CNEwrap: a scalable toolkit with a novel algorithm for large-scale genome-wide accelerated conserved non-coding...

Conserved non-coding elements (CNEs) are fundamental components of gene regulatory networks in eukaryotes, yet their reliable identification across large-scale genomes and systematic evaluation of their genetic variation remains technically challenging, limiting comprehensive insights into their functional roles. To address these challenges, CNEwrap (https://github.com/YanCCscu/CNEwrap) was developed as a streamlined and modular bioinformatics toolkit that integrates subprograms capable of performing diverse tasks ranging from whole-genome alignment to CNE scanning and accelerated evolution analysis. Designed for high-throughput, multi-species applications, CNEwrap enables efficient and accurate discovery of genome-wide CNEs and comparative analysis of their variation across diverse taxa. Specifically, we developed a novel algorithm, "EvoAcc," designed for assessing accelerated evolution of specific species in different scenarios from CNE alignments. The EvoAcc algorithm integrates nucleotide variation frequencies and phylogenetic relationships to reconcile global conservation with clade-specific divergence, outperforming PhyloAcc, PhyloP, and ForwardGenomics in simulated datasets, particularly in scenarios involving two or three accelerated lineages. In validation analyses of functional genomic fragments across mammal species, EvoAcc performed comparably to existing algorithms in detecting human-specific accelerated segments while exhibiting superior sensitivity for InDel mutations and recovering specific signals missed by other algorithms. Case studies further confirm that CNEwrap is broadly applicable within diverse evolutionary lineages. Collectively, the CNEwrap pipeline establishes a scalable and integrative framework for uncovering CNEs and their evolutionary dynamics, while the incorporated EvoAcc algorithm complements existing methodologies, deepening insights into conserved regulatory architectures across eukaryotic evolution.