MERCURIUS™ 1536 DRUG-seq Generates Reproducible Ultra-High-Throughput Transcriptomic Perturbation Datasets That Decipher Compound Mechanisms of Action and Toxicity Pathway Activation 

In this whitepaper, Alithea Genomics demonstrates the performance of MERCURIUS™ 1536 DRUG-seq, an ultra-high-throughput, RNA-extraction-free 3′ mRNA-seq technology designed to generate transcriptomic perturbation datasets at screening scale.

Arctoris contributed automated experimental execution using the Ulysses® platform, automating key steps including compound plate preparation, cell dispensing, viability assessment, plate handling and downstream processing.

The study demonstrates highly reproducible transcriptomic profiling across independently processed plates, with over 12,000 genes detected per sample and strong concordance in differential gene detection and dose-response profiles (R² = 0.94). The data also enabled compounds to be grouped by known mechanisms of action and revealed compound-specific pathway responses, including toxicity-associated signatures.

Download the whitepaper to discover:

• How MERCURIUS™ 1536 DRUG-seq enables whole-transcriptome profiling in 1536-well format
• How automated experimental execution with Ulysses® supports reproducible high-throughput transcriptomic workflows
• How over 12,000 genes can be detected per sample from just 800 HepG2 cells
• How transcriptomic profiles can resolve compounds by mechanism of action and toxicity-associated pathways
• How gene-level analysis can distinguish mechanistic differences between compounds with the same overall MoA
• How transcriptomic responses can provide earlier insight into cellular stress than conventional viability endpoints alone
• How reproducible dose-response profiles and transcriptomic points of departure (tPODs) can be generated across independently processed plates
• How combining transcriptomic and conventional viability readouts can provide a more comprehensive view of compound response