Biology subjects

Vyazov, L. A.

Publications and source records attributed to Vyazov, L. A..

3 recordsLinked to original sources

bioRxiv2026

Sparse sampling and rare-variant depletion distort PCA visualizations of population structure: recovery with objective-guided manifold learning

Principal component analysis (PCA) is routinely used to visualize population structure, yet how sparse sampling and rare-variant depletion affect low-dimensional plots remains poorly understood. Using spatial simulations, we show that these factors interact to distort visualization of genetic landscapes, producing triangular and three-ray patterns, artificial outliers and misleading clines. We develop an objective-guided manifold-learning framework that searches across genotype normalization, PCA representation and dimensionality, distance metrics, and UMAP, densMAP and PHATE parameters. High-dimensional classic PC scores consistently outperform the eigenvectors used in population genetics, but other optimal parameters and ranking objectives depend on data quality, sampling and SNP ascertainment. Across six human and animal datasets, optimized embeddings recover fine-scale structure obscured by PCA and supported by independent genetic evidence. In ancient Eurasia, optimized PHATE resolves Slavic-associated structure corroborated by haplotype-sharing communities, qpAdm, and Y-chromosome lineages. These results call for caution in interpreting PCA plots and establish optimized manifold learning as a hypothesis-generating approach.

genetics↗

bioRxiv2023

False discovery rates of qpAdm-based screens for genetic admixture

qpAdm is a statistical tool that is often used for testing large sets of alternative admixture models for a target population. Despite its popularity, qpAdm remains untested on two-dimensional stepping-stone landscapes and in situations with low pre-study odds (low ratio of true to false models). We tested high-throughput qpAdm protocols with typical properties such as number of source combinations per target, model complexity, model feasibility criteria, etc. Those protocols were applied to admixture-graph-shaped and stepping-stone simulated histories sampled randomly or systematically. We demonstrate that false discovery rates of high-throughput qpAdm protocols exceed 50% for many parameter combinations since: 1) pre-study odds are low and fall rapidly with increasing model complexity; 2) complex migration networks violate the assumptions of the method, hence there is poor correlation between qpAdm p-values and model optimality, contributing to low but non-zero false positive rate and low power; 3) although admixture fraction estimates between 0 and 1 are largely restricted to symmetric configurations of sources around a target, a small fraction of asymmetric highly non-optimal models have estimates in the same interval, contributing to the false positive rate. We also re-interpret large sets of qpAdm models from two studies in terms of source-target distance and symmetry and suggest improvements to qpAdm protocols: 1) temporal stratification of targets and proxy sources in the case of admixture-graph-shaped histories; 2) focused exploration of few models for increasing pre-study odds; dense landscape sampling for increasing power and stringent conditions on estimated admixture fractions for decreasing the false positive rate. Article SummaryProliferation in the archaeogenetic literature of protocols for detection of admixed groups based a so-called qpAdm algorithm became disconnected from performance testing: the only extensive study of qpAdm on simulated data showed that it performs well under an unrealistically simple demographic scenario. We found that false discoveries of gene flows by qpAdm on a collection of random admixture-graph-shaped histories and on complex stepping-stone landscapes are very common and provide guidelines for design of qpAdm protocols in archaeogenetic studies.

genetics↗

bioRxiv2020

The genomic formation of First American ancestors in East and Northeast Asia

Upward Sun River 1, an individual from a unique burial of the Denali tradition in Alaska (11500 calBP), is considered a type representative of Ancient Beringians who split from other First Americans 22000-18000 calBP in Beringia. Using a new admixture graph model-comparison approach resistant to overfitting, we show that Ancient Beringians do not form the deepest American lineage, but instead harbor ancestry from a lineage more closely related to northern North Americans than to southern North Americans. Ancient Beringians also harbor substantial admixture from a lineage that did not contribute to other Native Americans: Amur River Basin populations represented by a newly reported site in northeastern China. Relying on these results, we propose a new model for the genomic formation of First American ancestors in Asia. One Sentence SummaryAncient Beringians do not form the deepest American lineage, but harbor admixture from Amur River Basin populations.

genetics↗