Automated Sequential Protein/DNA/RNA Extraction Workflow for Multiomics Analysis

Introduction: The integration of proteomics, genomics, and transcriptomics is crucial for comprehensive biological insights. We have developed an automated sequential Protein/DNA/RNA workflow designed to reproducibly isolate high-quality protein, DNA, and RNA from the same sample using the KingFisher™ SamplePrep Purification System, enhancing the efficiency, through-put and depth of multiomics studies. Methods: Our sequential Protein/DNA/RNA extraction workflow utilizes a magnetic bead-based approach, leveraging the well renowned Dynabeads™ and MagMAX™ magnetic beads technologies. This enables efficient isolation of protein, DNA, and RNA from as few as 1,000 cells or 1 mg of tissue. The workflow is compatible with both manual and automated processing on the KingFisher™ sample purification system, accommodating a wide range of sample numbers from low to high throughput. Results: • Mass Spectrometry (MS): The workflow produces high-quality proteins suitable for MS analysis. Comparative studies with the EasyPep™ MS Sample Prep Kit show similar chromatograms, peptide properties, and distribution profiles among biological processes and cellular components, as well as absence of incompatible reagents. • Next-Generation Sequencing (NGS): The workflow yields high-quality nucleic acids compatible with NGS. Whole genome sequencing and rRNA depletion sequencing demonstrate excellent molecular depth, coverage and uniformity, with robust QC metrics across various sample types. Conclusion: The sequential Protein/DNA/RNA workflow offers a versatile and efficient solution for multiomics research, providing high-quality analytes compatible with both MS and NGS. This magnetic bead-based workflow, utilizing Dynabeads™ and MagMAX™ magnetic beads, is ideal for precious and small samples, enabling reproducible data and high throughput capabilities. For Research Use Only. Not for use in diagnostic procedures. Citation Format: Laure Jobert, Charmaine Hinahon, Leigh Foster, Marie Holter-Sørensen, Samri Michael, Iwona Grad, Lina Zheng, Berit Reed. An automated sequential protein/DNA/RNA extraction workflow for comprehensive multiomics analysis from cells and tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7664.