Biology subjects

Nakatsuka, N. J.

Publications and source records attributed to Nakatsuka, N. J..

3 recordsLinked to original sources

bioRxiv2024

A Reproducibility Focused Meta-Analysis Method for Single-Cell Transcriptomic Case-Control Studies Uncovers Robust Differentially Expressed Genes

We assessed the reproducibility of differentially expressed genes (DEGs) in previously published Alzheimers (AD), Parkinsons (PD), Huntingtons (HD), Schizophrenia (SCZ), and COVID-19 scRNA-seq studies. While transcriptional scores from DEGs of individual PD, HD, and COVID-19 datasets had moderate predictive power for case-control status of other datasets, genes from individual AD and SCZ datasets had poor predictive power. We developed a non-parametric meta-analysis method, SumRank, based on reproducibility of relative differential expression ranks across datasets, and found DEGs with improved predictive power. By multiple metrics, specificity and sensitivity of these genes were substantially higher than those discovered by dataset merging and inverse variance weighted p-value aggregation methods and had significant enrichment in snATAC-seq peaks and human disease gene associations. The DEGs revealed known and novel biological pathways, such as up-regulation of chaperone-mediated protein processing in PD glia and lipid transport in AD and PD microglia, and down-regulation of glutamatergic processes in AD astrocytes and glutamatergic neurons and synaptic processing and neuron projection genes in HD FOXP2 neurons. We find 56 DEGs shared amongst AD, PD, and HD, and validate BCAT1 as down-regulated in AD mouse oligodendrocytes. Lastly, we evaluate factors influencing reproducibility of individual studies as a prospective guide for experimental design.

genomics↗

bioRxiv2021

Ancient genomes reveal long range influence of the site and culture of Tiwanaku

Tiwanaku was a civilization that flourished in the Lake Titicaca Basin (present-day Bolivia) between 500 and 1000 CE. At its apogee, Tiwanaku controlled the lakes southern shores and influenced certain areas of the Southern Andes. There is a considerable amount of archaeological and anthropological data concerning the Tiwanaku culture; however, our understanding of the population of the site of Tiwanaku is limited. To understand the population dynamics at different stages of the Tiwanaku cultural development, we analyzed 17 low-coverage genomes from individuals dated between 300 and 1500 CE. We found that the population from the Lake Titicaca Basin remained genetically unchanged throughout more than 1200 years, indicating that significant cultural and political changes were not associated with large scale population movements. In contrast, individuals excavated from Tiwanakus ritual core were highly heterogeneous, some with genetic ancestry from as far away as the Amazon, supporting the proposition of foreign presence at the site. However, mixed-ancestry individuals presence suggests they were local descendants of incomers from afar rather than captives or visiting pilgrims. A number of human offerings from the Akapana Platform dating to ca. 950 CE mark the end of active construction and maintenance of the monumental core and the wane of Tiwanaku culture. Significance StatementTiwanaku was an important pre-Inca polity in South America and an example of primary social complexity on par with civilizations in the Indus and Nile river valley. Flourishing between 500 and 1000 CE, Tiwanaku exercised control in the south Titicaca basin and influenced a vast area in southern Peru, Bolivia, and northern Chile. Comprehensive archeological studies provided information about the rise, expansion, and fall of the Tiwanaku culture, but little is known about the monumental sites population. To address this lacuna, we generated low coverage genomes for 17 individuals, revealing that while the Titicaca basins residential population was homogenous, the individuals excavated from the ritual core of Tiwanaku drew their ancestry from distant regions.

genomics↗

bioRxiv2020

ContamLD: Estimation of Ancient Nuclear DNA Contamination Using Breakdown of Linkage Disequilibrium

We report a method, ContamLD, for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of contaminant DNA, leveraging the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors (e.g. less than 1.5% standard error in cases with <10% contamination and data from at least 500,000 sequences covering SNPs). This method is optimized for application to aDNA, leveraging characteristic aDNA damage patterns to provide calibrated contamination estimates. Availability: https://github.com/nathan-nakatsuka/ContamLD.

evolutionary biology↗