Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

ABSTRACT: Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific d

SUBMITTER: Levy MA 

PROVIDER: S-EPMC8756545 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature