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HL7 Clinical Genomics Weekly Call - 5 May 2020 11:00 AM (US Eastern)

Minutes

http://tinyurl.com/HL7CGGroupCall 

https://docs.google.com/document/d/12-uBrMmav71a3_c9h_FXQteJo_I5Kt72NEBYXZuwhFg/edit

Archive of minutes: https://confluence.hl7.org/pages/viewpage.action?pageId=25559917&src=contextnavpagetreemode

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Meeting ID: 298 006 8716

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Agenda

Attendees Sign-in

Presiding Co-Chair (Bob Milius - NMDP/CIBMTR - bmilius@nmdp.org  ): 

  1. Arthur Hermann - Kaiser Permanente - arthur.hermann@kp.org
  2. JD Nolen - Children’s Mercy Hospital - jlnolen@cmh.edu
  3. Patrick Werner - MOLIT Institut - patrick.werner@molit.eu 
  4. Kevin Power - Cerner - kpower@cerner.com  
  5. Bob Dolin - Elimu Informatics - bdolin@elimu.io 
  6. Liz Amos - liz.amos@nih.gov 
  7.  Jamie Jones - BCH - james.jones.bch@gmail.com
  8. Joel Schneider - NMDP/CIBMTR - jschneid@nmdp.org
  9.  Michelle Barry-Availit, LLC , michelle.barry@availity.com 
  10.  Dora Finkeisen - MOLIT Institut - dora.finkeisen@web.de
  11. Bob Freimuth - Mayo Clinic - freimuth.robert@mayo.edu
  12. Bret Heale - Intermountain - bheale@gmail.com 
  13. May Terry - MITRE - mayT@mitre.org 
  14. Rachel Kutner - Epic - rkutner@epic.com  
  15. Clem McDonald - NLM - clemmcdonald@mail.nih.gov 

Standing Informational Items

Agendas and Important Dates 

CG Call Date

Co-Chair

Agenda https://confluence.hl7.org/display/CGW/Future+Topics+for+Weekly+Meetings

Important Dates

2/18/20

Patrick



2/25/20

Kevin

Topic 1: ‘find-variant’ operation - outstanding questions (Bob D / Patrick)

Topic 2: Update/Discussion on Implication Profiles (Jamie)


3/3/20

Kevin

CG IG Lite: Liz & Clem
Attachments from 1/28 email


3/10/20

Bob M

1: CMS/ONC rules 

2: Vote on operations for IG

3: STU2 of IG


3/17/20

Kevin

1: Reminder - CMS/ONC rules 

2: STU2 of IG (cont...)


3/24/20

Bob M

Tumor/normal examples to review 


3/31/20

Patrick



4/7/20

Bob M



4/14/20

Patrick



4/21/20

Bob M

1: old projects

2: connecathon

3: emerge extensions


4/28/20

Patrick



5/5/20

Bob M

  • Co-chair elections
  • Connectathon - Scenarios
  • "Associated" phenotype/cancer component discussion from FHIR subgroup
  • appropriate way to structure our 'additional text' extension?
  • how to link to region studied?
  • Uncallable subregions in a region studied

5/12/20

Patrick



5/19/20

Bob F

Sync for Genes


Working Group Meeting

Cancelled! May 16-22, 2020   •   San Antonio, Texas

Register Today!

CG WG will be meeting Monday Q3 & Q4, and all-day Tuesday and Wednesday

Register Connectathon: https://www.hl7.org/events/fhir/connectathon/2020/05/

Joint call with OO

  • JD Nolen: Would May 14th, Thursday, 10-1130 ET work for CG? 
  • during the normal IM call
  • Topics
    • DR (lab report) - likely main topic
    • Specimen
    • plans for MolecularSequence?
    • Device
  • other groups may be invited (BRR, II) but likely just CG and OO

External efforts

Subgroup reports

  • 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)
    • Currently looking at tooling to develop a logical model from our conceptual model
      • Kevin and Scott are leading that effort, nearly complete
    • Bob F is working on a first draft of a logical model that can be brought through the tooling, will look for input and feedback soon (join an IM call to learn more)
    • Will turn to Kevin P for Logical Model to be included in IG (IM is very conceptual, need to to create a Logical Model that will align more closely to FHIR)
    • Arthur: will DAM be updated?
    • Bob F: separate artifacts being developed, need to harmonize. Use case in DAM informed the model.
    • Bob M: our PSS says we will include use cases and IM together.
    • Bob F: these are very large, combing them will be too big to be useful?
    • Kevin: can just mention the IM and FHIR Logical Model in the DAM
    • Arthur: one way or another, they need to be harmonized
    • Bob F: bring this back as topic after Logical Model is done.
  • FHIR (Jamie)
    • Minutes:

https://docs.google.com/document/d/1FGCQRtxJKyHhnC1uB_t4sJZ9yXbLMGOqPXHPr5tSLLQ/

New simplified implications live on CI build 

http://build.fhir.org/ig/HL7/genomics-reporting

WG projects and outreach

  • none

Topic 0: Approval of Minutes from Last Meeting

April 28 

Topic 1: Co-chair election

    • Election this summer
    • Terms that end on Dec 31, 2020 - Bob M, Gil, Jamie
    • If you are interested, nominate yourself!
    • NOTE: Any individual who wants to run for election, including current and interim co-chairs, must be nominated or submit a nomination.  Additionally, nominees are required to be either a current individual member or representative of a current organizational or Affiliate member (although not necessarily a voting member).  Co-chairs are required to retain an active membership throughout their term.  Failure to do so will result in the co-chair being denied access to the HL7 ballot desktop and not being listed as a co-chair on the website.  Individuals who fail to comply will also be denied co-chair benefits, including the ability to upload minutes or update files on the NIB site.


  • Clinical Genomics - electing three co-chairs to fill the positions currently held by Gil Alterovitz, James Jones (Interim), and Bob Milius (all of whom may be re-elected)


Topic 2: Virtual Connectathon - Scenarios

  • Cancer Analysis (without risk screening) (Patrick, Alex)
    • Including tumor-normal testing
    • Tumor only testing
  • ACMG screening (Bob D, Bret)
    • Expose $find-subject-variants API (genomic data server with 300 1000-Genomes patients)
    • Use variants in an ACMG screening pipeline
    • Reassess ACMG screening after genomic data changes
    • American College of Medical Geneticists
  • who registered?
    • Bob M (likely be in FSH track)
    • Kevin
    • Patrick
    • Jamie (will register soon)
    • May (registered, but will be in different track)
    • Clem's group (registered, but will be in different track)
    • Michelle Barry
    • Bret H

Topic 3: "Associated" phenotype/cancer component discussion from FHIR subgroup

FHIR-26945: clarifying 'context' vs 'risk-of' for associated phenotype and/or associated cancer component (Bret H)

"In the Genomics FHIR IG the fields of associated cancer and associated phenotype components do not have clear guidance on how to distinguish 'risk of' versus 'context.' Perhaps, the use of the component in therapeutic implication profile indicates 'context,' whereas the use of the component in diagnostic implication profile indicates 'risk of?'

If necessary, maybe a flag would be appropriate? or some other modifier element could be added?


Diagnostic Implication has components

  • (probably) associated-phenotype *currently unbound
    • Associated with the variant
  • Associated-cancer *currently unbound
    • Associated with the variant in the referenced knowledge artifact

Therapeutic Implication currently has the same components - but the usage is different

  •  (probably) associated-phenotype *currently unbound
    • Associated with the variant in context of taking the given medication
  •  Associated-cancer *currently unbound
    • Contextual for the referenced knowledge artifact

“Phenotype” vs “cancer” convey different layers of information - cancer may be a collection of phenotypes w/ other info

  • Rachel Kutner: My understanding based on reports I've seen is that there can be a difference between diagnostic associated disease and associated phenotypes based on Germline testing



That, for example, a variant may be resulted with "Positive for Lynch Syndrome" which then has associated increased risk for different cancers



and there will be variant-specific information detailing beyond just the syndrome information with study-specific information that is unique to the variant detected

  • Bret: doesn't like to add flag or additional fields, but in this case suggest had flag for "risk of" or "context"
  • Bob F: Flags work when there are a small and finite number of terms. Are there examples of both of those terms being used together? Could other terms be added in the future? Perhaps we should consider a value set.
  • Rachel: I like the idea of flagging information to make the context clear
  • Arthur: do we have a lab result example that we can ground this?
  • Clem: need to be careful about over-engineering this and making this too complicated. Make it in narrative.
  • Bob F: Thanks to everyone for the careful analysis of meaning here. Semantics matter. :-)
  • Bob M: do an experiment using a lab result example.
  • Consensus: provide examples of real lab result. Who will do this?
    • Jamie offered to some, Rachel, May, Bret, other will help.
    • Bret: just take relevant pieces from report, don't do the whole report
  • Rachel: I was going to suggest we state on the flag field "if empty, will be treated as X" and that way the most common option in a context could be defaulted without having to explicitly send a value?

  • Bob F: to Rachel: I'd prefer to require messages be explicit. Too much room for mistaken assumptions on missing data...
  • Arthur: I will work on this, with Jaime, and Rachel, Brett and others.... let's figure out offline who needs to get together to provide examples. 
My apologies, but could someone point me to where we store our reports?
  • Rachel will help coordinate with Arthur.
  • Kevin: start this on zulip
  • Rachel: Can we explicitly state the goal of this?

  • Bret: suggest to have a call. Arthur agrees.
    • Bret will organize
  • Jamie: https://chat.fhir.org/#narrow/stream/179197-genomics/topic/Stress.20Testing.20IG.20Implications.20with.20Examples 
  • Arthur: will recruit clinicians to provide input
  • May: will share with oncologist


  • Motion: (no motion) 
    • Move / 2nd:  /   
    • Discussion:
    • Vote: (Abstain / Opposed / In Favor):     /   /  
    • Result:  

BELOW NOT DISCUSSED

Topic 4: appropriate way to structure our 'additional text' extension?

FHIR-20978 - Ability to include interpretation text/findings and recommendations to Observation (Mullai Murugan) 

"As highlighted in the attached test reports, we include textual findings/interpretations and recommendations in a genetic report. For the eMERGE reports, while mapping to draft CG IG spec, these textual interpretations span multiple FHIR Observation profiles in our implemention e.g. Referencing file "highlighted..." test report, text highlighted in grey and yellow would be a fit for general profiles like obs-overall and obs-inh-dis-path; text highlighted in green would be a fit for PGx profiles and the recommendations text highlighted in blue is a recommendation for the provider but not exactly a recommended action; it would be up to the provider to decide on the recommended action.

Considering the need for including this kind of interpretative/summary text (this is not the same as the "text" narrative element) spans multiple Observation resources, it would be very helpful if Interpretation Text and Recommendations were added as Narrative or String elements to the obs-base resource itself."

Resolution: Analysis in Progress

"Resolution Description:
Next steps: look through requested extensions from use cases and get a short list of where they need to go so we can draw clear lines between method.text, component.interpretation, etc.

Previous proposal

Add a new complex Extension (AdditionalGuidance) (0..*), with two attributes:


  • type (CodeabeConcept), binding = example, unbound
  • content (Annotation)


Associate extension to GenomicsBase profile, making it available on any Observation profiles."


**From Tuesday Apr 14:
Next steps: look through requested extensions from use cases and get a short list of where they need to go so we can draw clear lines between method.text, component.interpretation, etc.**

  • Discussion
  • Motion: ? 
    • Move / 2nd:  /   
    • Further Discussion:
    • Vote: (Abstain / Opposed / In Favor):     /   /  
    • Result:  

Topic 5: how to link to region studied?

FHIR-24598 How to reference a region studied observation from genotype, haplotype, variant observations (Bob Milius)

"I have a DR with multiple result (Observations). Each Observation could have different Region Studied. While I can add each Region Studied to the DR, this doesn't allow me to associate a specifc Genotype/Haplotype/Variant to a specific region studied. I'm looking for guidance how to do this. Observation.derivedFrom? I used to be able to use a component for "Description of ranges of DNA sequences examined".

  • Discussion:
    • Bob M: There is a lack of documentation around how to use region-studied at different levels. Is it only at the DR?  I understand that observation.component[gene-studied] allows me to see what found, and that region-studied tells me what was looked for, and that mostly answers my question. But I use gene-studied as a qualifier for Genotype or Haplotype observations. It tells me that I'm reporting a genotype (or haplotype) for a particular gene. So it's telling me not only what found, but also what was looked for. Basically I'm looking for more specific guidance on how to associate what was looked for for each separate observation. 
  • Motion: ? 
    • Move / 2nd:  /   
    • Discussion:
    • Vote: (Abstain / Opposed / In Favor):     /   /  
    • Result:  

Topic 6: Uncallable subregions in a region studied

FHIR-25296 Uncallable subregions in a region studied (Bob Dolin)

 "Would like to consider a new 'no call region' component for the region-studied profile. With this component, in response to a query for variants in a given region, a server can provide a report that also enumerates non-callable subregions, potentially enabling one to differentiate non-callable vs. true negatives.

 

(The main use case we based this on was the need to include wildtype variant calls for PharmGKB's PharmCAT (https://github.com/PharmGKB/PharmCAT) software).

 

The attached example is a set of variants found for 1000 Genomes patient HG00403 in range chr1:1000000-1100000 that includes non-callable subregions. (It's based on a slightly outdated pre-publication version of the IG)."

  • Discussion:
  • Motion: ? 
    • Move / 2nd:  /   
    • Discussion:
      •    
    • Vote: (Abstain / Opposed / In Favor):     /   /  
    • Result:   



Chat

From Rachel Kutner (Epic) to Everyone:  10:38 AM

My understanding based on reports I've seen is that there can be a difference between diagnostic associated disease and associated phenotypes based on Germline testing

That, for example, a variant may be resulted with "Positive for Lynch Syndrome" which then has associated increased risk for different cancers

and there will be variant-specific information detailing beyond just the syndrome information with study-specific information that is unique to the variant detected

From Rachel Kutner (Epic) to Everyone:  10:45 AM

I like the idea of flagging information to make the context clear

From Bob F to Everyone:  10:48 AM

Flags work when there are a small and finite number of terms. Are there examples of both of those terms being used together? Could other terms be added in the future? Perhaps we should consider a value set.

From Rachel Kutner (Epic) to Everyone:  10:50 AM

I was going to suggest we state on the flag field "if empty, will be treated as X" and that way the most common option in a context could be defaulted without having to explicitly send a value? 

From Bob F to Everyone:  10:51 AM

Rachel: I'd prefer to require messages be explicit. Too much room for mistaken assumptions on missing data...

From Arthur Hermann to Everyone:  10:54 AM

I will work on this, with Jaime, and Rachel, Brett and others.... let's figrure our offline who needs to get together to provide examples

My applogies, but could someone point me to where we store our reports? 

From Kevin Power to Everyone:  10:55 AM

Example reports https://drive.google.com/drive/folders/18T4RS0VnrJdLS3k79skbrZ0cYyL1U53t

From Rachel Kutner (Epic) to Everyone:  10:58 AM

Can we explicitly state the goal of this?

From James Jones to Everyone:  10:59 AM

https://chat.fhir.org/#narrow/stream/179197-genomics/topic/Stress.20Testing.20IG.20Implications.20with.20Examples

Future Topics

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 

https://loinc.org/93044-6/

https://loinc.org/LL5356-2/

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: 

E.g. from http://build.fhir.org/ig/HL7/genomics-reporting/Bundle-oncologyexamples-r4.xml

(note, this example uses placeholder value “AMP Guidelines” instead of a tier)

Profile: http://build.fhir.org/ig/HL7/genomics-reporting/somatic-predictive.html

Code: somatic-predictive (TBD LOINC)

Value: E.g. Resistant, Responsive, Not-Responsive, Sensitive, Reduced-Sensitivity, Adverse Response

Component: Level of evidence - 

Code: 93044-6, 

Value: from LOINC Answer List LL5356-2 (preferred) CAN USE TIER SYSTEM HERE

Component: medication

Component: cancer

  • 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 -  / /

       Result - 

Need to create an example to understand the meaning of this change/concepts.
Need a caretaker for this topic.



Clinical Genomics Reference Docs

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