Next Generation Cancer Data Discovery, Access, and

Integration Using Prizms and Nanopublications

Jim McCusker@jpmccu, Timothy Lebo@timrdf, Michael Krauthammer,

and Deborah McGuinness@dlmcguinness

What we’re trying to fix From: Data Sharing and Management SNAFU in 3 Acts

What we’re trying to fix

Ah yes, SAM1 is the level of CXCR4 expression.

What is the content of the field called

“SAM1”?

From: Data Sharing and Management SNAFU in 3 Acts

What we’re trying to fix

That is logical if you think about it.

And what is the content of the field

called “SAM2”?

From: Data Sharing and Management SNAFU in 3 Acts

What we’re trying to fix

… What is the content of the field called

“SAM2”?

I don’t remember.

From: Data Sharing and Management SNAFU in 3 Acts

Life Science data seems to start its life very

scruffy.

5 Levels of Data Sharing, from scruffy to neat

Level 1: Basic data sharing Who, what, when, where, why

Level 2: Automated Conversion Computable RDF representations

Level 3: Semantic enhancement Human-enhanced RDF representations

Level 4: Semantic eScience Use of vocabularies with formal semantics

Level 5: Community-Based Standards Consensus use of preferred ontologies

The Prizms Architecture

Prizms User Interactions

Provenance of Prizms

Prizms

healthdata.tw.rpi.edu

lod.melagrid.org

More Prizms Nodes: https://github.com/timrdf/prizms/wiki/Prizms-Nodes

prov:wasDerivedFrom

prov:wasDerivedFrom

Linking Open Govt. Data prov:wasDerivedFrom

5 Levels in Prizms

Level 1: Basic data sharing CKAN dataset metadata + datapubs

Level 2: Automated Conversion Prizms raw conversions

Level 3: Semantic Conversion Prizms enhanced conversions

Level 4: Semantic eScience Level 3 + NCBO ontology recommender + similar tools

Level 5: Community-Based Standards Level 4 + Vocabulary reuse analysis

Level 1: Basic Data Sharing

CKAN1 and Datapubs

1Comprehensive Knowledge Archive Network

What is CKAN?

•  A data portal for all kinds of data

•  Link or upload •  Linked Data-

friendly •  Link to:

o  Files o  APIs o  SPARQL

endpoints o  Metadata o  Publications o  Visualizations…

•  A data portal for all kinds of data •  Link or upload

•  Linked Data-friendly •  Link to: o  Files

o  APIs o  SPARQL endpoints

o  Metadata o  Publications

o  Visualizations…

data.melagrid.org A portal for melanoma data

What is a Datapub?

Viewing Relations, Attributes, and Entities in RDF (VRAER)dl.dropboxusercontent.com/u/9752413/dils2013/exome-‐‑variants-‐‑in-‐‑melanoma.ttl Redraw

hasAttribution

hasSupporting

hasAssertion

hasProvenance

exome-variants-in-melanomaa Nanopublication

provenancea Provenance

attributiona Attribution

supportinga Supporting

assertiona Assertion

Groth et al., 2010

Anatomy of a Datapub: Assertion

Viewing Relations, Attributes, and Entities in RDF (VRAER)http://dl.dropboxusercontent.com/u/9752413/dils2013/exome-‐‑variants-‐‑in-‐‑melanoma-‐‑assertion.ttl Redraw

IMT

homepage

distribution

exome_aa_variants_final.xlsa DistributionaccessURL: exome_aa_variants_final.xls

xls

value: xls

Variant data from "Exome sequencing identifiesrecurrent somatic RAC1 mutations in melanoma"

a Datasetdescription: Variant data from M. Krauthammer, Y. Kong, B. Ha,

P. Evans, A. Bacchiocchi, J.P. McCusker, E.Cheng, M.J. Davis, G. Goh, M. Choi, S. Ariyan, D.Narayan, K. Dutton-Regester, A. Capatana, E.C.Holman, M. Bosenberg, M. Sznol, H.M. Kluger, D.E.Brash, D.F. Stern, M.A. Materin, R.S. Lo, S. Mane,S. Ma, K.K. Kidd, N.K. Hayward, R.P. Lifton, J.Schlessinger, T.J. Boggon, and R. Halaban, Exomesequencing identifies recurrent somatic RAC1mutations in melanoma. Nature Genetics, 2012. inpress. **Tab 1: Description** This worksheetcontains a description of the variant calling method.**Tab 2: SNVs** This worksheet containsautomatically called somatic non-silent SNVs inmatched melanoma samples. Annotations fromMU2A. **Tab 3: InDels** This worksheet containsautomatically called somatic InDels in matchedmelanoma samples. Annotations from VEP. **Tab 4:Splice Site Variants** This worksheet containsautomatically called somatic splice site variants inmatched melanoma samples. Annotations fromVEP. **Tab 5: Additional mutations** This worksheetcontains additional somatic mutations. Thesemutations are either inferred in unmatched samples(see Methods overview above), or have beenSanger-validated via PCR amplified products, aftermanual inspections of sequencing reads.Annotations from MU2A/VEP. Nomenclature --------**SNV:** Single Nucleotide Variant **DNV:**Dinucleotide Variant **DNV*: ** Two SNVs affectingthe same codon, at positions 1 and 3 of the codon**TNV:** Trinucleotide Variant **Parentheses ingenotype calls:** Nucleotides that appear inparentheses are true variant calls in tumor whichhave not been called somatic by the automaticpipeline. These variants are shown if anotherposition in the same codon has a somatic call. Thecorresponding SNP position, if known, is alsoshown. **InDel:** Insertions and Deletions**HGVS:** Human Genome Variation Societyvariant format **COSMIC:** Catalogue of SomaticMutations -http://www.sanger.ac.uk/perl/genetics/CGP/cosmic/**SNP:** This column provides SNP-IDs if availablefor any the mutated positions in tumors **PhyoP:**Computation of p-values for conservation oracceleration(http://compgen.bscb.cornell.edu/phast/faq.php).Data from UCSC genome browser. References ------ **MU2A:** Garla V, Kong Y, Szpakowski S,Krauthammer M. MU2A--reconciling the genomeand transcriptome to determine the effects of basesubstitutions. Bioinformatics. 2011 Feb 1;27(3):416-8. Epub 2010 Dec 12. PubMed PMID: 21149339;PubMed Central PMCID: PMC3031033. **VEP:**McLaren W, Pritchard B, Rios D, Chen Y, Flicek P,Cunningham F. Deriving the consequences ofgenomic variants with the Ensembl API and SNPEffect Predictor. Bioinformatics. 2010 Aug

15;26(16):2069-70. Epub 2010 Jun 18. PubMedPMID: 20562413; PubMed Central PMCID:PMC2916720.

keyword: exome-sequencing, homo-sapiensidentifier: exome-variants-in-melanoma

Anatomy of a Datapub: Attribution, Evidence

Viewing Relations, Attributes, and Entities in RDF (VRAER)http://dl.dropboxusercontent.com/u/9752413/dils2013/exome-‐‑variants-‐‑in-‐‑melanoma-‐‑attribution.ttl Redraw

contributor

creatorexome-variants-in-melanoma

rights: cc-by

James McCusker

mbox: mailto:james.mccusker@yale.edu

Michael Krauthammer

mbox: mailto:michael.krauthammer@yale.edu

Attribution

Evidence

Citing a Dataset using Datapubs

Citing a Dataset using Datapubs

Levels 2-3: Automated Conversion, Semantic

Conversion Prizms raw conversions, enhanced conversions

Prizms RDF Converter

smart, naïve bootstrap

"Hawaii","Alii Garden Market Place", "75-6129 Alii Drive", "Kailua-Kona", "96740", "-155.9819183", "19.61436844"

ds4383:thing_1367 raw:column_1 "Hawaii"; raw:column_2 "Alii Garden Market Place"; raw:column_3 "75-6129 Alii Drive"; raw:column_4 "Kailua-Kona"; raw:column_5 "96740"; raw:column_6 "-155.9819183"; raw:column_7 "19.61436844" .

ds4383:thing_1367 con:preferredURI ds4383:farmersMarket_1367 .

ds4383:farmersMarket_1367 a ds4383_vocab:FarmersMarket; con:address :address_1367; dcterms:title "Alii Garden Market Place"; wgs:lat -155.9; wgs:long 19.6 .

:address_1367 a con:Address; con:stateOrProvince typed_state:Hawaii; con:street "75-6129 Alii Drive"; con:city "Kailua-Kona"; con:zip "96740" .

typed_state:Hawaii a ds4383_vocab:State; dcterms:identifier "Hawaii"; rdfs:label "Hawaii"; owl:sameAs <http://sws.geonames.org/5855797/>, govtrackusgov:HI, dbpedia:Hawaii .

enhancementTime Domain

ExpertiseSemWebExpertise

Time Domain Expertise

SemWebExpertise

Lebo et al., 2012

Prizms Benefits

Prizms has worked with: • BFO/IAO/OBI • SIO • RDF Data Cube

Vocabulary • PROV • VOID • FOAF • etc.

For free, you get: • Provenance at

dataset and triple levels

• Automatic source/dataset/version URI generation

• Automated conversion as data changes

Future Work: Supporting Levels 4-5

Level 1: Basic data sharing CKAN dataset metadata + datapubs

Level 2: Automated Conversion Prizms raw conversions

Level 3: Semantic Conversion Prizms enhanced conversions

Level 4: Semantic eScience Level 3 + NCBO ontology recommender + similar tools

Level 5: Community-Based Standards Level 4 + Vocabulary reuse analysis✔✔

✔

✔

✔

Publishing Custom Linked Data Using LODSPeaKr

•  Custom templates for RDF and HTML

•  Templates driven by rdf:type

•  Web-based template editor

•  Embed easy-to-generate visualizations

Conclusions

•  Prizms is an infrastructure for sharing data on many levels of sophistication

•  Good support for Level 1-3 Data Sharing •  Initial support for Level 4-5 Data Sharing •  Didn't just make life science data better, it made future

Linked Data better! •  More to be done, but lots of progress

Thanks!

• Rensselaer Polytechnic (Tetherless World): o  Alvaro Graves o  John Erickson o  The LOGD Team

• The Open Knowledge Foundation Network (OKFN)

• Yale University: o  Ruth Halaban o  Tobias Kuhn

• Grant support from: o  Yale SPORE in Skin Cancer o  Semantic Sea Ice Interoperability Initiative