The RE(ACT) Congress & IRDiRC Conference 2025, an international platform for knowledge sharing on rare and orphan diseases, has been a catalyst for scientific collaboration and advancement since its inception in 2012. Co-organized by BLACKSWAN Foundation, IRDiRC (International Rare Diseases Research Consortium), and ERDERA (European Rare Diseases Research Alliance), the congress brings together researchers, clinicians, and stakeholders from around the world to discuss the latest developments in rare disease research. This year, ERDERA played a key role in the event, featuring a series of insightful talks, including one by Vicente Yepez from the Technical University of Munich, who shared his expertise on data and diagnosis within the context of ERDERA.
The role of RNA sequencing in rare disease diagnosis
Yepez emphasized the importance of RNA sequencing as a complementary tool to DNA analysis. He explained, “In rare diseases, the first thing that a patient does after being clinically diagnosed is a DNA test. In some cases, the DNA test is conclusive, but in others, it’s inconclusive. RNA can be quite useful because it can be quantified, unlike DNA.” This quantification allows researchers to measure the expression levels of up to 12,000 genes, providing a comprehensive overview of potential genetic anomalies.
One of the key advantages of RNA sequencing is its ability to identify outliers in gene expression. Yepez noted, “We quantify how much RNA molecules are present for up to 12,000 genes. We define these ranges and then we tell, ‘Oh look, this gene in this person is outside the range.'” This process helps pinpoint the exact genetic mutations that may be causing the disease, offering a more precise diagnosis.
Challenges and solutions in implementing RNA sequencing
Despite its benefits, RNA sequencing faces several obstacles in clinical settings. Yepez highlighted cost as a significant barrier, estimating it to be around €1,000 per case. He stated, “It includes experimental costs, analysis costs, and storage costs. Each file is around 10 gigabytes.” Additionally, the need for specialized equipment and expertise further complicates its widespread adoption. Another challenge is the limitation of tissue samples. Yepez explained, “60% of all genes are working in your blood; the rest are working in your brain, liver, heart, and so on. We are completely bound to the blood and the cost.” This restriction makes it difficult to analyse genes that are active in other parts of the body, particularly those linked to neurological conditions.
ERDERA’s role in promoting RNA sequencing
ERDERA, a European program supported by the European Union and participating countries, aims to address these challenges by fostering innovation and collaboration in rare disease research. According to Yepez, “Having a huge network with lots of samples coming from all different parts, lots of collaborators, and people that give you feedback allows me as a bioinformatician to build a good model to be able to properly model these ranges.” This network is crucial for developing new methods and statistical tools to enhance RNA sequencing analysis.
One of ERDERA’s missions is to unify knowledge, resources, and expertise to support rare disease research projects across Europe. By boosting clinical research and enabling patients to contribute to high-quality evidence generation, ERDERA is paving the way for more effective diagnosis and treatment options.
The impact of the RE(ACT) Congress & IRDiRC Conference
The RE(ACT) Congress & IRDiRC Conference serves as a platform for knowledge sharing and collaboration among researchers, clinicians, and stakeholders in the field of rare diseases. Yepez expressed his enthusiasm for the event, stating, “It provides an opportunity to collaborate and talk. It’s not just European; I saw people from South Africa, Australia, the US, and even China.” This global perspective is essential for understanding the diverse challenges and opportunities in rare disease research.
Looking ahead, Yepez is optimistic about the future of RNA sequencing and its integration into routine clinical practice. He envisions a system where genetic data can be easily shared and analysed across borders, facilitating faster and more accurate diagnoses. “If somebody sequences a sample in Ecuador, they can upload the file to me in Germany in one day. The input is the same that I will get from Belgium or Sweden or Canada.”
Conclusion
The insights shared by Vicente Yepez at the RE(ACT) Congress & IRDiRC Conference underscore the critical role of RNA sequencing in advancing rare disease diagnosis. Through collaborative efforts like ERDERA, researchers are making significant strides in overcoming the challenges associated with RNA sequencing and improving the lives of patients with rare diseases. As Yepez aptly put it, “Our goals align with ERDERA’s goals. It makes sense to present and work together to make tools better and more accessible.”
