toward interactive visual tools for comparing phenotype profiles

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Toward interactive visual tools for comparing phenotype profiles Charles Borromeo, Jeremy Espino, Ncole L. Washington, Maryann Martone, Christopher J. Mungall, Melissa A. Haendel, Harry Hochheiser

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Monarch Initiative presentation on the phenogrid visualization tool, presented during the 2014 Phenotype Day workshop held by the BioOntologies SIG

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Page 1: Toward interactive visual tools for comparing phenotype profiles

Toward interactive visual tools for comparing phenotype profilesCharles Borromeo, Jeremy Espino, Ncole L. Washington, Maryann Martone, Christopher J. Mungall, Melissa A. Haendel, Harry Hochheiser

Page 2: Toward interactive visual tools for comparing phenotype profiles

Goal: Visually compare patient phenotypes across species

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▪ 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

Page 3: Toward interactive visual tools for comparing phenotype profiles

How do models recapitulate disease?

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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

Page 4: Toward interactive visual tools for comparing phenotype profiles

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..

Page 5: Toward interactive visual tools for comparing phenotype profiles

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?

Page 6: Toward interactive visual tools for comparing phenotype profiles

PhenoGrid Overview display6

Top matches for human, mouse, and zebrafish

Page 7: Toward interactive visual tools for comparing phenotype profiles

Human disease comparisons7

Page 8: Toward interactive visual tools for comparing phenotype profiles

Comparison with mouse genes8

Page 9: Toward interactive visual tools for comparing phenotype profiles

Demo…9

Page 10: Toward interactive visual tools for comparing phenotype profiles

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

Page 11: Toward interactive visual tools for comparing phenotype profiles

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?

Page 12: Toward interactive visual tools for comparing phenotype profiles

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

Page 13: Toward interactive visual tools for comparing phenotype profiles

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

Page 14: Toward interactive visual tools for comparing phenotype profiles

http://www.monarchinitiative.org