B Institute of Bioinformatics in Brussels Improve clinical - - PowerPoint PPT Presentation

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Oct 05, 2022 231 likes •357 views

Interuniversity 2 B Institute of Bioinformatics in Brussels Improve clinical diagnosis of rare genetic disorders with GEMVAP a GE ne-specific M issense VA riant P redictor framework Marfan Meeting 5 th of October 2019 Pr Guillaume Smits, MD

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Improve clinical diagnosis

f rare genetic disorders with GEMVAP

a GEne-specific Missense VAriant Predictor framework

Pr Guillaume Smits, MD PhD Marfan Meeting 5th of October 2019

B

Interuniversity Institute of Bioinformatics in Brussels

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Missense variant interpretation is challenging

DNA HAS ALL YOU CAN ASK FOR . DNA HAS ALL YOO CAN ASK FOR . DNA HAS ALL YOU . DNA HAS ALY OUC ANA SKF OR. DNA HAS ALL LOU CAN ASK FOR .

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Predictors evaluate the pathogenicity of variants

Predictor 1 Predictor 2 Predictor 3 Variant 1 Damaging Pathogenic Damaging Variant 2 Neutral Pathogenic Damaging Variant 3 Neutral Benign Neutral

. . . . . .

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From gene-agnostic variant predictors...

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…to a gene-specific variant predictor

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The GEMVAP framework

Gene A

Dataset of Control variants

Gene A

Dataset of Patient variants

Set of Predictors

GEMVAP

Gene A

Dataset of Control variants

Data processing

Statistical Methods

Consensus

Gene A specific variant prediction

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Collection of FBN1 datasets

Pathogenic Intersection Control Size 1868 188 976

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Tolerance of FBN1 amino acids to mutation

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TopN predictors for each training set

Missense Missense & Cysteine Cysteine

5 5 17 17 3 3

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GEMVAP FBN1 top5 predictors model

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GEMVAP FBN1 top5 whole gene prediction

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Acknowledgements

Romain & Ludivine Alderweireldt-Verboogen
Bart Loeys & Aline Verstraeten, UAntwerp
Julie De Backer & Paul Coucke, UGent
Catherine Boileau & Guillaume Jondeau, Bichat Paris
Claudio Reggiani & Youssef Bouysran

B

Interuniversity Institute of Bioinformatics in Brussels