*2.2. Library Preparation and Next Generation Sequencing*

In the Care4DCM cohort, the biopsies were retrieved from the LV apex during heart catheterization [8]. The specimen of each patient was immediately washed and preserved in liquid nitrogen according to standardized protocols. After the histopathological work-up, DNA and RNA were extracted from the leftover cardiac tissues using Allprep Kits (Qiagen, Düsseldorf, Germany). In the replication cohort, the DCM hearts were immediately transported and stored after explantation, and the hearts of healthy traffic accident victims were flash-frozen less than three hours after death. Before starting sequencing, a Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA, USA) and a eukaryote total RNA pico assay (Agilent Technologies, Santa Clara, CA, USA) were utilized to examine the purity and concentration of RNA. The sequencing of DNA methylation profiling was carried out using the Infinium HumanMethylation 450K BeadChip kit (Illumina, San Diego, CA, USA). The RNA sequencing was performed with the TrueSeq RNA Sample Prep Kit (Illumina, San Diego, CA, USA) to paired-end reads, unstrandedly in the screening cohort and strandedly in the replication cohort.
