Biology subjects

han, y.

Publications and source records attributed to han, y..

3 recordsLinked to original sources

bioRxiv2024

AKR1C mediates the acquired resistance to T-Dxd in a HER-2 positive gastric cancer line

Trastuzumab deruxtecan (T-Dxd), an anti-HER2 antibody-drug conjugate, has significantly enhanced clinical outcomes for patients as a HER2-directed therapy compared to previous standards of care. However, acquired resistance is always a concern, necessitating further investigation into the underlying resistance mechanism. In this study, we successfully established T-Dxd-resistant cell line (N87-R) by exposing HER2-positive N87 gastric cancer cells to increasing concentrations of T-Dxd, and demonstrated its resistance phenotype both in vitro and in vivo. While there were no changes in HER2 expression or T-Dxd binding in N87-R, a signature of drug metabolism genes were found upregulated, among which AKR1C played a critical role in the resistance mechanism. The resistance phenotype of N87-R cells was mitigated by both siRNA-mediated knockdown of AKR1C and pharmacological inhibition of its enzymatic activity. Our preclinical study underscores the critical role of AKR1C function in mediating T-Dxd resistance and suggests potential therapeutic innovation for combating T-Dxd resistance.

cancer biology↗

bioRxiv2024

Complex genetic architecture underlying the plasticity of tobacco leaf width provides insight into across-environment genomic prediction

Phenotypic plasticity refers to the ability of a given genotype to produce multiple phenotypes in response to changing environmental conditions. Understanding the genetic basis of phenotypic plasticity and developing predictive models for agronomic traits are crucial for future agricultural adaptation to climate change. In this study, we investigated the genetic basis of leaf width mean (LWm) and plasticity (LWp) in a tobacco multiparent advanced generation inter-cross (MAGIC) population which consisting of 594 individuals. We identified 14 quantitative trait loci (QTLs) significantly associated with LWm, 43 with LWp. Our findings suggest that dynamic changes in QTL effects across environments, along with polygenic effects, may underlie the genetic basis of leaf width plasticity. Among them, qLW14 was narrowed down to a 3 Mb structural variation region. When this fragment was deleted in tobacco, plants exhibited increased leaf width, but only under specific environmental conditions. This finding suggests that the key gene within qLW14 may act as a negative regulator of leaf width through interactions with specific environmental factors. By integrating genetic diversity, environments variation, and their interactions into a GEAI model, we were able to build a framework for cross-environment prediction, improving prediction accuracy by 8.7% when compared to traditional model. Overall, this study highlights the complex genetic basis underlying LWp, involving multiple alleles and genotype-environment interactions. These findings provide valuable insights into the role of phenotypic plasticity in plant adaptation to environmental changes.

genetics↗

bioRxiv2024

EasyOmics-A graphical interface for population-scale omics data association, integration and visualization

The rapid growth of population-scale whole genome resequencing, RNA sequencing, bisulfate sequencing, metabolomics and proteomic profiling has led quantitative genetics into a big omics data era. Performing omics data association analysis, such as genome, transcriptome, proteome and methylome wide association analysis, and integrative analysis on multiple omics dataset requires various bioinformatics tools rely on advanced programming skills and command-line environments, which are challenging for most wet-lab biologists. Here, we present EasyOmics a stand-alone R Shiny application with a user-friendly interface for wet-lab biologists to perform population-scale omics data association, integration and visualization. The toolkit incorporates multiple functions designed to meet the increasing demand for big omics data analyses, ranging from data quality control, heritability estimation, genome wide association analysis, conditional association analysis, omics quantitative trait locus mapping, omics wide association analysis, omics data integration and data visualization etc. A wide variety of publication quality graphs can be prepared in EasyOmics using R plot engine with point-and-click. EasyOmics is a platform-independent software that can be run under all operating systems with a docker container for easy installation. It is freely available to non-commercial users at docker hub https://hub.docker.com/repository/docker/yuhan2000/gwas/general.

genetics↗