Last modified on 27 November 2013, at 16:38
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:email@example.com Participant Access Code: 4257 ("HCLS") IRC Channel: irc.w3.org port 6665 channel #HCLS
- 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.
- From Matthias
- 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.
(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 [~firstname.lastname@example.org] 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 [email@example.com] 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_ [~firstname.lastname@example.org] 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_ [~email@example.com] has joined #HCLS [17:18] <matthias_samwald> michel: i am also interested in drug-drug-gene interactions [17:19] == jose [~firstname.lastname@example.org] 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