Bioinformatics Seminars

Bioinformatics Seminar

Time: 11AM
Venue: Zoom Webinar

8 March 2022

Predicting new genes involved in heart development and disease from the non-coding genome and spatially resolved transcriptomes

Mirana Ramialison
MCRI / Monash University (ARMI)

1 percent of Australian babies are born with Congenital Heart Disease (CHD), manifesting as anatomical heart defects that are detrimental for the newborn. Despite its prevalence, the aetiology of more than 80% of CHD cases remains unknown, making diagnosis and evaluation of the risk of the disease inheritance difficult. Our team has a long-standing interest in identifying the specific gene sets required for the formation of a healthy heart based on the principle that perturbations in these genes will impair normal development, resulting in anatomical cardiac defects. Thousands of genes are expressed in the heart at any given time point during development, but which of these genes are critical for heart formation and play a significant role in CHD? To address this, we first designed a bioinformatic pipelines to identify novel players in the cardiac gene regulatory network by mining the non-coding genome. We identified a cis-regulatory signature enriched in genes known to play a role in cardiogenesis and used this signature to predict novel genes important for heart development. This first bioinformatic approach offers the prospect of identifying new genes essential for organ development, irrespective of their expression pattern. Second, CHD manifests in structural defects affecting different regions of the heart. In order to identify the genes that are implicated in a specific cardiac malformation, we generated the first spatially resolved map of the murine heart (3D-Cardiomics at and identified synexpression groups expressed in distinct regions of the heart. Altogether, these pipelines allow to unbiasedly uncover novel genetic determinants of the cardiac gene regulatory network.

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