Illumina 5-base sequencing resolves complex central nervous system cancers and rare and undiagnosed genetic diseases

Poster Abstract: Ev Chekalin1, Areeba Patel2, Bekim Sadikovic3, Michaela-Kristina Keck2, Jennifer Kerkhof3, David Jones2, Suzanne Rohrback1, Eric Brustad1, William Jordan1, Oscar Murillo1, Danielle Goldberg1, Emily Parker1, James Baye1, Joshua Beytebiere1, Kayla Busby1, Bridget Dorsey1, Sophie Fertel1, Stephen Gross1, Rebekah Karadeema1, Huy Lam1, Valerie Montel1, June Pais1, Angelica Schalembier1, David Tse1, Kat Tzeng1, E. Puffenberger4, K. Brigatti4, D. Basel5, J. McCarrier5, Michael Levy3, Seyyedeh Sadegheh Haghshenas3, Allison Yunghans1, Helge Lubenow2, Fiona Kaper1, Lisa Watson1

Abstract

Purpose:

• Multiomic approaches provide predictive insights into the phenotypes of biological systems. For example, in glioblastoma profiling, both SNVs in EGFR and MGMT promoter methylation are prognostic biomarkers that inform treatment decisions. In genetic disease, imprinting disorders require both genome and DNA methylation analyses to identify pathogenic changes. However, multiomic approaches are often time-consuming, and require considerable material input, presenting a significant barrier to widespread adoption.

• Illumina 5-base DNA Prep a novel single-step methyl-conversion method and DRAGEN analysis that enables detection of both genomic variants and DNA methylation from a single workflow

• We paired Illumina 5-base Prep paired EpiSign classifiers and Emedgene variant analysis to evaluate 3 RUGD disease case previously resolved through separate methylation and WGS assays.

• Additionally, we combined Illumina 5-base Prep with tumour classification algorithms powered by Epignostix CNS tumor classifier to assess central nervous system (CNS) tumour samples that have previously been classified through methylation array.

• We demonstrate that Illumina 5-base Prep with DRAGEN analysis and EpiSign and Epignostix classifiers resolve multiomic RUGD and CNS cases with a single workflow.