Best practices and pitfalls in using hmmix for reference-free detection of introgressed sequences

Human Population Genetics and Genomics 2025;5(4):0007 | https://doi.org/10.47248/hpgg2505040007

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Best practices and pitfalls in using hmmix for reference-free detection of introgressed sequences

Moisès Coll Macià ¹ , Laurits Skov ²

1. Bioinformatics Research Centre, Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark
2. Section for Molecular ecology and evolution, Globe Institute, University of Copenhagen, Copenhagen, Denmark

Correspondence: Moisès Coll Macià; Laurits Skov

Academic Editor(s): Joshua Akey, Carina Schlebusch, Torsten Günther

Received: Aug 19, 2025 | Accepted: Nov 6, 2025 | Published: Nov 18, 2025

This article belongs to the Special Issue Population Genetics Methods and Software

Cite this article: Coll Macià M, Skov L. Best practices and pitfalls in using hmmix for reference-free detection of introgressed sequences. Hum Popul Genet Genom. 2025;5(4):0007. https://doi.org/10.47248/hpgg2505040007

Abstract

Archaic introgression from Neanderthals and Denisovans has contributed to the genomes of present-day humans, impacting traits such as our immune system. Most methods for detecting archaic ancestry rely on sequenced archaic reference genomes, which limits the detection of ancestry from unsampled or highly diverged archaic populations. Here, we discuss hmmix, a hidden Markov model–based method that infers introgressed genomic segments without requiring archaic reference data, but assumes the availability of an introgression-free outgroup population. We give a brief overview of hmmix; how it works, how to run it and which precomputed resources are available. We also discuss its imitations and recommendations on when and when not to use it and how to run it on species other than humans.

Keywords

hmmix, archaic introgression, Neanderthals, Denisovans, admixture, human history, population genetics

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