NEW YORK – Researchers in Ireland have commenced a five-year project to introduce whole-genome sequencing into pediatric cancer care.
The aims of the Molecular and Genomic Interrogation of Childhood Cancer-Ireland (MAGIC-I) project are manifold and include gaining better insight into disease development as well as testing out personalized treatment approaches. All children and adolescents with cancer in Ireland, including those who relapse following treatment, will be offered enrollment in the effort.
Owen Smith, a professor of child, adolescent, and young adult oncology at Trinity College Dublin and a professor at Systems Biology Ireland (SBI) at University College Dublin, is the principal investigator for MAGIC-I. According to him, about 200 children and young adolescents aged 0 to 16 each year are diagnosed with cancer in Ireland, which has a population of about 5.3 million. Those patients will all be offered to participate in MAGIC-I, as will the roughly 20 to 30 patients per year who relapse.
Walter Kolch, director of the SBI and another MAGIC-I investigator, said the total cost of the study will be around €2.8 million ($3.2 million). Funding is provided by an anonymous philanthropic donation to UCD to support the combination of clinical activities at Children's Health Ireland hospitals with computational modeling and data science expertise at the SBI. Precision Oncology Ireland, a consortium of Irish universities, charities, and companies, is also supporting MAGIC-I.
The new project also has some commercial partners, including Illumina, which Kolch said will be providing the researchers with its Dragen software for next-generation sequencing data analysis as well as sequencing reagents free of charge. Genseq, an Irish genomic services company based in Dublin's Cherrywood Business Park, will perform the sequencing for MAGIC-I at a discounted price.
Kolch underscored that the industry partners "do not have any rights to the data being produced, and there will be no commercial use of the data at all."
At the SBI, Kolch has been involved in a project for a decade that aims to create digital twins to guide patient treatment selection through trialing different outcomes with the help of AI and computational modeling. In particular, such digital twins could be used to anticipate patient response to therapies and the development of drug resistance.
Kolch said a novelty of the MAGIC-I project will be the construction of a digital twin for every participating patient. By using these in silico models or avatars, the investigators hope to predict how well patients will respond to chemotherapy and whether the therapy will cause severe side effects.
"As the research and clinical studies run side by side, we will be able to monitor the performance of the digital twin models in real time," he said, adding that such tools could be used in the future to design tailored therapies for each patient, maximizing treatment efficacy while minimizing side effects.
Smith said the use of genome sequencing data will provide "critical advances" here, as it will enable the researchers to understand disease development as well as patient response to therapy and why some relapse later than others. He defined success as the "seamless integration of genome sequencing into the standard care pathway" and use of the information as part of the clinical diagnostic and treatment pathways.
"The success of the research arm will be assessed by the performance of the digital twin models, whether they predict correctly the response of a patient to chemotherapy and the side effects," Smith remarked. "This is possible because the simulations will be done in parallel to the treatment, allowing us in real time to compare the real-world observations with the model simulations."
The MAGIC-I project coincides with numerous genomics-related developments in Ireland. In February 2023, Health Service Executive, the country's publicly funded healthcare system, published its National Strategy for Accelerating Genetic and Genomic Medicine in Ireland. Colm Henry, chief clinical officer of the HSE, said in a statement this week that the launch of MAGIC-I is a "great example for the vision of introducing genome sequencing and accompanying research into clinical care" that was laid out in that strategy.
Kolch said that the HSE is currently not supporting the study, but SBI and the MAGIC-I team will "work closely with the HSE to implement genome sequencing as standard care for childhood cancers in the future."
Also in 2023, Irish researchers embarked on Genomic Data Infrastructure (GDI) Ireland, which aims to create a secure data infrastructure for Irish genomic and clinical data. Partly funded by the EU, this hub is being established to support the aims of the European 1+ Million Genomes initiative.
Kolch said that MAGIC-I will work closely with GDI Ireland and the 1+ Million Genomes initiative in terms of exchanging knowledge and best practices. MAGIC-I will also ask parents and patients for consent in order to make their genome data available via the European Genome Phenome Archive.