HCLSIG/Pharmacogenomics/Meetings/2013-11-27 Conference Call

Meeting:      Clinical Pharmacogenomics
Date:         November 27, 2013
Time:         10:15 Eastern Time (16:15 Central European Time)
Conveners:    Michel Dumontier, Matthias Samwald
Dial-In #:    +1.617.761.6200 (Cambridge, MA)
VoIP address: sip:zakim@voip.w3.org
Participant   Access Code: 4257 ("HCLS")
IRC Channel:  irc.w3.org port 6665 channel #HCLS

Suggested Agenda

Report on progress and insights over the few last months
- From Matthias
  - New team-member (post-doc) started working full-time on the project (and a few side-projects): Jose Antonio Minarro Gimenez
  - Complete overhaul of the pharmacogenomics decision support service driving http://safety-code.org/ (but not public yet). Now based on OWL 2 reasoning for decision support. Beside uploading files (in 23andMe and VCF formats) and decoding an MSC QR code, a third option is about to be added: manual entry of genetic variants through mobile-friendly user interface. Prototypical implementation for azathioprine dosing based on TPMT alleles.
  - Spreadsheet containing curated pharmacogenomics rules significantly extended thanks to help from new team member Kathrin Blagec (final-year medical student). This file is used by scripts that generate the Genomic CDS ontology. Needs to be validated, checked for consistency and further curated. Link to Excel sheet.
  - Started collaboration with local clinician (transplantation medicine)
  - Invited editorial published in the journal Pharmacogenomics together with Bob Freimuth: http://www.futuremedicine.com/doi/full/10.2217/pgs.13.121
  - Manuscript about Genomic CDS ontology for pharmacogenomics knowledge representation and decision support submitted to journal Bioinformatics, under review.
  - Paper about technical aspects of the new version of the Medicine Safety Code decision support fram
  - Medicine Safety Code paper published earlier this year was recently highlighted in AMIA's 2013 in review. Also won a distinguished paper award at Medinfo2013 a few months ago for this work.
Discussion about required steps for transitioning from academic research / proof-of-concept towards real clinical / industrial applications. Developing strategies for networking with stakeholders, generating a public profile, evaluation in realistic clinical settings.
Discussion of schedule - http://www.w3.org/wiki/HCLSIG/Pharmacogenomics#Schedule - Are we making progress as planned? Add new milestones for 2014.

Meeting Minutes

(for technical reasons, we can only provide the raw IRC log - sorry)

[16:21] <Zakim> On the phone I see matthias_samwald, ericP, bobf, michel
[16:21] <matthias_samwald> http://www.w3.org/wiki/HCLSIG/Pharmacogenomics/Meetings/2013-11-27_Conference_Call
[16:22] == boycer [~boycer@public.cloak] has joined #hcls
[16:23] <boycer> should be able to join the call in <10 minutes
[16:24] <michel> welcome Jose!
[16:25] <ericP> topic: http://safety-code.org/ update
[16:25] <ericP> matthias_samwald: [introduces a post-doc: Jose Antonio Minarro Gimenez]
[16:26] <ericP> ... mostly completed overhaul
[16:26] <ericP> ... switch to using OWL-2
[16:26] <jose> using TrOWL reasoner
[16:27] <ericP> ... barcode decode and deref kicks off reasoner and yields @@1
[16:27] <ericP> jose, can you write something like "s/@@1/what the website displays"?
[16:27] <ericP> matthias_samwald: addressing network delays and performance issues
[16:28] <ericP> ... i.e. using caching
[16:29] <jose> http://owl.msi.meduniwien.ac.at:8080/Genomic-CDS/v0.2/QXGqrLF2h8xuqzIyCGJE2hzPzVzrND_q0vtKk2krxy0gQgDMlxWI0dzPwTq51w2UACs2nwZlF3QRxkv3uuuQtj4S55rDHGVU26maAZ203z-RCqhavsFv0a5uY1q770Su7_dg80000
[16:29] <matthias_samwald> CPIC
[16:29] <matthias_samwald> DPWG
[16:29] <jose> example of MSC server results
[16:29] <ericP> ... we're building all of this on the CDS ont, DBSNP, PharmGKB, decision suport CPIC and DPWG
[16:29] * ericP tx, jose
[16:30] <ericP> BobF: happy to review the alleles
[16:31] <ericP> ... i intented to model the CPIC guidelines and the star alleles, but it seems you've already done it
[16:31] <ericP> matthias_samwald: some issues: @@2, @@3, descriminating tag and non-tag SNPs
[16:32] <ericP> BobF: we need to document which alleles were used for which star names
[16:32] <ericP> ... these vary amoung sites, so it's possible that different sites will look at different SNPs
[16:33] <ericP> matthias_samwald: thanks to the OWL, we can document that and look for inconsistancies
[16:33] <ericP> BobF: I'm investigating how star alleles will work with nextgen data
[16:34] <ericP> ... i'd like to demonstrate the ambiguity introduced by the nomenclature system
[16:34] <ericP> ... the tech that you've built will help demonstrate this
[16:35] <ericP> matthias_samwald: the most difficult challenge will be teasing out what different systems are using
[16:35] <ericP> BobF: we've been discussing this in PGRNTPP
[16:36] <ericP> ... we have different platforms using different methodologies to map the same sequences [did i get that right?]
[16:37] <ericP> ... in some systems, the genotyping platform picks the alleles
[16:37] <matthias_samwald> different platforms act like black boxes when inferring alleles from raw genetic data
[16:37] <ericP> s/picks the alleles/picks the star alleles/
[16:37] <michel> it's crazy that the genotyping platform doesn't reveal the composition of the star allele...
[16:40] <ericP> scribenick: ericP
[16:40] == RRSAgent [rrsagent@public.cloak] has joined #hcls
[16:40] <RRSAgent> logging to http://www.w3.org/2013/11/27-hcls-irc
[16:40] * ericP weak!
[16:42] <Zakim> + +1.206.371.aabb
[16:42] * ericP michel, can you take over scribing? i've got a tiny little problem
[16:42] <ericP> Zakim, aabb is rboyce
[16:42] <Zakim> +rboyce; got it
[16:42] <ericP> Zakim, rboyce is really boycer
[16:42] <Zakim> +boycer; got it
[16:43] <matthias_samwald> http://genomic-cds.googlecode.com/svn/knowledge-base/trunk/data/decision-support-rules/Pharmacogenomics%20decision%20support%20spreadsheet.xlsx
[16:46] <jose> just use save as option!
[16:46] <jose> on the link
[16:46] <matthias_samwald> http://www.futuremedicine.com/doi/full/10.2217/pgs.13.121
[16:50] <matthias_samwald> bobf: feeding PGRNseq data into MSC could be an important next step
[16:51] <matthias_samwald> bobf: either through dedicated process or via generic VCF files
[16:51] <matthias_samwald> ... however there have been delays in getting the platform ready for clinical (rather than research) purposes
[16:51] <matthias_samwald> ... that process should be finished by the end of the year
[16:52] <matthias_samwald> ... once this is finished, we will have data to demonstrate how MSC can work with real clinical data from PGRNseq
[16:52] <matthias_samwald> richard: what is the CLIA approval status of the PGRNseq?
[16:53] <matthias_samwald> bobf: it is a custom platform from the PGRN community.
[16:53] <matthias_samwald> ... intended for both research and clinical application
[16:53] <matthias_samwald> ... was first developed by U of Washington
[16:53] <matthias_samwald> ... then distributed to partners in PGRN / eMERGE
[16:53] <matthias_samwald> ... some are using / hope to use it in clinical settings
[16:54] <matthias_samwald> ... for clinical, PGRNseq will be used in a CLIA lab
[16:54] <matthias_samwald> ... but these problems are having problems getting good coverage of some of the more 'tricky' genes, so the platform cannot be used to genotype these genes
[16:55] <matthias_samwald> ... clinical thresholds for sequencing coverage are not met
[16:55] == egonw_ [~egonw@public.cloak] has quit [Ping timeout: 180 seconds]
[16:55] <matthias_samwald> ... labs are experimenting on how to change sequencing conditions to get sufficient coverage.
[16:57] <matthias_samwald> bobf: another topic is the Cerner CBO
[16:57] <matthias_samwald> bobf: have not made much progress with this
[17:00] * ericP Zakim, mute me
[17:00] * Zakim ericP should now be muted
[17:03] <matthias_samwald> bobf: how can we extend the Genomic CDS / reasoning system for complex interactions / gene-gene interactions?
[17:03] <matthias_samwald> ... warfarin would be a good starting point
[17:04] <matthias_samwald> ... and start looking at metabolic pathways
[17:04] <matthias_samwald> ... instead of looking at genes in isolation
[17:06] <matthias_samwald> richard: i am interested in this as well. i have a protocoll for a study (for psychotropic medications)
[17:07] <matthias_samwald> ... interesting interactions: if an allele is already non-functional, inhibiting the corresponding enzyme does not change much. this can be very different for rapid metabolizers.
[17:07] <matthias_samwald> ... we have a set of relevant drugs and interactions, still missing patients
[17:08] <matthias_samwald> ... could use approach recently used by matthias, using openly available 23andMe profiles to 'simulate' patients.
[17:08] <matthias_samwald> ... can you give an example of gene-gene-drug interaction?
[17:09] <matthias_samwald> bobf: an example would be warfarin, vkorc1 and cyp2c9
[17:09] <matthias_samwald> ... but there could be more sophisticated interactions
[17:09] <matthias_samwald> ... cancer chemotherapy would be a good use-case
[17:10] <matthias_samwald> ... not necessary to become systems biologists... just try to use pathway databases.
[17:11] <matthias_samwald> .. richard: need to prioritize scenarios to get towards real clinical impact
[17:12] <matthias_samwald> michel: working on building group here in stanford
[17:13] <matthias_samwald> ... bringing resources online
[17:13] <matthias_samwald> ... generating bio2rdf datasets
[17:13] * ericP Zakim, please unmute me
[17:13] * Zakim ericP should no longer be muted
[17:14] <matthias_samwald> ... re-calculating statistics
[17:14] <matthias_samwald> ... improved dbSNP importer for Bio2RDF. still don't import entire dbSNP, need to select relevant SNPs
[17:14] <matthias_samwald> ericP: do you need assistance with dbSNP?
[17:15] <matthias_samwald> matthias: i assume all SNPs mentioned in PharmGKB are important from dbSNP?
[17:15] <matthias_samwald> michel: yes.
[17:16] <matthias_samwald> bobf: NCBI's Clinvar might also become relevant
[17:16] <matthias_samwald> ... it is a hyrid of dbSNP and OMIM
[17:17] <matthias_samwald> ... trying to come up with functional consequences of mutations reported in clinical sequencing reports.
[17:17] == egonw_ [~egonw@public.cloak] has joined #HCLS
[17:18] <matthias_samwald> michel: i am also interested in drug-drug-gene interactions
[17:19] == jose [~jose@public.cloak] has quit ["Page closed"]
[17:29] <matthias_samwald> (more detailed discussion about drug-drug-gene interactions and how to deal with them is not captured)
[17:30] <boycer> http://www.genome.gov/27546194
[17:31] <boycer> That link deacribes the Clinical Sequencing Exploratory Research (CSER) project