  wiki database.

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Links to commercial assays and clinical tests
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Sustainable open access publishing

• Role of publisher is to broker between vendors
  and authors.
• Authors are prepared to enrol in order to
  annotate, receive citations, uniquely identify
  selves (despite changes of family name and
  affiliation) and referee.
• Authors may endorse vendors.
• Publisher keeps count of microendorsements and
  guides vendors spend.
• Vendors may sponsor particular loci, tests or
  authors.
• Unregistered readers read for free, but cannot
  participate.

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Thanks for advice

• Gisli Masson
• Samir Brahmachari
• Mike Feolo
• Donna Maglott
• Irina Nudelman
• Tim Hubbard
• Lincoln Stein
• Paul Flicek
• Belinda Giardine
• Cover Art by Eve Stockton and Alex Beard.

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No compulsion without incentive