Search bioRxiv⌕ Search

Biology subjects

Torok, T.

Publications and source records attributed to Torok, T..

11 recordsLinked to original sources

Genomic landscape of the medieval Hungarian elite from the Szekesfehervar royal necropolis

We analyzed 399 shotgun genomes from the Royal Basilica of Szekesfehervar, representing the elite of the Medieval Hungarian Kingdom. Our results reveal that the Carpathian Basin population underwent a marked homogenization during the Middle Ages, driven largely by admixture with eastern immigrant groups, especially the conquering Hungarians, resulting in a genomic landscape distinct from that of the surrounding European populations. The European ancestry component also shifted: the Avar-period Balkan element disappeared, while northern and northwestern European ancestry increased, likely reflecting changing political connections. We identified a previously unrecognized Conquest-period stratum at the site, including two individuals closely related to the Arpad dynasty. No large, continuous kinship networks were detected, indicating a dynamic and continuously renewed elite. At the population level, the strongest affinities were observed with the Conq_Asia_Core group and its ancestor, the Karayakupovo horizon, as well as with medieval populations from neighboring regions (present-day Croatia, Serbia, Slovakia, Poland, and Montenegro), reflecting the diverse sources of the medieval Hungarians.

genetics↗

LARIS enables accurate and efficient ligand and receptor interaction analysis in spatial transcriptomics

Advances in spatially resolved transcriptomics provide unprecedented opportunities to characterise intercellular communication pathways. However, robust and computationally efficient incorporation of spatial information into intercellular communication inference remains challenging. Here, we present LARIS (Ligand And Receptor Interaction analysis in Spatial transcriptomics), an accurate and scalable method that identifies cell type-specific and spatially restricted ligand-receptor (LR) interactions at single-cell or bead resolution. LARIS is compatible with all spatial transcriptomic technologies and quantifies specificity, infers sender-receiver directionality, and detects how differential interactions vary across time and space. To compare LARIS with existing methods, we established a simulation framework to generate ground truth of LR interactions with defined tissue architecture and gene expression patterns. LARIS demonstrates superior performances over other methods in accuracy and scalability. We further applied LARIS to human tonsil and developing mouse cortex spatial transcriptomics datasets collected from various spatial techniques. This uncovered the signalling mechanisms shaping tissue organisation and their changes over time. LARIS reveals cell type-, niche-, and condition-specific signalling and scales to hundreds of thousands of cells in minutes. This provides an efficient and direct method for discovering the molecular interplay between apposed cells across development.

bioinformatics↗

Multi-omic human neural organoid cell atlas of the posterior brain

Patterning of the neural tube establishes midbrain and hindbrain structures that coordinate motor movement, process sensory input, and integrate cognitive functions. Cellular impairment within these structures underlie diverse neurological disorders, and in vitro organoid models promise inroads to understand development, model disease, and assess therapeutics. Here, we use paired single-cell transcriptome and accessible chromatin sequencing to map cell composition and regulatory mechanisms in organoid models of midbrain and hindbrain. We find that existing midbrain organoid protocols generate ventral and dorsal cell types, and cover regions including floor plate, dorsal and ventral midbrain, as well as adjacent hindbrain regions, such as cerebellum. Gene regulatory network (GRN) inference and transcription factor perturbation resolve mechanisms underlying neuronal differentiation. A single-cell multiplexed patterning screen identifies morphogen concentration and combinations that expand existing organoid models, including conditions that generate medulla glycinergic neurons and cerebellum glutamatergic subtypes. Differential abundance of cell states across screen conditions enables differentiation trajectory reconstruction from region-specific progenitors towards diverse neuron types of mid- and hindbrain, which reveals morphogen-regulon regulatory relationships underlying neuronal fate specification. Altogether, we present a single-cell multi-omic atlas and morphogen screen of human neural organoid models of the posterior brain, advancing our understanding of the co-developmental dynamics of regions within the developing human brain.

developmental biology↗

Archaeogenetic analysis revealed East Eurasian paternal origin to the Aba royal family of Hungary

The Aba family played a pivotal role in the early history of Medieval Hungary dominating extensive territories and giving rise to influential figures. We conducted an archaeogenetic examination of remains uncovered at the necropolis in Abasar, the political centre of the Aba clan, to identify Aba family members and shed light on their genetic origins. Utilizing Whole Genome Sequencing (WGS) data from 19 individuals, complemented by radiocarbon measurements, we identified 6 members of the Aba family who shared close kinship relations. Our analysis revealed that 4 males from this family carried identical N1a1a1a1a4[~] haplogroups. Significantly, our phylogenetic investigation traced this royal paternal lineage back to Mongolia, strongly suggesting its migration to the Carpathian Basin with the conquering Hungarians. Genome analysis, incorporating ADMIXTURE, Principal Component Analysis (PCA), and qpAdm, revealed East Eurasian patterns in the studied genomes, consistent with our phylogenetic results. Shared Identity by Descent (IBD) analysis confirmed the family kinship relations and shed light on further external kinship connections. It revealed that members of the Aba family were related to members of prominent Hungarian medieval noble families the Arpads, Bathorys and Corvinus as well as to the first-generation immigrant elite of the Hungarian conquest.

genetics↗

aHISplex: an imputation based method for eye, hair and skin colour prediction from low coverage ancient DNA

The prediction of externally visible traits (eye, hair and skin colours) from DNA can provide valuable information for both contemporary and ancient human populations. The validated HIrisPlex-S method is the primary tool in forensics for phenotyping modern samples. The HIrisPlex-S multiplex PCR assay can handle trace DNA from modern samples, but the analysis of degraded, low coverage ancient DNA (aDNA) presents additional challenges. Genotype imputation has recently proven successful in effectively filling in missing information in aDNA sequences. To assess the feasibility of this approach, we evaluated how key factors, such as genome coverage, minor allele frequency, extent of post mortem damage, and the population origin of the test individual influence the efficiency of imputing HIrisPlex-S markers and predicting phenotypes. We used high coverage sequence data from ancient remains for the evaluation. Our results demonstrate that even with genome coverages as low as 0.1-0.5x, the proposed workflow is capable of predicting phenotypes from degraded ancient (or forensic) WGS data with good accuracy. To aid the archaeogenetics community, we have developed a user-friendly, easily deployable imputation-based framework that includes the new bioinformatics tools and the pre-made reference data sets required for the whole analysis.

genomics↗

Whole genome analysis sheds light on the genetic origin of Huns, Avars and conquering Hungarians

Huns, Avars and conquering Hungarians were Migration Period nomadic groups which arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on historical data each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations has been debated. In this study we have sequenced 9 Hun, 143 Avar and 113 Hungarian conquest period samples, and identified three core populations, representing immigrants from each period, with no recent European ancestry. Our results suggest that this "immigrant core" of both Huns and Avars originated in present day Mongolia, and their origin can be traced back to Xiongnus. On the other hand, the "immigrant core" of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians and descendants of late Xiongnus. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups we identified that the majority of the individuals from each period were local residents, harboring "native European" ancestry.

genetics↗

Maternal lineages from 10-11th century commoner cemeteries of the Carpathian Basin

BackgroundNomadic groups of conquering Hungarians played a predominant role in Hungarian prehistory, but genetic data are available only from the immigrant elite strata. Most of the 10-11th century remains in the Carpathian Basin belong to common people, whose origin and relation to the immigrant elite has been widely debated. MethodsMitogenome sequences were determined from 202 individuals with Next Generation Sequencing combined with hybridization capture. Median Joining networks were used for phylogenetic analysis. The commoner population was compared to 87 ancient Eurasian populations with sequence based (Fst) and haplogroup based population genetic methods. ResultsHaplogroup composition of the commoner population markedly differs from the elite and in contrast to the elite, commoners cluster with European populations. Besides, detectable sub-haplogroup sharing indicates admixture between the elite and commoners. ConclusionsMajority of the 10-11th century commoners most likely represent local populations of the Carpathian Basin, which admixed with the eastern immigrant groups including conquering Hungarians.

genetics↗

Y-chromosome haplogroups from Hun, Avar and conquering Hungarian period nomadic people of the Carpathian Basin

Hun, Avar and conquering Hungarian nomadic groups arrived into the Carpathian Basin from the Eurasian Steppes and significantly influenced its political and ethnical landscape. In order to shed light on the genetic affinity of above groups we have determined Y chromosomal haplogroups and autosomal loci, from 49 individuals, supposed to represent military leaders. Haplogroups from the Hun-age are consistent with Xiongnu ancestry of European Huns. Most of the Avar-age individuals carry east Eurasian Y haplogroups typical for modern north-eastern Siberian and Buryat populations and their autosomal loci indicate mostly unmixed Asian characteristics. In contrast the conquering Hungarians seem to be a recently assembled population incorporating pure European, Asian and admixed components. Their heterogeneous paternal and maternal lineages indicate similar phylogeographic origin of males and females, derived from Central-Inner Asian and European Pontic Steppe sources. Composition of conquering Hungarian paternal lineages is very similar to that of Baskhirs, supporting historical sources that report identity of the two groups.

genetics↗

Mitogenomic data indicate admixture components of Asian Hun and Srubnaya origin in the Hungarian Conquerors

It has been widely accepted that the Finno-Ugric Hungarian language, originated from proto Uralic people, was brought into the Carpathian Basin by the Hungarian Conquerors. From the middle of the 19th century this view prevailed against the deep-rooted Hungarian Hun tradition, maintained in folk memory as well as in Hungarian and foreign written medieval sources, which claimed that Hungarians were kinsfolk of the Huns. In order to shed light on the genetic origin of the Conquerors we sequenced 102 mitogenomes from early Conqueror cemeteries and compared them to sequences of all available databases. We applied novel population genetic algorithms, named Shared Haplogroup Distance and MITOMIX, to reveal past admixture of maternal lineages. Phylogenetic and population genetic analysis indicated that more than one third of the Conqueror maternal lineages were derived from Central-Inner Asia and their most probable ultimate sources were the Asian Huns. The rest of the lineages most likely originated from the Bronze Age Potapovka-Poltavka-Srubnaya cultures of the Pontic-Caspian steppe, which area was part of the later European Hun empire. Our data give support to the Hungarian Hun tradition and provides indirect evidence for the genetic connection between Asian and European Huns. Available data imply that the Conquerors did not have a major contribution to the gene pool of the Carpathian Basin, raising doubts about the Conqueror origin of Hungarian language.

genetics↗

MITOMIX, an Algorithm to Reconstruct Population Admixture Histories Indicates Ancient European Ancestry of Modern Hungarians

By making use of the increasing number of available mitogenomes we propose a novel population genetic distance metric, named Shared Haplogroup Distance (SHD). Unlike FST, SHD is a true mathematical distance that complies with all metric axioms, which enables our new algorithm (MITOMIX) to detect population-level admixture based on SHD minimum optimization. In order to demonstrate the effectiveness of our methodology we analyzed the relation of 62 modern and 25 ancient Eurasian human populations, and compared our results with the most widely used FST calculation. We also sequenced and performed an in-depth analysis of 272 modern Hungarian mtDNA genomes to shed light on the genetic composition of modern Hungarians. MITOMIX analysis showed that in general admixture occurred between neighboring populations, but in some cases it also indicated admixture with migrating populations. SHD and MITOMIX analysis comply with known genetic data and shows that in case of closely related and/or admixing populations, SHD gives more realistic results and provides better resolution than FST. Our results suggest that the majority of modern Hungarian maternal lineages have Late Neolith/Bronze Age European origins (partially shared also with modern Danish, Belgian/Dutch and Basque populations), and a smaller fraction originates from surrounding (Serbian, Croatian, Slovakian, Romanian) populations. However only a minor genetic contribution (<3%) was identified from the IXth Hungarian Conquerors whom are deemed to have brought Hungarians to the Carpathian Basin. Our analysis shows that SHD and MITOMIX can augment previous methods by providing novel insights into past population processes.

genetics↗

Revising mtDNA haplotypes of the ancient Hungarian conquerors with next generation sequencing

As part of the effort to create a high resolution representative sequence database of the medieval Hungarian conquerors we have resequenced the entire mtDNA genome of 24 published ancient samples with Next Generation Sequencing, whose haplotypes had been previously determined with traditional PCR based methods. We show that PCR based methods are prone to erroneous haplotype or haplogroup determination due to ambiguous sequence reads, and many of the resequenced samples had been classified inaccurately. The SNaPshot method applied with published ancient DNA authenticity criteria is the most straightforward and cheapest PCR based approach for testing a large number of coding region SNP-s, which greatly facilitates correct haplogroup determination.

genetics↗