alhenry / fractalgenetics

Analysis of the genomic architecture and functional role of myocardial trabeculae

Genetically-determined fractal properties of heart muscle are crucial to cardiovascular function

The endocardial surface of the adult human hearts consists of a complex network of muscular trabeculae. Thought to be a remnant of embryonic development, it remains uknown why these complex structures still persistent in the adult organ. Here, we use population genomics, image-based intermediate phenotyping and in silico modelling to determine the effect of this complex cardiovascular trait on function.

The full study is available on BioRxiv.

The following repository contains all data analysis and processing scripts applied in the study.

Software requirements

Data processing and analysis is embedded into different snakemake (v5.1.5) workflows. Genetics analyses require plink v1.9 and v2 as well as flashpca. Data visualisation and processing is done in R, version 3.6.1. Genetic association testing requires Bgenie v1.3. Fractal analysis requires Matlab, MATLAB Compiler Runtime (MCR) 2016b and Ghostscript. Finite element modeling was conducted with Abaqus/Standard, Simulia.

Content

1. Automated-fractal-analysis

Automated fractal analysis of segmented cardiac images using pre-exisiting image segmentations to determine a region of interest within the myocardium.

2. Fractal-analysis-processing

Code for post-processing of fractal-analysis results including interpolation of FD values to a common number of slices across individuals, summary statistics of FD values per individual and a collection of functions for co-registration of myocardial and trabeculation outlines.

3. UK-Biobank

Trabeculation GWAS in UK Biobank containing analysis pipelines for genotype and phenotype processing, GWAS, GWAS results processing, functional enrichement, Mendelian randomisation analyses and LDhub analyses in discovery and replication study.

4. UK Digital Heart Project

Trabeculation GWAS in the UK Digital Heart Project cohort (second replication cohort) containing analysis pipelines for genotype and phenotype processing, GWAS and GWAS results processing.

5. Finite element modelling

Finite element modeling input files (Abaqus Standard, SIMULIA, Dessault Systemes)for the simulation of 5 consecutive cardiac cycles of the left ventricle, starting from the ventricular reference configuration (zero ventricular pressure).