Improving Infinium MethylationEPIC data processing: re-annotation of enhancers and long noncoding RNA genes and...

Area of Science:

• Epigenetics and Genomics
• Cancer Research
• Bioinformatics

Background:

• Illumina Infinium DNA Methylation arrays (5mC) are widely used for genome-scale 5mC profiling.
• The MethylationEPIC array (850k) offers enhanced coverage but suffers from suboptimal analysis due to default annotation.
• Existing annotation underestimates enhancers and long noncoding RNAs.

Purpose of the Study:

• To develop an improved annotation and analysis approach for Illumina's 850k DNA Methylation array data.
• To enhance the detection of enhancers and long noncoding RNAs in methylation studies.
• To refine the understanding of DNA methylation patterns in complex diseases like cancer.

Main Methods:

• Developed a novel annotation approach using ENCODE and LNCipedia databases for 850k array data.
• Compared the re-annotated 850k array with 450k arrays and reduced-representation bisulphite sequencing (RRBS).
• Applied various normalization methods to 850k data to assess reproducibility.

Main Results:

• The new annotation significantly increases the coverage of enhancers and long noncoding RNAs compared to 450k and RRBS.
• Normalization methods improved 850k data reproducibility, often surpassing RRBS levels.
• Analysis of breast cancer biopsies using the refined 850k approach revealed aberrant enhancer methylation as a key feature.

Conclusions:

• The developed approach provides an updated, optimized processing strategy for 850k DNA Methylation array data.
• Refined annotation and normalization enable more accurate analysis of methylation at enhancers and long noncoding RNA genes.
• This advancement facilitates a deeper understanding of the DNA methylome in both health and disease contexts.