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Next-generation sequencing (NGS) is becoming a routine approach in most domains of the life sciences. To ensure reproducibility of results, there is a crucial need to improve the automation of NGS data processing and enable forthcoming studies relying on big datasets. Although user-friendly interfaces now exist, there remains a strong need for accessible solutions that allow experimental biologists to analyze and explore their results in an autonomous and flexible way. The protocols here describe a modular system that enable a user to compose and fine-tune workflows based on SnakeChunks, a library of rules for the Snakemake workflow engine. They are illustrated using a study combining ChIP-seq and RNA-seq to identify target genes of the global transcription factor FNR in Escherichia coli, which has the advantage that results can be compared with the most up-to-date collection of existing knowledge about transcriptional regulation in this model organism, extracted from the RegulonDB database. © 2019 by John Wiley & Sons, Inc., (© 2019 John Wiley & Sons, Inc.)