Biology subjects

Chen, P.-W.

Publications and source records attributed to Chen, P.-W..

4 recordsLinked to original sources

bioRxiv2026

MorphoANOVA: Dissecting Histology-Gene Expression Relationships in Spatial Transcriptomics

Spatial transcriptomics (ST) measures the expression of hundreds to thousands of genes within tissue architecture, often accompanied by histology images. However, it remains challenging to systematically characterize which genes exhibit associations with tissue morphology, whether these associations vary spatially, and which genes show additional spatial expression patterns beyond those captured by morphology. Here we introduce MorphoANOVA, a gene-wise statistical framework for characterizing morphology--expression relationships across genes measured by ST. Using nested spatially varying coefficient models and sequential ANOVA, MorphoANOVA assesses slide-wide associations with an H\&E-derived morphology feature, location-specific changes in these associations, and additional spatial variation after accounting for the selected feature. The resulting statistics enable gene prioritization and pathway enrichment analysis, while spatial component maps support the interpretation of individual genes. Simulations demonstrate MorphoANOVA's ability to distinguish the modeled components and recover their spatial patterns. Applications to human cortex and breast cancer identify biological programs associated with different morphology--expression patterns and reveal distinct relationships with cell composition. Across three HER2-positive breast cancer patients, invasive-cancer marker genes consistently exhibit stronger evidence of location-specific morphology associations. MorphoANOVA thus provides a framework for systematically interpreting spatial gene-expression patterns in relation to tissue morphology.

bioinformatics↗

bioRxiv2022

WGT: Tools and algorithms for recognizing, visualizing and generating Wheeler graphs

SummaryA Wheeler graph represents a collection of strings in a way that is particularly easy to index and query. Such a graph is a practical choice for representing a graph-shaped pangenome, and it is the foundation for current graph-based pangenome indexes. However, there are no practical tools to visualize or to check graphs that may have the Wheeler properties. Here we present Wheelie, an algorithm that combines a renaming heuristic with a permutation solver (Wheelie-PR) or a Satisfiability Modulo Theory (SMT) solver (Wheelie-SMT) to check whether a given graph has the Wheeler properties, a problem that is NP complete in general. Wheelie can check a variety of random and real-world graphs in far less time than any algorithm proposed to date. It can check a graph with 1,000s of nodes in seconds. We implement these algorithms together with complementary visualization tools in the WGT toolkit, available as open source software at https://github.com/Kuanhao-Chao/Wheeler_Graph_Toolkit.

bioinformatics↗

bioRxiv2022

Auxin Plays a Role in the Adaptation of Rice to Anaerobic Germination and Seedling Establishment

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies have shown that excessive levels of IAA frequently cause the inhibition of plant growth and development. In the present study, the high-level accumulation of endogenous IAA is observed under submergence in the dark, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. The OsGH3-8 encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3-8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. The present study reveals that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.

plant biology↗

bioRxiv2022

Subtyping of major SARS-CoV-2 variants reveals different transmission dynamics

SARS-CoV-2 continues to evolve, causing waves of the pandemic. Up to March 2022, eight million genome sequences have accumulated, which are classified into five major variants of concern. With the growing number of sequenced genomes, analysis of the big dataset has become increasingly challenging. Here we developed systematic approaches for comprehensive subtyping and pattern recognition for transmission dynamics. By analyzing the first two million viral genomes as of July 2021, we found that different subtypes of the same variant exhibited distinct temporal trajectories. For example, some Delta subtypes did not spread rapidly, while others did. We identified sets of characteristic single nucleotide variations (SNVs) that appeared to enhance transmission or decrease efficacy of antibodies for some subtypes of the Delta and Alpha variants. We also identified a set of SNVs that appeared to suppress transmission or increase viral sensitivity to antibodies. These findings are later confirmed in an analysis of six million genomes as of December 2021. For the Omicron variant, the dominant type in the world, we identified the subtypes with enhanced and suppressed transmission in an analysis of seven million genomes as of January 2022 and further confirmed the findings in a later analysis of eight million genomes as of March 2022. While the "enhancer" SNVs exhibited an enriched presence on the spike protein, the "suppressor" SNVs are mainly elsewhere. Disruption of the SNV correlation largely destroyed the enhancer-suppressor phenomena. These results suggest the importance of fine subtyping of variants, and point to potential complex interactions among SNVs.

bioinformatics↗