bioRxiv Science⌕ Search

bioRxiv · 10.64898/2026.04.05.714076

Graph transformer for ancient ancestry inference

Abstract

Local ancestry inference classifies segments of DNA in admixed individuals by their originating population. However, as the date of admixture becomes older, these segments become shorter and determining their ancestry becomes increasingly difficult. This limits many existing segment-based methods to relatively recent historical admixture events and more highly diverged populations. The rapidly expanding availability of ancient DNA offers a promising opportunity to use these ancient samples as references for local ancestry inference. A recent approach integrates ancient samples into the ancestral recombination graph (ARG) for local ancestry inference. Here, we introduce recent advances in deep learning for graphs into this ARG framework to create ARGMix, a graph transformer that infers local ancestry using the coalescent trees of the inferred ARG. Our approach employs ancient samples as references in the marginal trees to predict local ancestry. We train ARGMix on data reflecting the well-understood ancient European demography and demonstrate improved accuracy and robustness even under demographic misspecification. We then apply ARGMix to an ARG of ancient and present-day European samples for ancestry-specific analyses, finding evidence of continuity between Otzi the Iceman and present-day individuals from nearby regions.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shanks, C., Bonet, D., Comajoan Cara, M., Ioannidis, A. G.. 2026-04-07. Graph transformer for ancient ancestry inference. https://doi.org/10.64898/2026.04.05.714076

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Integrated exome-transcriptome analysis of a schizophrenia case with an exceptionally low polygenic risk score

Schizophrenia liability reflects both common polygenic variation and rarer variants of larger effect. We investigated a post-mortem schizophrenia case (SZ07) with a schizophrenia polygenic risk score below the first percentile among ancestry-matched cases, asking whether individual-level genomic and transcriptomic analyses could help identify potentially novel schizophrenia-relevant variants. We used exome analysis with multiple variant-prediction tools to generate a panel of variants and corresponding candidate genes potentially implicated in the pathological process in SZ07. The prioritised variants were then assessed using RNA sequencing of three cortical regions. Of these, only an IZUMO4 splice-acceptor variant showed direct RNA-level support. Beyond variant-specific analyses, we characterised broader transcriptomic abnormalities in the SZ07 brain. Pathway analysis of gene-level expression deviations implicated innate immune processes, calcium signalling, synaptic biology, and axon remodelling. Notably, compared with conventional single-sample biological pathway analysis, the analysis we used showed only a weak association with neuronal specificity, suggesting their reduced sensitivity to the main axis of variation related to cellular composition in bulk brain tissue gene expression data. Although the candidate genes showed no significant pathway-level convergence, the broader transcriptomic profile revealed coherent biological alterations largely compatible with the documented history of cerebrovascular disease in SZ07. These results demonstrate how the integration of exome and transcriptome data at the individual level enables the formulation and constraint of hypotheses regarding patient-specific genetic features and their molecular consequences, while highlighting important limitations related to tissue composition, comorbidity, and the choice of reference cohort.

genetics↗

A genetic screen to identify host factors required for commensal bacterial adherence to the gut epithelia

Bacterial adherence to gut epithelial cells likely involves host genetic components. We isolated a gut commensal bacterium, Lelliottia jeotgali, that can robustly colonize C. elegans through attachment to intestinal epithelial cells. Here, we developed a novel screen in C. elegans to identify host genes required for microbiome bacterial colonization. Using transgenic L. jeotgali strain expressing tdTomato, we conducted forward genetic screens in C. elegans to select for mutants that completely lost colonization. We identified multiple allelic mutations in five different C. elegans genes, termed knockout of Lelliottia adherence (kola) mutants, with a near complete loss of adherence. Each of kola-1-5 is uncharacterized and predicted to encode for a secreted or membrane-bound protein. We also identified gly-5, a GalNAc transferase that initiates O-linked glycosylation. Overall, we describe the first C. elegans screen to identify host factors that control microbiome bacterial colonization in the gut.

genetics↗

Male-specific genome sequences for non-invasive sex identification in Nishikigoi (Cyprinus carpio)

Nishikigoi, ornamental cultivars of the common carp (Cyprinus carpio), are economically valuable aquaculture teleosts in which mature females command significantly higher market prices due to superior body conformation and coloration. Consequently, early and non-invasive sex identification is highly desirable for commercial breeding. Although sex determination in common carp follows an XX/XY system, sex-chromosome-specific markers and field-applicable diagnostic methods for Nishikigoi have remained limited. In this study, we conducted sequence-based bulked segregant analysis using whole-genome shotgun sequencing of female and male pools in Kohaku, a representative Nishikigoi lineage. We identified male-specific candidate contigs and successfully developed PCR-based male-specific markers. Validation across multiple Nishikigoi varieties and wild common carp demonstrated that primary primer pairs achieved high diagnostic accuracy. Comparative genomic analysis revealed that these candidate contigs mapped to the genomic region on chromosome 25B containing the male-determining gene Pangu, with the primary marker located in immediate physical proximity to the gene. To enable field diagnostics, we combined non-invasive epidermal mucus DNA extraction, loop-mediated isothermal amplification (LAMP), and chromatography-printed array strip (C-PAS) technology, establishing a rapid on-site detection workflow. Overall, this study provides highly reliable PCR markers associated with the sex-determination locus and establishes a non-invasive, field-applicable diagnostic platform to streamline commercial Nishikigoi breeding and sex-selected stock management.

genetics↗