Biology subjects

Di, M.

Publications and source records attributed to Di, M..

4 recordsLinked to original sources

bioRxiv2025

Alpha diversity analysis of hepatic transcriptome reveals novel pathways inalcohol-related hepatitis

Next generation sequencing can identify novel gene expression patterns in disease. Beyond differentially expressed genes analysis, we investigated the ability of within-population diversity (-diversity) of the transcriptome to reveal new biological information in alcohol-related liver disease (ALD), comparing Differential Shannon diversity (DSD) to transcriptome heterogeneity changes. RNA sequencing data from normal livers and patients with early silent ALD and severe AH were analyzed. -diversity indices and Percent Shannon Diversity of a gene, which refers to this genes contribution to total Shannon entropy were calculated. Ingenuity pathway analysis identified canonical pathways determined by differentially expressed genes (DEG) and DSD approaches. ALD significantly decreased hepatic transcriptome -diversity correlating with increased relative contribution of select genes. These changes were driven by lower abundance gene expression loss. DEG and DSD analyses showed overlapping genes and canonical pathways, but DSD also identified novel genes and pathways not highlighted by DEG. Importantly, DSD more effectively identified differences between preclinical ALD and AH severity stages. ALD decreases hepatic transcriptome heterogeneity, favoring pathways associated with organ damage or damage response. Preclinical and clinical ALD led to differential heterogeneity patterns that may provide new disease insights. DSD analysis identified enriched pathways missed by standard DEG analyses, potentially yielding novel insight into disease mechanisms and biomarkers. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=53 SRC="FIGDIR/small/681263v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@d2d3a3org.highwire.dtl.DTLVardef@14496a8org.highwire.dtl.DTLVardef@1ff0dfeorg.highwire.dtl.DTLVardef@1efa8f3_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2023

Expanding RNA editing toolkit using an IDR-based strategy

RNA base editors should ideally be free of immunogenicity, compact, efficient and specific, which has not been achieved for C>U editing. Here we first describe a compact C>U editor entirely of human origin, created by fusing the human C>U editing enzyme RESCUE-S to CIRTS, a tiny, human-originated programmable RNA binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short Histidine-Rich Domain (HRD), which is derived from the Internal Disordered Region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C>U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C>U RNA base editors.

molecular biology↗

bioRxiv2022

Towards Hierarchical Causal Representation Learning for Nonstationary Multi-Omics Data

Though open chromatin may promote active transcription, gene expression responses may not be directly coordinated with changes in chromatin accessibility. Most existing methods for single-cell multi-omics data focus only on learning stationary and shared information among these modalities, overlooking modality-specific information delineating cellular states and dynamics resulting from causal relations among modalities. To account for this, the epigenome and transcriptome relationship can be characterized in relation to time as "coupled" (changing dependently) or "decoupled" (changing independently). We propose the framework HALO, which adopts a causal approach to model these temporal causal relations on two levels. On the representation level, HALO factorizes these two modalities into both coupled and decoupled latent representations, identifying the dynamic interplay between chromatin accessibility and transcription through temporal modulations in the latent space. On the individual gene level, HALO matches gene-peak pairs and characterizes changing dynamics between gene expression and local peaks with time. HALO reveals bipotency in a subset of AT2 cells that exhibit different decisions in lineage specification between systemic sclerosis (SSc) and normal conditions. We demonstrate that using coupled and decoupled information, HALO discovers analogous biological functions between modalities, distinguishes epigenetic factors for lineage specification, and identifies temporal cis-regulation interactions relevant to cellular differentiation and complex human diseases.

bioinformatics↗

bioRxiv2022

Plastid-specific RsmD methyltransferase and ribosome maturation factor RimM are crucial for 16S rRNA maturation and proteostasis

Chloroplast pre-ribosomal RNA (rRNA) undergoes maturation, which is critical for ribosome assembly. While the central and auxiliary factors in rRNA maturation have been elucidated in bacteria, their mode of action remains largely unexplored in chloroplasts. We now reveal chloroplast-specific factors involved in 16S rRNA maturation, RsmD methyltransferase (AtRsmD) and ribosome maturation factor RimM-like protein (AtRimM) in Arabidopsis thaliana. A forward genetic screen aimed to find suppressors of the Arabidopsis yellow variegated 2 (var2) mutant defective in photosystem II (PSII) quality control found a causal nonsense mutation in AtRsmD. The substantially impaired 16S rRNA maturation and translation due to the mutation rescued the leaf variegation phenotype by lowering the levels of PSII core proteins in var2. The subsequent co-immunoprecipitation coupled with mass spectrometry analyses and bimolecular fluorescence complementation assay found that AtRsmD interacts with AtRimM. Consistent with their interaction, loss of AtRimM also considerably impairs 16S rRNA maturation, with less methylation in m2G915 in 16S rRNA catalyzed by AtRsmD. The atrimM mutation also rescued var2 mutant phenotypes, corroborating the functional interplay between AtRsmD and AtRimM towards 16S rRNA maturation and chloroplast proteostasis.

plant biology↗