Predicting the effects of noncoding variants in Human Cardiac Disease

Towards A Future With Millions Of Human Genomes Sequenced

IQCC Science Slam, Girona, 24/11/2016 – Research Project by Sara Pagans & Miquel Duran

The Challenges• We Know the Letters, We Do Not Know Most of the Words, We Do

Not Understand Most of the Sentences

• There Is Not A “Single” Human Genome, Every Person Has His/Her Own Genome

• There is a Coding Fraction in the Genome that We Understand, But Only Represents 1-2% Genome

We Are Trying to Understand the Meaning of Noncoding Words and Sentences

Many ‘Words’ Have Meaning Regarding Transcription Factors Binding and Binding Strenght

Correct gene expression is very important for human biology.

Model System of Our Analyses: Cardiac Cells and Sudden Cardiac Death

• Sudden stop of heart beating without any previous symptoms. • 800,000 deaths occur annually in the Western World.• Mainly affects men in their 40’s or younger and kids/babies.

112Emergency!!

Brugada Syndrome: High Risk of Sudden Cardiac Death

70-75%Unknown cases.

Genetic variants outside genes?

89 BrS patients

SequencingCapturing of 1,298 TF binding sites

(0,03%)

6,589 Genetic Variants in only 0,03% of the Human Genome.

Sequencing 1,298 Transcription Factor Binding Sites in 89 BrS Patients

30% individual-specific 70% shared among all 89 BrS patients

Computational tools based on machine learning: Deep Bind

Which Variants are Functionally Relevant in Disease?

Interpreting Non-Coding Variants to Predict the Risk of Brugada Syndrome

89 BrS patients

Catalogue of VariantsAssociated to Brugada Syndrome

Social Impact: We Will Be Able to Predict the Risk of Disease

Variant 1 + Variant 3 + Variant 100 + … = Cardiac DiseaseVariant 5 + Variant 7 + Variant 50 + … = AlzheimerVariant 52 + Variant 67 + Variant 200 + … = Breast Cancer

Whole Genome Sequence

Role of IQCC: experience on high-performance computing, on efficient use of network resources, on applications. Computers & (bio)chemistry.

IDIBGi - UdGDr. Sara Pagans (IP)Dr. Elisabet SelgaDr. Mònica CollMel·lina PinsachBernat del OlmoJesús MatésIQCC-UdGDr. Miquel Duran (co-IP)Overall coordination:Dr. Ramon Brugada (IDIBGI-UdG)Funding: MINECO

The Project Team