Illumina unveils PromoterAI, a groundbreaking algorithm to accelerate insights for rare disease diagnosis

Rhea-AI Summary

Illumina (NASDAQ: ILMN) has unveiled PromoterAI, a groundbreaking AI algorithm that accurately identifies pathogenic regulatory genetic variants in noncoding regions of the human genome. According to a study published in Science, this technology discovered regulatory variants in promoter segments that contribute up to 6% of genetic causes of rare diseases.

PromoterAI analyzes noncoding promoter regions, which are crucial for gene transcription and comprise over 98% of the genome. When combined with whole-genome sequencing (WGS), this AI tool could improve rare disease diagnosis rates, which currently stand at only 30% with exome sequencing. The algorithm, together with Illumina's other AI tools (PrimateAI-3D and SpliceAI), effectively doubles the diagnostic yield compared to using protein-truncating variants alone.

The technology is now available through Illumina Connected Software and DRAGEN™ secondary analysis, with precomputed scores freely available for academic and noncommercial research.

Positive

• Revolutionary AI technology that can identify previously undetectable genetic variants in noncoding regions
• Potential to improve rare disease diagnosis rates beyond current 30% success rate
• Combined with other Illumina AI tools, doubles the diagnostic yield compared to traditional methods
• Free access to precomputed PromoterAI scores for academic and noncommercial research

Negative

• None.

Insights

Genomics Technology Expert

Illumina's PromoterAI represents a significant advancement in genomic interpretation, potentially increasing rare disease diagnostic yields by 6%.

Illumina's newly unveiled PromoterAI algorithm marks a significant technological breakthrough in genomic interpretation. This deep learning-based tool specifically addresses a critical gap in rare disease diagnostics by analyzing the noncoding promoter regions of the genome - areas that comprise over 98% of our DNA but have remained largely uninterpretable until now.

The science here is compelling. Currently, exome sequencing (which examines only protein-coding regions) provides diagnoses for approximately 30% of rare disease patients. PromoterAI's ability to identify pathogenic variants in promoter regions could contribute an additional 6% to diagnostic yields - a substantial improvement considering the millions of people worldwide affected by rare diseases.

What makes this development particularly notable is its integration with Illumina's existing AI suite. When combined with their previous tools (PrimateAI-3D and SpliceAI), the company claims diagnostic yield can be doubled compared to using protein-truncating variants alone. This represents a quantum leap in interpretive capabilities.

From a technical standpoint, promoters are crucial noncoding elements that control where gene transcription begins. Mutations in these regions can profoundly affect gene expression, even when the protein-coding sequences appear normal. By deciphering the impact of these variants, PromoterAI opens new diagnostic pathways.

The immediate availability of this algorithm through Illumina Connected Software and DRAGEN analysis, plus free academic access to precomputed scores, should accelerate adoption across research and clinical settings. This strategy reinforces Illumina's position as not just a sequencing hardware provider but an increasingly sophisticated bioinformatics company delivering end-to-end genomic solutions.

New AI algorithm accurately deciphers pathogenic regulatory genetic variants in the noncoding regions of the human genome at scale for the first time

SAN DIEGO, May 29, 2025 /PRNewswire/ -- Illumina Inc. (NASDAQ: ILMN) today unveiled PromoterAI, a new AI algorithm that accurately deciphers pathogenic regulatory genetic variants in the noncoding regions of the human genome. A study published today in Science illustrates how this deep learning technology discovered regulatory variants in noncoding "promoter" segments that contribute up to 6% of the genetic causes of rare diseases. By turning data into insights, this technology is expected to help researchers accelerate new breakthroughs in diagnosis for rare diseases.

Currently, only about 30% of rare disease patients receive an accurate diagnosis from exome sequencing. For many patients, insights may be hidden in what are known as "noncoding regions," which comprise over 98% of the genome and may hold the key to increasing the diagnostic rate.

Promoters are key noncoding elements that define where transcription of a gene begins. When promoters are disrupted by genetic mutations, it can have profound consequences for downstream gene expression. The PromoterAI algorithm interprets the genetic sequence of promoters, thus opening the door to precise diagnoses for more patients with rare diseases.

"Illumina is breaking new ground with this AI technology," said Kyle Farh, MD, PhD, vice president, distinguished scientist, and head of the Illumina Artificial Intelligence Lab. "Combined with whole-genome sequencing, we believe PromoterAI holds the power to improve the rate of rare disease diagnosis by identifying previously overlooked variants in the noncoding genome. One of the challenges of searching for the genetic causes of rare disease is that, even if the protein-coding sequence of a gene is free from variants, mutations in that gene's promoter region can prevent it from being properly expressed."

Built on state-of-the-art deep learning neural networks, PromoterAI brings unprecedented precision to the interpretation of promoter variants. With PromoterAI applied to whole-genome sequencing (WGS) data analysis, clinical researchers are empowered to better understand the etiology and drug target potential for rare genetic diseases, common diseases, and oncology.

PromoterAI is the latest genomic AI algorithmic innovation from Illumina. In 2019, the Illumina Artificial Intelligence Lab released SpliceAI, a deep learning tool for interpreting noncoding cryptic splice mutations. In 2023, Illumina released PrimateAI-3D, which predicts the pathogenicity of protein-coding variants based on evolutionary conservation and protein structure. The study demonstrates that when used together, Illumina's AI classification prediction tools—PromoterAI, PrimateAI-3D, and SpliceAI—effectively double the diagnostic yield compared to using protein-truncating variants alone. 

"PromoterAI is the latest addition to our AI and software portfolio, which has delivered leading quality, prediction accuracy, and comprehensiveness to turn data into valuable insights for our customers," said Rami Mehio, vice president, and global head of Software and Informatics.

PromoterAI will be accessible through Illumina Connected Software and it is available today as part of DRAGEN™ secondary analysis. Precomputed PromoterAI scores for all human promoter single-nucleotide variants are freely available for academic and noncommercial research use. Illumina Connected Software supports seamless integration with next-generation sequencing and array workflows for genomics and multiomics. Researchers, bioinformaticians, and clinical geneticists can use Illumina Connected Software to prioritize variants that are important to a case, gain critical insights, and accelerate their precision medicine dry lab operations.

Use of forward-looking statements

This release may contain forward-looking statements that involve risks and uncertainties. Among the important factors to which our business is subject that could cause actual results to differ materially from those in any forward-looking statements are: (i) challenges inherent in developing, manufacturing, and launching new products and services; (ii) customer uptake of, and satisfaction with, new products and services; and (iii) legislative, regulatory and economic developments, together with other factors detailed in our filings with the Securities and Exchange Commission, including our most recent filings on Forms 10-K and 10-Q, or in information disclosed in public conference calls, the date and time of which are released beforehand. We undertake no obligation, and do not intend, to update these forward-looking statements, to review or confirm analysts' expectations, or to provide interim reports or updates on the progress of the current quarter.

About Illumina

Illumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as a global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical, and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture, and other emerging segments. To learn more, visit illumina.com and connect with us on X, Facebook, LinkedIn, Instagram, TikTok, and YouTube.

Contacts
Investors:
Brian Blanchett
IR@illumina.com

Media:
Christine Douglass
PR@illumina.com

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SOURCE Illumina, Inc.

FAQ

What is Illumina's PromoterAI and how does it work?

PromoterAI is an AI algorithm that uses deep learning neural networks to identify pathogenic regulatory genetic variants in noncoding promoter regions of the human genome, helping to diagnose rare diseases by analyzing areas that comprise 98% of the genome but were previously difficult to interpret.

How much can PromoterAI improve rare disease diagnosis rates?

When combined with Illumina's other AI tools (PrimateAI-3D and SpliceAI), PromoterAI can effectively double the diagnostic yield compared to using protein-truncating variants alone. The technology discovered regulatory variants that contribute up to 6% of genetic causes of rare diseases.

How can researchers access Illumina's PromoterAI technology?

PromoterAI is accessible through Illumina Connected Software and DRAGEN secondary analysis. Precomputed PromoterAI scores for human promoter single-nucleotide variants are freely available for academic and noncommercial research use.

What is the current success rate of rare disease diagnosis using traditional methods?

Currently, only about 30% of rare disease patients receive an accurate diagnosis from exome sequencing, highlighting the need for advanced technologies like PromoterAI to improve diagnosis rates.

What other AI tools has Illumina developed for genetic analysis?

Illumina has developed SpliceAI (2019) for interpreting noncoding cryptic splice mutations and PrimateAI-3D (2023) for predicting pathogenicity of protein-coding variants based on evolutionary conservation and protein structure.