This new system enables standardized workflows from raw sequencing data to analysis-ready VCF files. The system was successfully tested within the EU's HEREDITARY Project, where it processed 1,102 samples using both whole-exome sequencing (WES) and mitochondrial DNA (mtDNA) pipelines.
Developed by CNAG's Biomedical Genomics Group, CBIcall addresses the challenges of reproducibility and inconsistent results that arose from the diversity of tools and approaches previously used by institutions. The need for a common framework became evident with the expansion of collaborative research projects across Europe.
The framework builds on CNAG's experience in large-scale sequencing projects, including initiatives like the Genome of Europe and the 1+ Million Genomes initiative. Rather than introducing a new workflow engine, CBIcall provides a configuration-driven system for validating, executing, and auditing analyses, orchestrating existing workflows through Bash, Cromwell, Nextflow, and Snakemake.
“"For the HEREDITARY project, we realized that we needed a way to run variant-calling pipelines consistently across different sites and computing environments, while also being able to audit and compare the results. Many of the pieces of the puzzle were already there, but there was nothing that brought them all together in a single package."
A key strength of CBIcall is its ability to perform variant-calling workflows consistently and reproducibly across different institutional computing environments, including high-performance computing (HPC) clusters common in large-scale sequencing centers. The framework processes data from FASTQ files to VCFs, including standardized pipelines for WES, WGS (whole-genome sequencing), and mitochondrial DNA analysis.
CBIcall's performance has been evaluated with public benchmark datasets, and its reproducibility has been tested across four different setups. Its practical application within the HEREDITARY Project, analyzing 1,102 samples, supports its use for reproducible genomic analyses involving large cohorts. The open-source software is available on Github with installation documentation.
