HL7 Clinical Genomics Weekly Call - 03 Mar 2020 11:00 AM (US Eastern)
Attending the meeting
Join the online meeting (VoIP available with this):
- Online Meeting Link:
- Meeting ID: clingenomics
Dial into the conference:
- Dial-in Number:
- (515) 604-9708 - United States
- Access Code: 289092
- International Dial-in Numbers:
Presiding Co-Chair (Kevin Power - Cerner):
- Liz Amos - NLM - firstname.lastname@example.org
- Jamie Jones - BCH - email@example.com
- Joel Schneider - NMDP/CIBMTR - firstname.lastname@example.org
- Alex Mankovich - Philips - email@example.com
- Scott Bauer - Mayo Clinic - firstname.lastname@example.org
- Bret Heale - Intermountain HealthCare - email@example.com
- Stephen Schwartz - Epic - firstname.lastname@example.org
- Clem McDonald - NLM - email@example.com
- Patrick Werner - MOLIT Institut - firstname.lastname@example.org
- Bob Freimuth - Mayo Clinic - email@example.com
- JD Nolen - Children’s Mercy Hospital - firstname.lastname@example.org
- Bob Dolin - Elimu Informatics - email@example.com
- Perry Mar - Health Catalyst - firstname.lastname@example.org
- Bob Milius - NMDP/CIBMTR - email@example.com
- Ling teng - BWH -firstname.lastname@example.org
Standing Informational Items
Agendas and Important Dates
CG Call Date
Topic 1: ‘find-variant’ operation - outstanding questions (Bob D / Patrick)
Topic 2: Update/Discussion on Implication Profiles (Jamie)
CG IG Lite: Liz & Clem
Working Group Meeting
May 16-22, 2020 • San Antonio, Texas
CG WG will be meeting Monday Q3 & Q4, and all-day Tuesday and Wednesday
- GA4GH Genomic Knowledge Standards (GKS) (leads: Bob Freimuth, Andy Yates)
- GA4GH news
- GA4GH-ISO TC215 collaborative agreement signed
- New roadmaps will be released soon
- Service discovery: draft standards open for public comment
- Variant Representation (formerly VMC) (lead by Larry Babb/Alex Wagner/Reece Hart)
- V1 RC was approved by GA4GH
- Variant Annotation
- nothing in review, continuing in modeling activities
- Phenopackets on FHIR
- Supported by NLM award to GA4GH
- Work will begin soon, currently setting up organizational framework
- Pedigree Activity (Grant Wood)
- help GA4GH community to understand HL7 Pedigree standards
- Many researchers currently using PED format - family history statement, simple, not as robust as FHIR
- Grant is co-chairing that effort
- G2MC (Grant Wood)
- Looking to develop AI tool for literature review for poly-genetic risk, generate guidance
- Create KB on G2MC website
- GEM Japan workshop (Bob Freimuth)
- Modeling and exchanging HLA results in the Japanese population
- HLA nomenclature vs discovery of new alleles
- Connecting to the HLA work done by NMDP within this WG
- ClinGen/ClinVar (Larry Babb, Bob Freimuth)
- Data Exchange/Platform WG, major driver project of GA4GH GKS
- will discuss further when Larry in on a call
- CDISC PGx (Dorina B.)
- CDISC involved in standardizing reporting of data to regulatory bodies. E.g. Pharma communication to FDA - looking to include genomics in research reporting.
- Clem: no specific insight - Transcelerate Biopharma (https://transceleratebiopharmainc.com) group fairly active in FHIR. FDA has active interest in FHIR.
- ONC Sync for Genes (Bob Freimuth)
- ONC website: https://www.healthit.gov/topic/sync-genes
- Final report for Sync for Genes Phase 2 has been finalized (but not posted yet)
- ACI manuscript is in press
- Phase 3 is kicking off - more details to be announced soon
- ISO TC/215 Genomics Subcommittee (Liz, Clem)
- March 30 - April 3, 2020 in Arlington, VA
- Liz will check to see whether the meeting is open or ISO members only
- Scott R: must be a member of a national member organization to attend
- Clem - request from them to sign-off for transmission of big data (eg BAMs), may have problems with use case.
- eMERGE FHIR adoption (Larry Babb, Mullai Murugan, Kevin Power)
- Kevin P: mostly completed their work, have not broadly shared yet. Need to finalize some details.
- Clem: is there a document summarizing their FHIR work?
- Kevin: something presented in past meetings
- Mullai: still work in progress
- May posted STU1 Candidate 1 details to Zulip (Tues Dec 17)
- Information Modeling (IM) (Bob F)
- Minutes: https://docs.google.com/document/d/15kBa3HqxQfwwe0Uwgx3UNashTIanpGRiyRVbimE_j3A/edit#
- Draft model docs: https://docs.google.com/document/d/1Wys14HNJAEB_YJ-EeDPAKX50_oxiDqAKi3WD4wlfjbk/edit
- Export of model (http://gcds.mayo.edu/HL7CG/IM_190604/model.html)
- Modeling Genotype and Copy Number Variations (CNV)
- will try to have an updated draft model posted for discussion at WGM in Sydney
- FHIR (Jamie, Gil)
- Identifying priority FHIR topics for next cycle
- Discussion split off into brainstorming doc for Implications https://docs.google.com/document/d/1SYdzxanCgkwzhhBJCBrguZ6H8HdjQFjG_l2nufAkCGU/edit#heading=h.n5eokak2o6ca
- Preparing proposals
- Genomic operations http://build.fhir.org/ig/HL7/genomics-reporting/branches/fhir_operations/operations.html
- Reducing annotation/implication profiles Simplications IG STU2
WG projects and outreach
- MOLIT will start a inter-institutional virtual tumor board project with 5 hospitals 2020/04/01 the whole persistence layer is FHIR with extensive usage of our IG. Our lab partner CEGAT (https://www.cegat.de/en/) will send the Diagnostic Reports using our profiles.
Topic 0: Approval of Minutes from Last Meeting
- Motion: Approve minutes as written
- Move / 2nd: Patrick / Clem
- Vote: (Abstain / Opposed / In Favor): 0 / 0 / 12
- Result: Motion passes
Topic 1: “Lite” IG
"Focus is on the variant. Pharmacogenomics and HLA type stuff is out. They add a lot of complexity and tend to be reported on their own and already have a pretty good start.
I treated all variants (big/little 0 the same). Did not model either genotype or haplotype. They get in the way of simplicity (but I may get fired because of that).
I focused on the 5 ways of specifying a variant. Some of our fields are convenience fields – don’t add real information, but people like them-so segregated them"
Attachments from 1/28 email
Clem: where are allelic frequency? We have a component:sample-allelic-frequency, population frequency is in the backlog.
Bret. Population frequency needs a description of the population looked at.
Clem: last four components should be grouped together.
Bob D.: how do we use arrCGH ratio?
Clem: we can remove the last four components? Of the UML (in the pdf). Wants to carve out pharmacogenomics out of the IG, or make it a distinct IG.
Bob M.: is this about modifying the CG IG? Or should this be a “simple” CG IG.
Jamie: The idea is to have a structured way of using only some parts of the IG.
Bob M.: Could do this by example and guidance
Jamie: all Components are optional
Bob D.: could see this as a review of our current variant profile.
Kevin: focus on improving the current variant (and other profiles) then we can think about a simpler version
Bret: we have redundancies as there are several ways to transport variants
Clem: wants to have a simpler way to show labs how to implement.
Bob D.: we can start with cleaning up our variant profile.
Kevin.: two approaches: get rid of a lot of stuff. Or focus on the variant level. Can do derived profiles from variant.
Patrick: i understand the need of better guidance for implementers. We should give better guidance (text, uml diagrams, graphics) how to implement a Genomics Diagnostic Report with Variants.
Kevin: Let’s start with a spreadsheet representation of Variant and Clem can mark all components he thinks aren’t necessary anymore.
Bob M.: I support Kevin's approach, but I've found the best way to show labs how to send Genomics Report bundle is with many examples with lots of comments.These examples should be showing different kinds of reports
[Mar 3, 2020 at 10:06:51 AM] Kevin Power: Minutes
[Mar 3, 2020 at 10:10:40 AM] Patrick: +1 for voting and merging to master branch
[Mar 3, 2020 at 10:16:25 AM] Liz Amos: I'm trying to add the PDF to the meeting notes but am stuck
[Mar 3, 2020 at 10:16:34 AM] Kevin Power: While I am sharing, can someone take notes? @Jamie / @Patrick / @Bob M / @Bob F ?
[Mar 3, 2020 at 10:16:40 AM] Patrick: will do
[Mar 3, 2020 at 10:16:44 AM] Bret Heale: It IS very hard to find our current IG. The one that is most visible is the old implementation guidance created during dstu3. We really should do more to expose our published IG better. +100 to Clem
[Mar 3, 2020 at 10:18:13 AM] Liz Amos: Try this one: https://drive.google.com/file/d/1PMVRyh0MRrCIzCHgvdftvRocgYQuSvLX/view?usp=sharing
[Mar 3, 2020 at 10:23:30 AM] Patrick: component:sample-allelic-frequency
[Mar 3, 2020 at 10:31:39 AM] Bret Heale: I recall that folks were not negative but asking that you use profiling to create an implementation guide as a more constrained version with less fields.
[Mar 3, 2020 at 10:32:02 AM] Jamie Jones: +1 to simplified "view" of functional ways to use variant
[Mar 3, 2020 at 10:32:02 AM] Jamie Jones: either as additional profiles or through examples
[Mar 3, 2020 at 10:33:25 AM] Jamie Jones: quick notes I drafted to help group the components based on these comments: https://docs.google.com/spreadsheets/d/1hnoaWjdNZbGkIzl4gZugzANnulQXF6ky7aWCjzbAiks/edit#gid=0
[Mar 3, 2020 at 10:38:48 AM] Jamie Jones: +1 for considering the direction, Bret
[Mar 3, 2020 at 10:39:04 AM] Bret Heale: I do not see that we have the right consortium of stakeholders in our meetings to really move the ball forward
[Mar 3, 2020 at 10:39:18 AM] Jamie Jones: I don't want us to consider removing components from Variant right now
[Mar 3, 2020 at 10:39:22 AM] Bret Heale: through implementation the field will move better
[Mar 3, 2020 at 10:39:41 AM] Jamie Jones: just don't add include them in sub-profiles and/or examples
[Mar 3, 2020 at 10:39:47 AM] Bret Heale: pardon closer to a specific normalized version of sending genetic data
[Mar 3, 2020 at 10:42:50 AM] Patrick: +100 to all of jamies statements
[Mar 3, 2020 at 10:44:11 AM] Bob Freimuth: Adoption lags for a lot of reasons, not just because the spec is complex. A big reason is that it is not yet stable.
[Mar 3, 2020 at 10:45:13 AM] Bret Heale: don't call it my principals. it was the historic perspective and guidance from the group, including specific members of this conversation.
[Mar 3, 2020 at 10:48:31 AM] Jamie Jones: "improvable" is very diplomatic
[Mar 3, 2020 at 10:49:20 AM] Bob Milius: I support Kevin's approach, but I
[Mar 3, 2020 at 10:50:20 AM] Bob Milius: I support Kevin's approach, but I've found the best way to show labs how to send Genomics Report bundle is with many examples with lots of comments.
[Mar 3, 2020 at 10:50:20 AM] Bob Milius: These examples should be showing different kinds of reports
[Mar 3, 2020 at 10:52:13 AM] Jamie Jones: https://docs.google.com/spreadsheets/d/1hnoaWjdNZbGkIzl4gZugzANnulQXF6ky7aWCjzbAiks/edit#gid=0
[Mar 3, 2020 at 10:53:15 AM] Bob Milius: This work should be based on example use cases (high level narrative on what is being reported), and then examples can be created from them.
[Mar 3, 2020 at 10:53:46 AM] Bret Heale: regards examples, you'll see that all is possible
[Mar 3, 2020 at 10:53:46 AM] Bret Heale: it depends on what the lab is willing to do bioinformatically
[Mar 3, 2020 at 10:59:03 AM] Jamie Jones: exactly, Bret
[Mar 3, 2020 at 10:59:03 AM] Jamie Jones: If we can outline common or suggested breakpoints in workflows those will drive the examples
LOINC changes for Level of Evidence / Clinical Significance
See these notes from Swapna: LOINC Significance vs Evidence and TMB code proposal.pdf
Level of evidence
See these previous call notes for earlier discussion: CG-2019-08-27
Need to consider the following two new motions:
- Motion A: Use 53037-8 for both germline and somatic variant clinical significance reporting, and add information to the Term description about the different guidelines for somatic and germline variants; Keep the Answer list the same, but update the type from Preferred to Example
o 1st/2nd -
o Discussion -
o Abstain/Nay/Yea - / /
o Result -
(Notes from Jamie:)
Want to separate clinical significance from level of evidence.
Sites want to continue to use the tier system as well.
Ask: a therapeutic somatic variant:
(note, this example uses placeholder value “AMP Guidelines” instead of a tier)
Code: somatic-predictive (TBD LOINC)
Value: E.g. Resistant, Responsive, Not-Responsive, Sensitive, Reduced-Sensitivity, Adverse Response
Component: Level of evidence -
Value: from LOINC Answer List LL5356-2 (preferred) CAN USE TIER SYSTEM HERE
- Motion B: Consider creating new codes for diagnostic, therapeutic, and prognostic significance (see Quest screenshot, LabCorp report) and/or type of evidence (see Baylor report)
o 1st/2nd -
o Discussion -
o Abstain/Nay/Yea - / /
Need to create an example to understand the meaning of this change/concepts.
Need a caretaker for this topic.
FHIR-25296 Uncallable subregions in a region studied
FHIR-24598 How to reference a region studied observation from genotype, haplotype, variant observations
FHIR-19844 PGx High Risk Allele Medication Impact is confusing
Clinical Genomics Reference Docs
- Mission & Charter
- Currently displayed here:
- Edit here:
- Approved in Sep 2019 WGM
- Review complete as of Aug 1, 2017
- Approved in Sep 2019 WGM
- Decision Making Process
- New DMP: http://www.hl7.org/documentcenter/public/procedures/Default_HL7_WG_DMP_2018.pdf
- DMP Addendum template: http://www.hl7.org/documentcenter/public/procedures/DMP_Modification_Template_2018.docx
- We will review/edit/approve by Sep 2019 WGM