EXCON: a scalable, reproducible Nextflow pipeline for CAFE-based gene EXpansion and CONtraction analysis

The article introduces EXCON, a Nextflow pipeline designed for gene family expansion and contraction analysis. Gene family analysis is a crucial method in evolutionary comparative genomics to pinpoint lineage-specific evolutionary pressures affecting gene copy or family numbers. CAFE is a popular tool for measuring changes in gene family size, but it demands a high level of bioinformatics expertise, manual parameter tuning, and preprocessing.

EXCON is an automated, community-developed pipeline built using the Eco-Flow framework. It integrates various steps including NCBI genome download, annotation quality and format pre-processing, orthologous gene family identification using Orthofinder, ultrametric tree formatting, birth-death modelling with CAFE, and GO enrichment analysis using eggNOG-mapper and TopGO.

EXCON can handle genome assemblies and annotations, and it supports local, HPC, and cloud-based computing environments. It requires minimal user configuration and auto-selects appropriate CAFE lambda and error models, separating high variance orthogroups for separate treatment.

The pipeline was applied to a dataset of 24 primate species spanning Catarrhini, Platyrrhini, and Strepsirrhini. It identified 358 rapidly evolving gene families, including a DUX (double homeobox) gene that showed repeated, independent copy-number turnover across multiple lineages. This finding is consistent with the known instability of the D4Z4 macrosatellite repeat where the DUX gene resides. EXCON is freely available on GitHub at https://github.com/Eco-Flow/excon.