The concordance project

Microbiome analysis is essential for understanding microbial interactions and their impact on human health. Advances in next-generation sequencing (NGS) have led to two widely used methods: 16S rRNA gene sequencing and metagenomic shotgun sequencing. While 16S sequencing enables broad taxonomic classification and phylogenetic analysis, shotgun sequencing provides higher taxonomic resolution and functional insights but at a higher cost. However, their comparative efficacy remains uncertain, complicating study design. To address this, we introduce CoMPaSS (Concordance of Microbiome Sequencing Platforms and Study Initiation Strategy), a computational pipeline for navigating microbiome study design. CoMPaSS systematically evaluates sequencing concordance across multiple levels, from community diversity to taxonomic composition, and provides power analysis, sample size estimation, and cost assessment to support study planning. Through extensive simulations and real-world microbiome studies, we found moderate concordance at broader taxonomic levels but significant discrepancies at finer levels and for rare taxa, emphasizing the impact of sequencing method selection on study outcomes. By integrating statistical and computational insights, CoMPaSS helps researchers optimize study design based on scientific and budgetary constraint.