toward interactive visual tools for comparing phenotype profiles
DESCRIPTION
Monarch Initiative presentation on the phenogrid visualization tool, presented during the 2014 Phenotype Day workshop held by the BioOntologies SIGTRANSCRIPT
Toward interactive visual tools for comparing phenotype profilesCharles Borromeo, Jeremy Espino, Ncole L. Washington, Maryann Martone, Christopher J. Mungall, Melissa A. Haendel, Harry Hochheiser
Goal: Visually compare patient phenotypes across species
2
▪ Ontological similarity of phenotype profiles within human and across taxa can inform diagnosis and identify models
!▪ Challenge: interpret
correspondences between input phenotypes and matches within and across species
How do models recapitulate disease?
3
b2b1035Clo (aka Blue Meanie)
b2b012Clo (aka Heart Under Glass)
Fgfr2
Fuzb2b1273Clo (aka octomouse)
Duplex kidney Cleft palate Prenatal growth retardation Tricuspid valve atresia Persistent truncus arteriosis Double outlet right ventricle Anophthalmia Microphthalmia Kidney cysts Pulmonary valve atresia Polycystic kidney Ventricular septal defect Common atrium Atrioventricular septal defect Complete atrioventricular septal defect ……
Cleft palate Abnormal sternum morphology Double outlet right ventricle Polydactyly Pulmonary hypoplasia Kidney cysts Duplex kidney Right aortic arch Common atrium Complete atrioventricular septal defect Pulmonary artery atresia
Why is visualization needed?4
Human phenotypes!p1!
.!
.!
.!pn
Model 1 phenotypes!m1,1!
.!
.!
.!m1,j
Model m phenotypes!mm,1!.!
.!
.!mm,k
n input phenotypes!m models!!O(nm) comparisons!!O(102) phenotypes !!O(103) models
Need a dense display!to facilitate comparisons !and !access details..
Questions and Challenges5
Patient phenotypes Which input phenotypes are well-covered across multiple models?
Which phenotypes are not frequently recapitulated?
.. and might therefore be particularly useful for diagnosis?
Which model diseases are most similar?
Models
Which models are most similar to an input phenotype profile?
Which models are similar to each other?
… and how do they differ?
How do different types of models compare?
Mouse, zebrafish, fly….
Known diseases, other patients?
Relationships Why is a given input phenotype similar to a model phenotype?
PhenoGrid Overview display6
Top matches for human, mouse, and zebrafish
Human disease comparisons7
Comparison with mouse genes8
Demo…9
Implementation Details
Monarch-app (Middleware)
NIF architecture and data services
Client
Server
jQuery D3
HTML5
Phenogrid Widget
jQuery widget suitable for integration into 3rd party sites
Code:! ! ! ! ! http://www.github.com/monarch-initiative/monarch-app!Deployment instructions:! http://www.monarchinitiative.org/page/phenogrid
Next steps…11
Detailed explanation of phenotype similarity results
Additional comparisons: phenotype profile against other patients, or all orthologs of a given gene
comparing subtypes of a disease
Contributions of individual phenotypes? What if I remove the phenotype?
Additional next steps.. 12
Add other data sources: proteins, pathways, etc.
!Choose profiles to compare
!Hierarchical display of phenotypes.. use ontology structure.
!Integrate other data network views
Acknowledgements13
LBNL
¤ Chris Mungall
¤ Suzanna Lewis
¤ Nicole Washington
!OHSU
¤ Melissa Haendel
!NIH – UDP
¤ Neal Boerkoel
Charité / HPO ¤ Peter Robinson ¤ Sebastian Kohler !Sanger / Exomizer ¤ Damian Smedley
!UCSD / NIF ¤ Maryann Martone
!University of Pittsburgh ¤ Becky Boes
¤ Charles Borromeo
Funding: NIH Office of Director: 1R24OD011883 NIH-UDP: HHSN268201300036C
http://www.monarchinitiative.org