1. Melissa Haendel April 18th, 2016 Force206
Phenopackets: Making phenotype profiles FAIR++ for disease diagnosis and discovery
Findable
Accessible outside paywalls and private data sources
Attributable
Interoperable and Computable,
Reusable, exchangeable across contexts and disciplines
Melissa Haendel
April 18th, 2016
Force206
@monarchinit
@ontowonka

2. Prevailing clinical pipelines leverage only a tiny fraction of the data
POSSIBLE DISEASES
PATIENT EXOME
/ GENOME
PUBLIC GENOMIC DATA
Under-utilized data
PUBLIC PHENOTYPE,
DISEASE DATA
PATIENT PHENOTYPES
PUBLIC ENVIRONMENT,
DISEASE DATA
PATIENT ENVIRONMENT
DIAGNOSIS & TREATMENT

3. It takes an interoperable village to diagnose a rare platelet syndrome
Ranked STIM-1 variant maximally pathogenic
based on cross-species G2P data,
in the absence of traditional data sources
MGI mouse
Stim1Sax/Sax
This was the novel case we solved. The UDP patient had a number of signs and symptoms including various platelet abnormalities. The same heterozygous, missense mutation was seen in 2 patients and ranked top by Exomiser. It had never been seen in any of the SNP databases and was predicted maximally pathogenic. Finally a mouse curated by MGI involving a heterozygous, missense point mutation introduced by chemical mutagenesis exhibited strikingly similar platelet abnormalities.
Phenotypic
profile
N/A
Heterozygous, missense mutation
STIM-1
Heterozygous, missense mutation
STIM-1
Genes
N/A

4. Image credit-https://pixabay
What if we all helped?

5. Biology central dogma Genes + Environment = Phenotypes
The classic G+E=P. But the = has a lot that can be applied to aid the linking.
Standards for encoding and exchanging data
must be up to these challenges.
@ontowonka

6. Standard exchange formats exist for genes … but for phenotypes
Standard exchange formats exist for genes … but for phenotypes? Environment?
Genes
Environment
Phenotypes
NEW
The classic G+E=P. But the = has a lot that can be applied to aid the linking.
GFF
VCF
BED
PXF
@ontowonka

7. Introducing PhenoPackets
It’s exactly what you think it is:
a packet of phenotype data to be used anywhere, written by anyone

8. What does a PhenoPacket look like?
phenotype_profile:
- entity: "person#1"
phenotype:
types:
- id: "HP: "
label: "Small hands"
onset:
description: "during development"
- id: "HP: "
label: "Congenital onset"
evidence:
- types:
- id: "ECO: "
label: ”Traceable Author Statement"
source:
- id: "PMID:1"
title: "age of onset example"
persons:
- id: "#1"
label: "Donald Trump"
sex: "M"
Canonical JSON format
Image credits: upi.com

9. Phenopackets for laypersons
Dry eyes
Developmental delay
Elevated liver function
phenotype_profile:
- entity: ”patient16"
phenotype:
types:
- id: "HP: "
label: ”Alacrima"
onset:
description: ”at birth"
- id: "HP: "
label: "Congenital onset"
evidence:
- types:
- id: "ECO: "
label: ”Traceable Author Statement"
source:
- id: ”
Reeldx, Inspire, patientslikeme, post phenopacket on facebook
Patient registries
Social media
Image credits: ngly1.org

10. If it is alive, it can be PhenoPackaged
Patients & Cohorts
Personalized
Medicine
Rare Disease Diagnosis
Disease vectors
Model Organisms
Drug discovery & Development
Epidemiological Monitoring
Mechanistic Discovery
Biodiversity
Crops
Domestic Animals
Mosquito image from no attribution required
Environmental Monitoring
Genetic Engineering
Some biodiversity images adapted from

11. Phenopackets for journals (using the new JATS extension!)
Each article can be associated with a phenopacket
Each phenopacket can be shared via DOI (or other ID) in any repository outside paywall (eg. Figshare, Zenodo, etc)
Robinson, P. N., Mungall, C. J., & Haendel, M. (2015). Capturing phenotypes for precision medicine. Molecular Case Studies, 1(1), a doi: /mcs.a000372

12. Acknowledgements OHSU Queen Mary College London Lawrence Berkeley
Matt Brush
Kent Shefchek
Julie McMurry
Tom Conlin
Nicole Vasilevsky
Queen Mary College London
Damian Smedley
Jules Jacobson
Lawrence Berkeley
Chris Mungall
Suzanna Lewis
Jeremy Nguyen
Seth Carbon
Charité
Peter Robinson
Sebastian Kohler
RTI
Jim Balhoff
Garvan
Tudor Groza
Alfred Wegener
Pier Buttigieg
Cyverse
Ramona Walls
U of Pittsburgh
Harry Hochheiser
FUNDING: NIH Office of Director: 1R24OD011883; NIH-UDP: HHSN C, HHSN P, Phenotype Research Coordination Network (NSF-DEB )