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 following repository contains all data analysis and processing scripts applied in the study.
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.
Automated fractal analysis of segmented cardiac images using pre-exisiting image segmentations to determine a region of interest within the myocardium.
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.
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.
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).
Meyer HV et al., Genetic and functional insights into the fractal structure of the heart, Nature, 2020, DOI:10.1038/s41586-020-2635-8
McGurk KA et al., https://github.com/ImperialCollegeLondon/trabecular_variants