The accumulation of genetic variant annotations has been increasing explosively with the recent technological advances. However, the fragmentation across many data silos is often frustrating and inefficient. We created a platform, called MyVariant.info (http://myvariant.info), to aggregate variant-specific annotations from community resources and provide high-performance programmatic access. Annotations from each resource are first converted into JSON-based objects with their id fields as the canonical names following HGVS nomenclature (genomic DNA based). This scheme allows merging of all annotations relevant to a unique variant into a single annotation object. A high-performance and scalable query engine was built to index the merged annotation objects and provides programmatic access to the developers. MyVariant.info decouples two fundamental steps in management of variant annotations: the creation and maintenance of centralized web services (which requires deep software-engineering expertise), and the task of structuring biological annotations (which requires broad community effort). Annotation providers from the community can provide data parsers to convert their raw data into JSON-compatible objects. The only requirement is that a valid HGVS name is used as the id field for each object. These data can then be queryable through the query engine we built. The data provider doesn’t have to worry about building their own query infrastructure. And the research community doesn’t have to learn another query interface in order to access new annotations.

1. Jiwen (Kevin) Xin, Cyrus Afrasiabi, Sean D. Mooney, Andrew I. Su, Chunlei Wu
kevinxin@scripps.edu
The Scripps Research Institute
La Jolla, CA, USA
NGS 2016
04/05/2016
MyVariant.info
Community-aggregated Variant Annotations As a Service

2. So many variant annotation resources
dbNSFP

3. Schematic view of MyVariant.info architecture
Each data source is updated individually. Colors
indicate their different updating schedules.

4. HGVS name examples
Table . Examples of HGVS (Human Genome Variation Society) nomenclature.

5. MyVariant.info for the end users:
http://MyVariant.info
(currently v1 API, two endpoints)
http://MyVariant.info/v1/query?q=<query>
any query term(s)
matching variant hits
http://MyVariant.info/v1/variant/<variantid>
hgvs id(s)
matching variant object(s)
Both supports batch-mode via POST
Simple API. No sign-up. No API key.
Try our live API , and documentations

6. http://myvariant.info/v1/variant/chr1:g.31349647C>T
Retrieving a single variant
Integrated annotations across
resources in well-formatted data
structure
Always up-to-date
http://myvariant.info/v1/variant/chr1:g.31349647C>T

7. http://myvariant.info/v1/variant/chr1:g.31349647C>T?fields=dbnsfp
http://myvariant.info/v1/variant/chr1:g.31349647C>T?fields=dbnsfp.clinvar
http://myvariant.info/v1/variant/chr1:g.31349647C>T?fields=dbnsfp.clinvar,dbsnp
.gmaf,clinvar.hgvs.coding
Filtering returned fields

8. Making flexible queries
• All variants with dbNSFP annotation:
http://myvariant.info/v1/query?q=_exists_:dbnsfp
• All non-synonymous variants on gene "BTK":
http://myvariant.info/v1/query?q=dbnsfp.genename:BTK
• All variants within a genomic range:
http://myvariant.info/v1/query?q=chr1:69000-70000
• Query Wellderly variants together with other annotation sources:
http://myvariant.info/v1/query?q=_exists_:wellderly AND cadd.polyphen.cat:possibly_damaging
&fields=wellderly,cadd.polyphen

9. Many more ways of querying, across resources
 Full-text queries
 Wildcard queries
 Range queries
 Boolean queries
 Regex queries
 Field existing/missing
 Faceting
 Paging
 Sorting
 Batch queries
 Support JSONP, CORS
 …

10. MyVariant.info stats
• total (334,293,820)
• dbNSFP (82,030,830; v3.0)
• dbSNP (145,132,257; v144)
• ClinVar (131,383; 201602)
• EVS (1,977,300; v2)
• CADD (226,932,858; v1.3)
• MutDB (420,221)
• gwassnps (15,243; from UCSC)
• COSMIC (1,024,498; v68 from UCSC)
• DOCM (1,119)
• SNPedia (5,907)
• EMVClass (12,066)
• Wellderly (21,240,519)
• EXAC (10,195,872; v0.3)
• GRASP (2,212,148; v2.0.0.0)
As of April, 2016

11. MyVariant.info official Python/R Clients
myvariant Python client hosted in PyPI
(initial release in Aug 2015)
myvariant R client hosted in Bioconductor
(initial release in Oct 2015)

12. Use case 1
An easy resource to retrieve
well-structured variant
annotations

13. Use case 2
Direct queries integrated in your
analysis pipeline

14. User Case 2: An example workflow for variant prioritization
input variants
output variants
filter1 <- lapply(vars, function(i) subset(i,
cadd.consequence %in% c("NON_SYNONYMOUS",
"STOP_GAINED", "STOP_LOST", "CANONICAL_SPLICE",
"SPLICE_SITE")))
filter2 <- lapply(filter1, function(i)
subset(i, exac.af < 0.01))
filter3 <- lapply(filter2, function(i)
subset(i, sapply(dbnsfp.1000gp1.af, function(j)
j < 0.01 )))

15. Use case 3
For curator/data provider:
A platform for
integrating with other resources
(saving repetitive efforts)
distribute your valuable data
(under your own source field)

16. Use case 4
For variant curation itself:
Identify discrepancies
Serve as the base of community-engaged curation
process

17. Linked data
URI (Uniform Resource
Identifier):
Provide unique identifier for
anything or any concept on the
website
Connective:
connecting data, concepts,
applications and ultimately
people.
URL (Uniform Resource Link):
Provide unique identifier for
webpages
Text files, images, music, videos
Interactive:
Twitter, Facebook, blogs

18. Why Linked Data?
Providing Unique Identifier for a concept
Genenam
e
e.g. CDK2
genename,
(database1)
gene_name,
(database2)
{’gene’: {‘name’:…}},
(database3)
URI:
http://identifiers.org/hgnc.symb
ol

19. Data Discrepancy ---- Example
http://myvariant.info/v1/variant/chr12:g.111351981C>T?fields=clinvar.rsid,dbsnp.rsid,evs.rsid

20. Data Discrepancy ---- Example 2
EVS web browser EVS txt data file

21. Acknowledgement
Funding and Support
U54GM114833
U01HG008473
Washington U:
Ben Ainscough
Obi Griffith
TSRI:
Chunlei Wu
Andrew Su
Jiwen Xin
Cyrus Afrasiabi
Ginger Tsueng
Adam Mark
Greg Stupp
Tim Putman
STSI:
Eric Topol
Ali Torkamani
Galina Erikson
U. Washington:
Sean Mooney
Moritz Juchler
Nikhil Gopal
OICR:
Robin Haw
UC Berkeley:
Chris Mungall
UCSD:
Trish Whetzel
MyVariant.info

22. MyVariant.info Clients
API:
https://myvariant.info
Python Client:
https://pypi.python.org/pypi/myvariant/
R Client:
http://bioconductor.org/packages/release/bioc/html/myvariant.html.
Jupyter Notebook Tutorial for Python Client (Focus on Clinvar):
https://cdn.rawgit.com/SuLab/myvariant.info/master/docs/ipynb/myvari
ant_clinvar_demo.html