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Leveraging FracMinHash Containment for Genomic d N / d S
Judith S Rodriguez1, Mahmudur Rahman Hera2, David Koslicki1,2,3,4
1Huck Institutes of the Life Sciences, The Pennsylvania State University.
Biorxiv : the Preprint Server for Biology
|November 26, 2025
Summary
This study introduces FracMinHash dN/dS, an alignment-free method for estimating evolutionary pressures across genomes. It offers a scalable and accurate alternative to traditional methods, enabling rapid analysis of large genomic datasets.
Area of Science:
- Genomics
- Evolutionary Biology
- Bioinformatics
Background:
- Genomic data is rapidly increasing, necessitating efficient analysis tools.
- Estimating evolutionary pressures using the dN/dS ratio is crucial for understanding adaptation.
- Traditional alignment-based dN/dS methods are computationally intensive and not scalable for large datasets.
Purpose of the Study:
- To develop a novel, alignment-free method for estimating the dN/dS ratio at the genomic level.
- To leverage FracMinHash containment for rapid and scalable evolutionary analyses.
- To compare the accuracy and scalability of the new method against traditional approaches.
Main Methods:
- Utilized FracMinHash containment, a fast similarity measure, to estimate dN/dS ratios.
- Applied the method to simulated and real-world genomic datasets, including large-scale comparisons of bacterial and archaeal genomes.
- Validated the approach by comparing results with conventional alignment-based dN/dS estimations.
Main Results:
- FracMinHash dN/dS provides accurate and scalable genomic-level estimations of evolutionary pressures.
- The method enabled pairwise dN/dS estimations for over 85,000 genomes in under 5 hours.
- Identified a novel metabolic island between specific archaeal and bacterial species, demonstrating the method's utility in discovering biological insights.
Conclusions:
- FracMinHash dN/dS is a powerful, alignment-free tool for large-scale evolutionary genomic analyses.
- The method is comparable in accuracy to traditional approaches but significantly more scalable.
- Facilitates rapid evolutionary inference and functional interpretation across diverse taxa and complex datasets.

