Genes, Language, Immunity: Insights from local ancestry inference leveraging ancient DNA and biobank sources, a seminar with practical workshop

Local ancestry inference (LAI) can be used to map disease loci, investigate relationships between modern populations, improve association studies, and study demographic histories.

We will begin with a seminar-style session designed for interdisciplinary researchers, where we explore the insights that LAI can offer. This will give important insights to medicine in the form of human immune disease, as well as interdisciplinary insights in linguistics and culture as part of the OCSEAN (Oceanic and Southeast Asian Navigators) project. After a break we will follow a practical workshop aimed to give an overview of how to work with LAI, focusing on recent scalable algorithms designed for identifying fine-scale population structure under different use cases spanning biobank scale modern datasets to ancient DNA. Participants can attend the first session only.

During the opening session, we will examine how LAI has been crucial for inferring the origins of multiple sclerosis and other immune‑related diseases by integrating evidence from both ancient and modern DNA. This leads to the isolation of specific genes and tells a story of very recent - perhaps ongoing - selection on human populations. We’ll also compare local ancestry relationships to linguistic relationships and discuss what data might be needed to test concrete hypotheses about gene-language cultural co-evolution.

Despite these clear benefits, performing LAI accurately and efficiently has remained challenging. In the second part we’ll discuss how to use the most up-to-date LAI software packages, each with its own distinctive features, which allow handling large biobank-scale datasets. Newly developed methods are capable of processing hundreds of thousands to millions of samples—sizes typical of the most demanding modern biobanks and association studies. Conversely, researchers interested in population history may be restricted to hundreds of individuals, and therefore focus on tools that carefully retain genetic relationships. Both sets of tools are increasingly accessible.

Outline of the Seminar (part 1):

1. Introduction to LAI
2. Use in Population History
3. Identifying genes under selection

4. Towards gene-language co-evolution

Outline of the Workshop (part 2):

5. A brief overview of the concept and currently available software
6. Introduction to SparsePainter and PBWTpaint
7. Practical usage

• Building the reference panel

• Imputation & Phasing

• Applying SparsePainter and PBWTpaint to a concrete use case to detect selection on disease-associated loci