- With the aim of improving the consistency of analyses of next-generation sequencing data across centres, CNAG has developed CBIcall, a flexible framework that enables standardised workflows to run from raw sequencing data to analysis-ready VCF files.

 

- The new system, developed by the Biomedical Genomics Group at CNAG, has been tested in the EU HEREDITARY Project, where it processed 1,102 samples using both whole-exome sequencing (WES) and mitochondrial DNA (mtDNA) pipelines.

 

 

October 6, 2026. Following the publication of the first human genome sequence 25 years ago, genomic research has progressed at an unprecedented pace, driven in part by the emergence of next-generation sequencing (NGS). Since then, generating DNA and RNA sequencing data has become faster and more affordable. At the same time, bioinformatics tools and software have continued to evolve to keep pace with the growing volume and complexity of genomic data. For many years, however, individual institutions processed these data using a wide range of tools and approaches, often adapted to their own computing environments and local policies. As collaborative research projects expanded across Europe, federated analysis models became increasingly common. However, differences in software environments, computing policies and resources continue to affect reproducibility and lead to inconsistent results.

 
In this context, researchers from the Biomedical Genomics Group at CNAG have developed CBIcall as part of the EU Horizon Europe HEREDITARY Project, which aims to improve disease detection, treatment and medical knowledge through an integrated framework that combines diverse health data, including genetic information, while ensuring compliance with privacy requirements. CBIcall builds on CNAG's extensive experience in large-scale collaborative sequencing projects, including initiatives such as the Genome of Europe, and the the 1+ Million Genomes initiative. Rather than introducing a new workflow engine, CBIcall provides a configuration-driven framework for validating, executing and auditing analyses, while orchestrating existing workflows through Bash, Cromwell, Nextflow and Snakemake. 
 
"For the HEREDITARY project, we realised 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.”, says Dr Manuel Rueda, co-first author of the study and bioinformatician at CNAG, who designed CBIcall together with Dr Dietmar Fernandez-Orth and Dr Ivo Gut, Director of CNAG.
 
A key strength of CBIcall is that it enables variant-calling workflows to be carried out consistently and reproducibly across different institutional computing environments, including high-performance computing (HPC) clusters commonly used by large-scale sequencing centres. The framework takes analyses from raw FASTQ files, which store the sequencing reads and their quality information, through to analysis-ready VCFs, which list the genetic variants identified in the data. It includes standardised pipelines for germline whole-exome sequencing (WES), whole-genome sequencing (WGS) and mitochondrial DNA analysis..
 
The performance of CBIcall was assessed using public benchmark datasets, while its reproducibility was tested across four different setups. The framework was then put into practice within the EU HEREDITARY Project, where it was used to analyse 1,102 samples with WES and mitochondrial DNA pipelines on an institutional HPC system. This real-world application further supports the use of CBIcall for reproducible genomic analyses involving large cohorts. The open source software is distributed with ready-to-run pipelines, and all the installation documentation is now at Github.  This project has received funding from the HEREDITARY Project as part of the European Union’s Horizon Europe research and innovation programme under grant agreement No GA 101137074.
 
 
 
REFERENCE ARTICLE
Manuel Rueda, Dietmar Fernandez-Orth, Ivo G Gut, CBIcall: a configuration-driven framework for variant calling in large sequencing cohorts, Bioinformatics Advances, Volume 6, Issue 1, 2026, vbag232, https://doi.org/10.1093/bioadv/vbag232