Epigenomic insights into common human disease pathology
1William Harvey Research Institute, Barts & The London Faculty of Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK. c.bell@qmul.ac.uk.
Cellular and Molecular Life Sciences : CMLS
|April 11, 2024
Summary
The epigenome regulates gene activity for cell function and development. Epigenomic changes are crucial in diseases like cancer, offering new therapeutic targets.
Area of Science:
- Epigenetics and Molecular Biology
- Genomics and Bioinformatics
- Disease Pathogenesis and Biomarkers
Background:
- The epigenome, comprising chemical modifications and chromatin packaging, dictates gene expression for cellular identity and function.
- Precise installation and maintenance of the epigenome are vital for development and lifespan.
- Mutations in epigenomic machinery genes are implicated in cancer and developmental disorders, highlighting the epigenome's causal role in pathology.
Purpose of the Study:
- To explore the expanding role of the epigenome in human health and disease.
- To discuss advancements in understanding epigenomic alterations and their implications.
- To highlight the potential of epigenomic insights for diagnostics and therapeutics.
Main Methods:
- Analysis of large-scale sequencing data to identify mutations in epigenomic machinery genes.
- Generation of cell-type specific reference epigenomes by consortia.
- Application of high-throughput DNA methylome association studies and machine learning for biological 'clocks'.
- Utilizing 3rd-generation sequencing to analyze genetic and DNA modification haplotypes.
- Investigating cell-free DNA methylation as a biomarker.
Main Results:
- Epigenomic machinery gene mutations are critical drivers in cancer and developmental disorders.
- Consortia-generated reference epigenomes and DNA methylome studies advance disease mechanism understanding.
- Machine learning-derived biological 'clocks' provide insights into aging-related diseases.
- Cell-free DNA methylation shows clinical utility as a cancer biomarker and for organ damage assessment.
- 3rd-generation sequencing aids in disentangling complex genetic and epigenetic haplotypes.
Conclusions:
- Deciphering epigenomic changes is challenging but crucial for understanding disease aetiology.
- Epigenomic knowledge is advancing disease mechanism insights and biomarker discovery.
- Therapeutic strategies targeting the epigenome, such as CRISPR-activation/inhibition, are emerging.
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