Biology subjects

Zhou, J. J.

Publications and source records attributed to Zhou, J. J..

6 recordsLinked to original sources

bioRxiv2023

Hierarchical Clustering and Omics Analysis Revealed Massive Molecular Shifts in a Tree under Combined Hypoxia and Salinity

Field and Greenhouse studies that attempted to describe the molecular responses of trees under waterlogging (WL) combined with salinity (ST) are quasi-inexistent. To dissect plant-specific molecular responses and patterns under SWL, we integrated transcriptional and metabolic analyses involving common differentially expressed genes (DEGs) and metabolites (DMs) patterns in Dalbergia odorifera leaflets. SWL-treated seedlings exhibited an impressively high number of DEGs and DMs compared to ST or WL. Although the main common DEGs and DMs showed a neutral pattern, gene ontology enrichment following the classification in different functional categories of SWL-transcripts displayed a predominant synergistic pattern mode. Hierarchical and silhouette analysis regrouped different morpho-physiological clusters following the treatment, SWL was mainly grouped with both single stress. SWL induced a massive shutdown of the photosynthesis apparatus through LHCBs- and PSA-related genes. Starch and plastoglobuli synthesis appeared to be drastically affected by SWL, while ABA content confirmed by ABA synthesis related-genes (ABF, ABA1 and NCED) variations showed a less-needed role. NXN (Nucleoredoxin) genes are the main factors that sustain the antioxidant system under SWL. Here we provide the first molecular responses, characterization and patterns of a tree under SWL that would significantly shed light on our understanding of the molecular mechanisms underlying combined stress.

plant biology↗

bioRxiv2022

Design Principles for Inflammasome Inhibition by Pyrin-Only-Proteins

Inflammasomes are filamentous signaling platforms essential for host defense against various intracellular calamities such as pathogen invasion and genotoxic stresses. However, dysregulated inflammasomes cause an array of human diseases including autoinflammatory disorders and cancer. It was recently identified that endogenous pyrin-only-proteins (POPs) regulate inflammasomes by directly inhibiting their filament assembly. Here, by combining Rosetta in silico, in vitro, and in cellulo methods, we investigate the target specificity and inhibition mechanisms of POPs. In contrast to a previous report, we find that POP1 is a poor inhibitor of the central inflammasome adaptor ASC. Instead, POP1 inhibits the assembly of upstream receptor PYD filaments such as those of AIM2, IFI16, NLRP3, and NLRP6. Moreover, not only does POP2 directly suppress the nucleation of ASC, but it can also inhibit the elongation of receptor filaments. In addition to inhibiting the elongation of AIM2 and NLRP6 filaments, POP3 potently suppresses the nucleation of ASC. Our Rosetta analyses and biochemical experiments consistently suggest that a combination of favorable and unfavorable interactions between POPs and PYDs is necessary for effective recognition and inhibition. Together, we reveal the intrinsic target redundancy of POPs and their inhibitory mechanisms.

biochemistry↗

bioRxiv2022

Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis

Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.

genomics↗

bioRxiv2021

Multivariate Genomewide Association Analysis with IHT

1In genome-wide association studies (GWAS), analyzing multiple correlated traits is potentially superior to conducting multiple univariate analyses. Standard methods for multivariate GWAS operate marker-by-marker and are computationally intensive. We present a penalized regression algorithm for multivariate GWAS based on iterative hard thresholding (IHT) and implement it in a convenient Julia package MendelIHT.jl (https://github.com/OpenMendel/MendelIHT.jl). In simulation studies with up to 100 traits, IHT exhibits similar true positive rates, smaller false positive rates, and faster execution times than GEMMAs linear mixed models and mv-PLINKs canonical correlation analysis. On UK Biobank data, our IHT software completed a 3-trait joint analysis in 20 hours and an 18-trait joint analysis in 53 hours, requiring up to 80GB of computer memory. In short, our software enables geneticists to fit a single regression model that simultaneously considers the effect of all SNPs and dozens of traits.

genetics↗

bioRxiv2018

BodyMap transcriptomes reveal unique circular RNA features across tissue types and developmental stages

Circular RNAs (circRNAs) are a novel class of regulatory RNAs. Here, we present a comprehensive investigation of circRNA expression profiles across 11 tissues and 4 developmental stages in rats, along with cross-species analyses in humans and mice. Although positively correlated, circRNAs exhibit higher tissue specificity than cognate mRNAs. Also, genes with higher expression levels exhibit a larger fraction of spliced circular transcripts than their linear counterparts. Intriguingly, while we observed a monotonic increase of circRNA abundance with age in the rat brain, we further discovered a dynamic, age-dependent pattern of circRNA expression in the testes that is characterized by a dramatic increase with advancing stages of sexual maturity and a decrease with aging. The age-sensitive testicular circRNAs are highly associated with spermatogenesis, independent of cognate mRNA expression. The tissue/age implications of circRNAs suggest that they present unique physiological functions rather than simply occurring as occasional by-products of gene transcription.

bioinformatics↗

bioRxiv2018

Exact Tests of Zero Variance Component in Presence of Multiple VarianceComponents with Application to Longitudinal Microbiome Study

In the metagenomics studies, testing the association of microbiome composition and clinical conditions translates to testing the nullity of variance components. Computationally efficient score tests have been the major tools. But they can only apply to the null hypothesis with a single variance component and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to solve the problems of (1) testing the association of the overall microbiome composition in a longitudinal design and (2) detecting the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of human immunodeficiency virus (HIV) infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed lights on the impact of lung microbiome to HIV complexities. The method is implemented in the open source, high-performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.

genomics↗