Benchmarking Methods for Identifying Causal Mutations
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Benchmarking Methods for Identifying Causal Mutations Tal Friedman
description
Benchmarking Methods for Identifying Causal Mutations. Tal Friedman. Rare Genetic Diseases. Our goal: identify and diagnose rare genetic diseases Difficult for clinicians due to incredibly low exposure Often not already documented. PhenomeCentral. Clinicians upload patient data. - PowerPoint PPT Presentation
Transcript of Benchmarking Methods for Identifying Causal Mutations
Benchmarking Methods for Identifying Causal MutationsTal Friedman
Rare Genetic Diseases
•Our goal: identify and diagnose rare genetic diseases
•Difficult for clinicians due to incredibly low exposure
•Often not already documented
PhenomeCentral
• Clinicians upload patient data
PhenomeCentral
•Matchmaking algorithm displays most similar patients
•Get additional evidence from other clinicians
Background
• Phenotype: Observable characteristics
•Human Phenotype Ontology (HPO)
Robinson et. al
Exomiser
(Robinson et. al, 2014)
Objectives
• Reproduce Exomiser performance
• Expand to new patient similarity domain
Patient Simulation
Control Genome
Mutation
HPO Terms
Infected Patient
Disease
Results
Series10
100
200
300
400
500
600
700
371
547
659
# of causal genes as top hit (N=999)
First attemptSecond attemptExomiser reported
Patient Similarity
• Phenotypic similarity algorithm
•Hypothesis: same disease/causal gene
• Combine Exomiser results
Patient Pair Simulation
Control Genome A
Sampled mutation
Sampled HPO terms
Patient 1
Control Genome B
Sampled mutation
Sampled HPO terms
Patient 2
Disease
Phenotypic Noise & Imprecision
Phenotypic Noise & Imprecision
Results (preliminary)
Series10
100
200
300
400
500
600
700
800
900
397483
768
# of causal genes as top hit (N=890)
ExomiserAveragingPhenomeCentral
Challenges
•Data
•Data
•More data
ChallengesROC Curve for Phenotypic Similarity Algorithm
Questions!
