On December 4th 2025, at the 36th International Symposium on ALS/MND in San Diego, Jan Veldink presented updates on Data Freeze 3 (DF3), recent advances in in-house WGS capacity, plans for Data Freeze 4 (DF4) and updates were presented from a number of working groups by Johnathan Cooper-Knock, Kevin Kenna, Alfredo Iacoangeli and Ross Byrne.
On December 4th 2025, at the 36th International Symposium on ALS/MND in San Diego, Jan Veldink presented updates on Data Freeze 3 (DF3), recent advances in in-house WGS capacity, plans for Data Freeze 4 (DF4) and updates were presented from a number of working groups by Johnathan Cooper-Knock, Kevin Kenna, Alfredo Iacoangeli and Ross Byrne.
DF3 included comprehensive sample- and variant-level quality control across all participating cohorts. WGS was performed using the NovaSeq X Plus platform with PCR-free library preparation, achieving a median depth of 30× with ≥80% of bases reaching the target coverage. Data visualization and variant exploration are supported through ongoing development of the new to be released Project MinE browser.
Following QC, DF3 comprised 11,888 high-quality genomes, including 9,059 ALS cases and 2,571 controls, representing substantial growth relative to DF2. Variant QC was nearing completion at the time of reporting. Establishment of fully operational in-house WGS capacity significantly reduced sequencing costs (approximately 300 EUR per sample) and enabled rapid, scalable production of high-quality genomic data, contingent on appropriate informed consent and maintenance of ~3–4:1 case-to-control ratios. Enhancements to the Project MinE browser provide richer annotations, improved usability, and expanded access to harmonized datasets.
DF4 will be processed on the DNA Nexus (AWS) platform, chosen for its ISO27001-certified environment, with all legal and data-governance required documents in place (DPIA, DPA, DMP, MSA, SCC), and seamless sharing of harmonized datasets, including those aligned with the UK Biobank. DNA Nexus will facilitate joint access, scalable computational workflows, and integration of multimodal data (e.g., MRI, proteomics, NfL). High-throughput computation will continue to utilize SURF infrastructure.
Project MinE has reached a major inflection point with the expansion of high-quality genomic data, the launch of a cost-efficient in-house WGS pipeline, and the planned migration to a secure, cloud-based environment for DF4. These developments significantly strengthen the consortium’s capacity to detect novel ALS-associated genetic variation and accelerate the discovery of disease mechanisms.