Biology subjects

Qin, G.

Publications and source records attributed to Qin, G..

42 records · Page 3Linked to original sources

bioRxiv2020

A functional module states framework reveals cell states for drug and target prediction

Cells are complex systems in which many functions are performed by different genetically-defined and encoded functional modules. To systematically understand how these modules respond to drug or genetic perturbations, we developed a Functional Module States framework. Using this framework, we 1) defined the drug induced transcriptional state space for breast cancer cell lines using large public gene expression datasets, and revealed that the transcriptional states are associated with drug concentration and drug targets; 2) identified potential targetable vulnerabilities through integrative analysis of transcriptional states after drug treatment and gene knockdown associated cancer dependency; and 3) used functional module states to predict transcriptional state-dependent drug sensitivity and built prediction models using the functional module states for drug response. This approach demonstrates a similar prediction performance as do approaches using high dimensional gene expression values, with the added advantage of more clearly revealing biologically relevant transcriptional states and key regulators.

systems biology↗

bioRxiv2020

MicroRNA775 Promotes Intrinsic Leaf Size and Reduces Cell Wall Pectin Level via a Target Galactosyltransferase in Arabidopsis

Plants possess unique primary cell walls made of complex polysaccharides that play critical roles in determining intrinsic cell and organ size. How genes responsible for synthesizing and modifying the polysaccharides are regulated by microRNAs (miRNAs) to control plant size remains largely unexplored. Here we identified 23 putative cell wall related miRNAs, termed CW-miRNAs, in Arabidopsis thaliana and characterized miR775 as an example. We showed that miR775 post-transcriptionally silences GALT9, which encodes an endomembrane-located galactosyltransferase belonging to the glycosyltransferase 31 family. Over-expression of miR775 and deletion of GALT9 significantly enlarged leaf-related organs, primarily owing to increases in cell size. Monosaccharide quantification, confocal Raman imaging, and immunolabelling combined with atomic force microscopy (AFM) revealed that the MIR775A-GALT9 circuit modulates pectin level and elastic modulus of the cell wall. We further showed that MIR775A is directly repressed by the transcription factor ELONGATED HYPOCOTYL 5 (HY5). Genetic analysis confirmed that HY5 is a negative regulator of leaf size and acts through the HY5-MIR775A-GALT9 repression cascade to control pectin level. These results demonstrate that miR775-regulated cell wall remodeling is an integral determinant for intrinsic leaf size in A. thaliana and highlight the need to study other CW-miRNAs for more insights into cell wall biology.

plant biology↗

bioRxiv2020

Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.

immunology↗

bioRxiv2020

A novel protein complex that regulates active DNA demethylation in Arabidopsis

Active DNA demethylation is critical for altering DNA methylation patterns and regulating gene expression. The 5-methylcytosine DNA glycosylase/lyase ROS1 initiates a base excision repair pathway for active DNA demethylation and is required for the prevention of DNA hypermethylation at thousands of genomic regions in Arabidopsis. How ROS1 is regulated and targeted to specific genomic regions is not well understood. Here, we report the discovery of an Arabidopsis protein complex that contains ROS1, regulates ROS1 gene expression, and likely targets the ROS1 protein to specific genomic regions. ROS1 physically interacts with a WD40 domain protein (RWD40), which in turn interacts with a methyl-DNA binding protein (RMB1) as well as with a zinc finger and homeobox domain protein (RHD1). RMB1 binds to DNA that is methylated in any sequence context, and this binding is necessary for its function in vivo.Loss-of-function mutations in RWD40, RMB1, or RHD1 cause DNA hypermethylation at several tested genomic regions independently of the known ROS1 regulator IDM1. Because the hypermethylated genomic regions include the DNA methylation monitoring sequence in the ROS1 promoter, plants mutated in RWD40, RMB1, or RHD1 show increased ROS1 expression. Importantly, ROS1 binding to the ROS1 promoter requires RWD40, RMB1, and RHD1, suggesting that this complex dictates ROS1 targeting to this locus. Our results demonstrate that ROS1 forms a protein complex with RWD40, RMB1, and RHD1, and that this novel complex regulates active DNA demethylation at several endogenous loci in Arabidopsis.

plant biology↗

bioRxiv2019

Transcriptome analysis of the Larimichthys polyactis under heat and cold stress

The small yellow croaker (Larimichthys polyactis) is an important marine economic fish that is widely distributed in the East Sea, Yellow Sea and Bohai of China. However, the wild populations of small yellow croaker are severely depleted, and there is currently a developing large-scale artificial propagation of this fish for aquaculture. However, the current variety of small yellow croaker that is cultivated is not capable to coping with large fluctuations in temperature. Therefore, it is important to understand the molecular mechanisms that are activated in response to temperature stress in the small yellow croaker. Here, we conducted transcriptomic analysis of the liver of small yellow croaker under heat and cold stress. A total of 270,844,888, 265,727,006 and 259,666,218 clean reads were generated from heat temperature group, low temperature group and control group, respectively, and comparing expression of genes in these transcriptomes,10,878 unigenes that were differential expressed were identified. Sixteen of the differentially expressed unigenes were validated by qRT-PCR. Pathway enrichment analysis identified that the ER pathway, immune signaling pathway and metabolic response pathway were affected by temperature stress. The results of this study provide a comprehensive overview of temperature stress-induced transcriptional patterns in liver tissues of the small yellow croaker. In addition, these results can guide future molecular studies of heat and cold stress response in this species for improving the stock used for aquaculture.

physiology↗

bioRxiv2019

Kinetic Inference Resolves Epigenetic Mechanism of Drug Resistance in Melanoma

Drug-induced dedifferentiation towards a drug-tolerant persister state is a common mechanism cancer cells exploit to escape therapies, posing a significant obstacle to sustained therapeutic efficacy. The dynamic coordination of epigenomic and transcriptomic programs at the early-stage of drug exposure, which initiates and orchestrates these reversible dedifferentiation events, remains largely unexplored. Here we employ high-temporal-resolution multi-omics profiling, information-theoretic approaches, and dynamic system modeling to probe these processes in BRAF-mutant melanoma models and patient specimens. We uncover a hysteretic transition trajectory of melanoma cells in response to oncogene inhibition and subsequent release, driven by the sequential operation of two tightly coupled transcriptional waves, which orchestrate genome-scale chromatin state reconfiguration. Modeling of the transcriptional wave interactions predicts NF-{kappa}B/RelA-driven chromatin remodeling as the underlying mechanism of cell-state dedifferentiation, a finding we validate experimentally. Our results identify critical RelA-target genes that are epigenetically modulated to drive this process, establishing a quantitative epigenome gauge to measure cell-state plasticity in melanomas, which supports the potential use of drugs targeting epigenetic machineries to potentiate oncogene inhibition. Extending our investigation to other cancer models, we identify oxidative stress-mediated NF-{kappa}B/RelA activation as a common mechanism driving cellular transitions towards drug-tolerant persister states, revealing a novel and pivotal role for the NF-{kappa}B signaling axis in linking cellular oxidative stress to cancer progression.

cancer biology↗