Data analytics for better patient genetics

Herman Verrelst

CEO

26-March-2013

Genetic diagnosis of patients with developmental anomalies

Clinical Cytogenetics

genomic DNA microarrays

band stain karyotyping

Medical genetic diagnosis

04/11/23 4

Technology push

04/11/23 5

Towards the $ 1,000 genome

Interpretability of Genomic Data

# Genetic data

Complexity

Price pbp

Interpretability

Analysis bottleneck

04/11/23 8

04/11/23 9

Full exome analysis

Patient: female, 8yr

severe obesity

Whole exome triopatient, 29183 variants

mother, 35541 variants

father, 34764 variants

04/11/23 10

Information sources to consult…

Quality informationRead depth, PHRED scores, confidence, mapping, …

Protein and functional variant annotation

ANNOVAR, Mutalyzer, Alamut, MutationTaster, …

Disease lists and Gene functionOMIM, GeneReviews, PUBMED literature, functional studies, …

DECIPHER syndromes, known disease variants, …

Variant databases1000 genomes, exome data sets, dbSNP, LSDBs

HGMD, ClinVar, ISCA, DGV, …

04/11/23 11

Splice site prediction tools SpliceSiteFinder, HSF, GeneSPlicer, …

Effect prediction tools polyphen, SIFT, …

Conservation prediction toolsPhastCons, PhyloP, GERP, AGVGD, …

Genotype-Phenotype correlations London databases LDDB, Human Phenotype Ontology OMIM links, …

Patient registries, GWAS studies, research cohorts, …

Internal databasesFamilies, variant lists, excel, access, files, databases, lists, validated findings, …

Standard of care

Need to consult broad / public consensus body of knowledge in routine diagnostics

Need to contribute to pool genomic variation and clinical relevance / consequence

International / researchgenome variation

databases

Collaborative Local Community

Pooling initiatives

Lab - localgenome variant

libraries

CONFIDENTIEEL04/11/23

Genetic CNV mutation atlas

Min. freq. = 1

Min. freq. = 2

Min. freq. = 3

Min. freq. = 4

Min. freq. = 5

Most narrow common region

Lab A, Patient 1

Lab C, patient 4

Lab B, Patient 2

Lab D, Patient 5

Lab A, Patient 3

A revolution in the clinic

Pathology domains & clinical expertise:Pathology domains & clinical expertise:

NeonatologyNeonatologyOrthopedicsOrthopedics PediatricsPediatricsGynecologyGynecology

DentalDental ImmunologyImmunologyObstetricsObstetrics Prenatal diagnosisPrenatal diagnosis

GastroenterologyGastroenterology Neuro-pediatricsNeuro-pediatricsENTENT NeurologyNeurology

OphthalmologyOphthalmologyCardiologyCardiology FertilityFertilityChild psychiatryChild psychiatry

PneumologyPneumologyOncologyOncology Metabolomic diseasesMetabolomic diseases ……

100s, 1000s or even millions of

variants

Cartagenia delivers diagnostic knowledge, systems and services to enable genetics labs and clinicians to perform clinically relevant genetic analyses quickly

and efficiently, and offer high quality genetic interpretation and counseling to patients and care providers.

Cartagenia delivers diagnostic knowledge, systems and services to enable genetics labs and clinicians to perform clinically relevant genetic analyses quickly

and efficiently, and offer high quality genetic interpretation and counseling to patients and care providers.

Molecular variationStructural variation

&