Biology subjects

Yao, N.

Publications and source records attributed to Yao, N..

11 recordsLinked to original sources

bioRxiv2026

Determining cellular phylogeny and migration at high resolution in spatial genomics

Cellular migration and tumor evolution are central to tissue homeostasis and cancer biology. Rapid advances in spatial genomics have raised the possibility of using somatic mutations to track these processes in situ in human tissues. However, frequent data dropouts in spatial genomics measurements make this challenging to implement. Here, we present StarTrak (SpaTial Analysis for lineage ReconsTRuction with somatic vAriant calling and tracKing), a framework for somatic variant calling and lineage reconstruction at single-pixel spatial resolution. StarTrak employs a neural network framework to integrate mutational evidence (from both nuclear and mitochondrial reads), spatial proximity, histological images, and transcriptomic states to identify spatially informative patterns of mutations. It performs robustly across tissue types and spatial-omics platforms (being particularly successful with spatial ATAC-seq). Applying StarTrak to tumor sections, we infer the migration of mutated tumor cells into adjacent non-malignant tissues and reconstruct distinct lineage trees associated with different spatial regions. Notably, we identify tumor regions with nearly identical transcriptomic states but distinct mutational profiles. Moreover, for skin sections, StarTrak identifies sunlight-associated mutations in non-malignant epidermis and evidence suggesting the migration of these mutant surface cells into deeper skin layers. Overall, by integrating mutation calling with spatial context, StarTrak enables the inference of spatially resolved cellular migration and cellular phylogeny.

bioinformatics↗

bioRxiv2026

Genetic and epigenetic divergence among Arabidopsis thaliana Col-0 laboratory lineages since the 1950s

The model plant Arabidopsis thaliana has been a workhorse of plant biology since the 1950s, when the Columbia-0 (Col-0) accession was widely adopted by the research community as a reference genotype. Since then, Col-0 seeds have been shared among laboratories worldwide and propagated independently, creating a network of related laboratory lineages. Here, we sequenced the genomes and DNA methylomes of 78 Col-0 strains from laboratories and stock centers around the world to assess the genetic and epigenetic variation accumulated during this period and to reconstruct their propagation history from de novo variants. After quality filtering, we identified 1,415 single-nucleotide polymorphisms and 169,677 epimutations across 75 Col-0 lines and used these variants to generate SNP- and epimutation-based phylogenies. The two phylogenies showed highly concordant topologies, but the epimutation-based tree provided greater resolution of relationships among closely related lineages. Divergence-time estimates suggest that many lines have been propagated for approximately one generation per year over several decades, resulting in pairwise divergences of up to approximately 100 generations. We further identified 170 nonsynonymous substitutions and more than 200 candidate epialleles, some of which were associated with gene-expression differences among Col-0 clades and may therefore have functional consequences. Together, these findings show that Col-0 is best viewed not as a single invariant reference genotype, but as a collection of related laboratory lineages that have accumulated genetic, epigenetic, and transcriptional divergence through time, with potential consequences for the reproducibility of experiments across laboratories. Significance StatementThe Arabidopsis Col-0 reference accession is often treated as a single, invariant genotype, yet independently maintained laboratory stocks have accumulated substantial genetic, epigenetic, and transcriptional divergence since the 1950s. Some lineages are separated by more than 100 generations of independent propagation. Mutations and CG epimutations reconstruct nearly identical lineage histories, demonstrating that heritable DNA methylation changes provide a robust record of recent laboratory evolution.

genetics↗

bioRxiv2023

Chromosome-scale assembly of the African yam bean genome

Genomics-informed breeding of locally adapted, nutritious, albeit underutilised African crops can help mitigate food and nutrition insecurity challenges in Africa, particularly against the backdrop of climate change. However, utilisation of modern crop improvement tools including genomic selection and genome editing for many African indigenous crops is hampered by the scarcity of genetic and genomic resources. Here we report on the assembly of the genome of African yam bean (Sphenostylis stenocarpa), a tuberous legume crop that is indigenous to Africa. By combining long and short read sequencing with Hi-C scaffolding, we produced a chromosome-scale assembly with an N50 of 69.5 Mbp and totalling 649 Mbp in length (77 - 81% of the estimated genome size based on flow cytometry). Using transcriptome evidence from Nanopore RNA-Seq and homology evidence from related crops, we annotated 31,614 putative protein coding genes. We further show how this resource improves anchoring of markers, genome-wide association analysis and candidate gene analyses in Africa yam bean. This genome assembly provides a valuable resource for genetic research in Africa yam bean.

genomics↗

bioRxiv2023

An evolutionary epigenetic clock in plants

Molecular clocks are the basis for dating the divergence between lineages over macro-evolutionary timescales (~105-108 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes possess a clock-like behavior. This epimutation-clock is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation-clocks recapitulate known topologies and branching times of intra-species phylogenetic trees in the selfing plant A. thaliana and the clonal seagrass Z. marina, which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.

evolutionary biology↗

bioRxiv2021

Spatially-resolved transcriptomics analyses of invasive fronts in solid tumors

Solid tumors are complex ecosystems, and heterogeneity is the major challenge for overcoming tumor relapse and metastasis. Uncovering the spatial heterogeneity of cell types and functional states in tumors is essential for developing effective treatment, especially in invasive fronts of tumor, the most active region for tumor cells infiltration and invasion. We firstly used SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq) with a nanoscale resolution to characterize the tumor microenvironment of intrahepatic cholangiocarcinoma (ICC). Enrichment of distinctive immune cells, suppressive immune microenvironment and metabolic reprogramming of tumor cells were identified in the 500{micro}m-wide zone centered bilaterally on the tumor boundary, namely invasive fronts of tumor. Furthermore, we found the damaged states of hepatocytes with overexpression of Serum Amyloid A (SAA) in invasive fronts, recruiting macrophages for facilitating further tumor invasion, and thus resulting in a worse prognosis. We also confirmed these findings in hepatocellular carcinoma and other liver metastatic cancers. Our work highlights the remarkable potential of high-resolution-spatially resolved transcriptomic approaches to provide meaningful biological insights for comprehensively dissecting the tumor ecosystem and guiding the development of novel therapeutic strategies for solid tumors.

cancer biology↗

bioRxiv2021

OsMADS58 stabilizes gene regulatory circuits during rice stamen development

Rice (Oryza sativa) OsMADS58 is a C-class MADS box protein, and characterization of a transposon insertion mutant osmads58 suggested that OsMADS58 plays a role in stamen development. However, as no null mutation has been obtained, its role has remained unclear. Here, we report that the CRISPR knockout mutant osmads58 exhibits complex altered phenotypes, including anomalous diploid germ cell differentiation, aberrant meiosis, and delayed tapetum degeneration. This CRISPR mutant line exhibited stronger changes in expression of OsMADS58 target genes compared with the osmads58 dSpm (transposon insertion) line, along with changes in multiple pathways related to early stamen development. Notably, transcriptional regulatory circuits in young panicles covering the stamen at stages 4-6 were substantially altered in the CRISPR line compared to the dSpm line. These findings strongly suggest that the pleiotropic effects of OsMADS58 on stamen development derive from a potential role in stabilizing gene regulatory circuits during early stamen development. Thus, this work opens new avenues for viewing and deciphering the regulatory mechanisms of early stamen development from a network perspective.

plant biology↗

bioRxiv2020

Allelic diversity study of functional genes in East Africa bread wheat highlights opportunities for genetic improvement.

Wheat (Triticum aestivum L.) is a major staple crop in East Africa (EA) providing 9% and 10% of daily calories and protein intake, respectively. However, EA countries depend on import to meet 55% of their domestic wheat supplies due to increasing demands and low domestic yields. To determine the beneficial gene pool currently exploited for wheat improvement in EA, we examined the allelic diversity of 42 genes of breeding importance in a collection of 239 wheat cultivars and breeding lines from Kenya and Ethiopia using KASP markers. The assayed genes have been shown to control variations in plant height, thousand kernel weight (TKW), grain protein content, pre-harvest sprouting (PHS), disease resistance and flowering time. We observed the beneficial alleles of some major genes including Rht-D1, Gpc-B1, Yr5, Yr15, Sr26, and Fhb1 to be missing or present at low frequencies in this population. Furthermore, we validated the effects of the major Rht-1 alleles and TaCKX-6A in controlling variation in plant height and thousand kernel weight, respectively, under EA conditions. Our results uncover hitherto unexploited allelic diversity that can be used to improve the genetic potential of EA wheat germplasm. This will inform strategies to rapidly mobilize these beneficial alleles for wheat improvement in EA.

genetics↗

bioRxiv2019

High Yield Monolayer Graphene Grids for Near-Atomic Resolution Cryo-Electron Microscopy

Cryogenic electron microscopy (cryo-EM) has become one of the most powerful techniques to reveal the atomic structures and working mechanisms of biological macromolecules. New designs of the cryo-EM grids--aimed at preserving thin, uniform vitrified ice and improving protein adsorption--have been considered a promising approach to achieving higher resolution with the minimal amount of materials and data. Here, we describe a method for preparing graphene cryo-EM grids with 99% monolayer graphene coverage that allows for more than 70% grid squares for effective data acquisition with improved image quality and protein density. Using our graphene grids, we have achieved 2.6 [A] resolution for streptavidin, with a molecular weight of 52 kDa, from 11,000 particles. Our graphene grids increase the density of examined soluble, membrane, and lipo-proteins by at least five times, affording the opportunity for structural investigation of challenging proteins which cannot be produced in large quantity. In addition, our method employs only simple tools that most structural biology laboratories can access. Moreover, our approach allows for customized grid designs targeting specific proteins, due to its broad compatibility with a variety of nanomaterials. Significance statementSingle particle cryogenic electron microscopy (cryo-EM) represents the cutting-edge technology to determine three-dimensional atomic structures of bio-macromolecules. However, issues of cryo-sample preparation limit the cryo-EM to achieve higher resolution. Here, we demonstrated a high yield, monolayer graphene supporting film to improve the cryo-sample quality. Using our approach, we have achieved so far, the highest resolution structure of the smallest protein by cryo-EM with the minimal number of datasets. Our technique paves the way for universal cryo-sample preparation for near-atomic resolution cryo-EM.

biophysics↗

bioRxiv2019

Genetic diversity and population structure of indigenous chicken in Rwanda using microsatellite markers

Rwanda has about 4.5 million of indigenous chicken (IC) that are very low in productivity. To initiate any genetic improvement programme, IC needs to be accurately characterized. The key purpose of this study was to ascertain the genetic diversity of IC in Rwanda using microsatellite markers. Blood samples of IC sampled from 5 agro-ecological zones were collected from which DNA was extracted, amplified by PCR and genotyped using 28 microsatellite markers. A total of 325 (313 indigenous and 12 exotic) chicken were genotyped and revealed a total number of 305 alleles varying between 2 and 22 with a mean of 10.89 per locus. 186 distinct alleles and 60 private alleles were also observed. The frequency of private alleles was highest in samples from the Eastern region, whereas those from the North West had the lowest. The influx of genes was lower in the Eastern agro-ecological zone than the North West. The mean observed heterozygosity was 0.6155, whereas the average expected heterozygosity was 0.688. The overall inbreeding coefficient among the population was 0.040. Divergence from the Hardy-Weinberg equilibrium was significant in 90% of loci in all the populations. The analysis of molecular variance revealed that about 92% of the total variation originated from variation within populations. Additionally, the study demonstrated that IC in Rwanda could be clustered into four gene groups. In conclusion, there was considerable genetic diversity in IC in Rwanda, which represents a crucial genetic resource that can be conserved or optimized through genetic improvement.

genetics↗

bioRxiv2019

Construction of synthetic microbiota for reproducible flavor metabolism in Chinese light aroma type liquor produced by solid-state fermentation

Natural microbiota plays an essential role in flavor compounds producing for traditional food fermentation. Whereas, the fluctuation of natural microbiota results in the inconstancy of food quality. Thus, it is critical to reveal the core microbiota for flavor compounds producing and construct a synthetic core microbiota for constant food fermentation. Here, we revealed the core microbiota based on their flavor-producing and co-occurrence performance, using Chinese light aroma type liquor as a model system. Five genera were identified to be the core microbiota, including Lactobacillus, Saccharomyces, Pichia, Geotrichum, and Candida. The synthetic core microbiota of these five genera presented a reproducible dynamic profile with that in the natural microbiota. Monte Carlo test showed that the interpretation of five environmental factors (lactic acid, ethanol and acetic acid contents, moisture and pH) on the synthetic microbiota distribution were highly significant (P < 0.01), which was similar with that in the natural fermentation system. In addition, 77.27% of the flavor compounds produced by the synthetic core microbiota showed a similar dynamic profile ({rho} > 0) with that in the natural liquor fermentation process, and the flavor profile presented a similar composition. It indicated that the synthetic core microbiota is efficient for reproducible flavor metabolism. This work established a method for identifying core microbiota and constructing a synthetic microbiota for reproducible flavor compounds. It is of great significance for the tractable and constant production of various fermented foods.\n\nIMPORTANCEThe transformation from natural fermentation to synthetic fermentation is essential to construct a constant food fermentation process, which is the premise for stably making high-quality food. According to the functions of flavor-producing and co-occurring in dominant microbes, we provided a system-level approach to identify the core microbiota in Chinese light aroma type liquor fermentation. In addition, we successfully constructed a synthetic core microbiota to simulate the microbial community succession and flavor compounds production in the in vitro system. The constructed synthetic core microbiota could not only facilitate a mechanistic understanding of the structure and function of the microbiota, but also be beneficial for constructing a tractable and reproducible food fermentation process.

microbiology↗

bioRxiv2017

PRS-on-Spark: a novel, efficient and flexible approach for generating polygenic risk scores

MotivationPolygenic risk scores describe the genomic contribution to complex phenotypes and consistently account for a larger proportion of the variance than single nucleotide polymorphisms alone. However, there is little consensus on the optimal data input for generating polygenic risk scores and existing approaches largely preclude the use of imputed posterior probabilities and strand-ambiguous SNPs.\n\nResultsWe developed PRS-on-Spark (PRSoS) a polygenic risk score software implemented in Apache Spark and Python that accommodates a variety of data input (e.g., observed genotypes, imputed genotypes, or imputed posterior probabilities) and strand-ambiguous SNPs. We show that PRSoS is flexible and efficient and computes polygenic risk scores at a range of p-value thresholds more quickly than existing software (PRSice). We also show that the use of imputed posterior probabilities and the inclusion of strand-ambiguous SNPs increases the proportion of variance explained by polygenic risk scores for major depression.\n\nAvailability and ImplementationPRSoS is written in Apache Spark and Python and is freely available (see https://github.com/MeaneyLab/PRSoS).

bioinformatics↗