Solving the Unresolved: A New Era of Insights in Rare Disease Genomics with GenomeArc Horizon

Mississauga, Ontario

Rare disease genomics has made remarkable strides in the past decade, offering hope to countless families searching for answers. Yet, despite these advances, a significant proportion of complex rare disease cases remain unresolved. Current diagnostic tools or algorithms, primarily based on the American College of Medical Genetics and Genomics (ACMG) criteria, are equipped with poor databases, or algorithmic capabilities to uncover the underlying pathogenicity of variants, leaving patients and clinicians in a diagnostic limbo.

At GenomeArc, we recognize that rare disease diagnosis requires more than traditional methods. This is why we’re proud to announce the launch of Solving the Unresolved, a groundbreaking global initiative designed to empower scientists and laboratories to tackle their toughest cases using our state-of-the-art multimodal OMICs platform, GenomeArc Horizon^TM.

The Challenges in Rare Disease Genomics

The genetic landscape of rare diseases is extraordinarily complex. While ACMG guidelines provide a robust framework for variant interpretation, they can fall short when addressing variants of uncertain significance (VUS) or cases with limited insight on pathogenicity. Many unresolved cases stem from:

• Insufficient Data on Variants: Small, isolated datasets lack the depth to accurately classify many rare variants.
• Lack of Multi-OMICs Integration: Genomic data alone often misses the broader context of disease, which can be illuminated by integrating genomic, transcriptomics and proteomics data.
• Complexity of Rare Disease Pathogenesis: Some cases require a deeper understanding of the gene-phenotype, gene-environment interactions, and pathway-level effects.



GenomeArc Horizon^TM: Powering the “Solving the Unresolved” Initiative

The GenomeArc Horizon^TM multimodal platform is purpose-built to address these challenges and redefine the diagnostic potential in rare disease genomics. Here’s how:

• Enable ACMG-Guided Diagnosis with Enhanced Insights: Our advanced algorithms leverage ACMG criteria while integrating supplementary evidence from global clinical genomic resources to reclassify and resolve VUS. GenomeArc Horizon^TM has a proprietary database of over 1 million rare variants from numerous complex rare genetic disorders.
• Multimodal OMICs Integration: By combining genomics, transcriptomics, proteomics, and metabolomics, GenomeArc Horizon^TM provides a comprehensive molecular view, uncovering insights that would remain hidden in single-dimensional analyses. GenomeArc HorizonTM platform integrates multimodal proteomics, and sign cell transcriptomics datasets across different tissues to link with variants/genes.
• Horizon Intelligence: Our AI-powered engine not only streamlines data analysis but also identifies novel patterns and connections across datasets, enhancing diagnostic yield. Our in-built LLM trained with custom databases allows us to infer rich insights on genes and variants.
• Global Rare Disease Genomic Resources: By pooling data from diverse clinical and research collaborations, we bring a richer context to rare variant interpretation.

Unlocking the True Potential of Rare Disease Diagnosis

The Solving the Unresolved initiative invites scientists and laboratories worldwide to experience the transformative power of the GenomeArc Horizon^TM platform. Whether it’s reanalyzing previously unresolved cases or tackling new complex ones, this initiative offers access to:

• Access to GenomeArc Horizon^TM platform.
• Expertise from GenomeArc’s world-class genomic research team.
• A collaborative framework for sharing scientific knowledge and improving outcomes

Through this project, by partnering with laboratories and clinicians around the globe, we aim to assess the full potential of GenomeArc Horizon^TM in solving the unsolved cases.

To join the Solving the Unresolved initiative, please email project@genomearc.com