Illumina Inc. has introduced PromoterAI, a deep learning algorithm that identifies disease-causing regulatory variants in the noncoding regions of the human genome—specifically promoter regions. This innovation is poised to significantly improve rare disease diagnosis rates, especially where traditional exome sequencing falls short.
The Diagnostic Challenge: Unseen Variants in Noncoding DNA
1. Current Limitations in Rare Disease Diagnostics
- Only ~30% of rare disease patients currently receive accurate diagnoses from exome sequencing.
- Over 98% of the human genome is noncoding, yet it remains largely unexplored in clinical diagnosis.
2. Role of Promoters in Gene Expression
- Promoters are crucial noncoding elements that determine where gene transcription begins.
- Mutations in promoters can impair gene expression, even if the gene itself remains unaffected.
PromoterAI: Core Capabilities and Scientific Foundation
1. Deep Learning Applied to Whole-Genome Sequencing
- PromoterAI uses cutting-edge neural networks to interpret promoter regions at scale.
- Enhances WGS analysis by flagging promoter variants linked to disease pathogenesis.
2. Insights from the Science Publication
- Recent research published in Science shows that up to 6% of rare diseases may be linked to promoter mutations.
- PromoterAI detects these with high accuracy, providing researchers with new avenues for diagnosis.
Combined Power: PromoterAI with Other AI Tools
1. AI Tools in Illumina’s Portfolio
- SpliceAI (2019): Detects cryptic splice site mutations.
- PrimateAI-3D (2023): Predicts impact of protein-coding variants using structural and evolutionary data.
- PromoterAI (2024): Adds a regulatory variant detection layer to enhance diagnostic depth.
2. Multiplicative Effect
- Combining PromoterAI with SpliceAI and PrimateAI-3D doubles diagnostic yield compared to protein-truncating variant analysis alone.
Accessibility and Integration
1. Availability and Use
- PromoterAI is now integrated into Illumina Connected Software and DRAGEN™ secondary analysis pipelines.
- Precomputed PromoterAI scores for all human promoter SNVs are available for academic and noncommercial use.
2. Workflow Compatibility
- Seamless integration with next-gen sequencing and multiomics workflows.
- Enables researchers, clinical geneticists, and bioinformaticians to prioritize high-impact variants.
Leadership Insights
Kyle Farh, MD, PhD – VP, Illumina AI Lab
“PromoterAI holds the power to improve the rate of rare disease diagnosis by identifying previously overlooked variants in the noncoding genome.”
Rami Mehio – VP, Software and Informatics
“PromoterAI exemplifies our commitment to delivering predictive accuracy and valuable insights to accelerate precision medicine.”
With the launch of PromoterAI, Illumina continues to push the boundaries of AI in genomics. By focusing on noncoding regions, particularly promoters, the company enables deeper insights into the underlying causes of rare diseases—transforming how clinical researchers approach diagnosis and therapy development. Integrated into Illumina’s powerful software ecosystem, PromoterAI is a breakthrough for personalized medicine and rare disease research.
