Biology subjects

Chen, J.-Q.

Publications and source records attributed to Chen, J.-Q..

8 recordsLinked to original sources

bioRxiv2025

A high-throughput methods SNIPR-Nm reveals small RNA methylation ratio

Small RNAs regulate gene expression and genome stability, and their functions are shaped by 3'-terminal 2'-O-methylation (Nm). Although Nm is universal in plants and mainly marks animal piRNAs, recent evidence reveals Nm on mammalian miRNAs, highlighting broader regulatory roles. However, current sequencing underestimates Nm-modified RNAs due to ligation bias, and existing qPCR-based methods cannot simultaneously quantify abundance and modification, leaving Nm dynamics largely unexplored. We developed a unified enzymatic strategy that integrates poly(A) polymerase and a thermostable ligase to measure both small RNA abundance and 3'-end Nm status. Applied to mouse testis, it enables robust quantification of Nm ratios for piRNAs and miRNAs. Our method offers a versatile tool for dissecting small RNA methylation in development and disease.

genetics↗

bioRxiv2022

Assessment of Emerging Pretraining Strategies in Interpretable Multimodal Deep Learning for Cancer Prognostication

Deep learning models have demonstrated the remarkable ability to infer cancer patient prognosis from molecular and anatomic pathology information. Studies in recent years have demonstrated that leveraging information from complementary multimodal data can improve prognostication, further illustrating the potential utility of such methods. Model interpretation is crucial for facilitating the clinical adoption of deep learning methods by fostering practitioner understanding and trust in the technology. However, while prior works have presented novel multimodal neural network architectures as means to improve prognostication performance, these approaches: 1) do not comprehensively leverage biological and histomorphological relationships and 2) make use of emerging strategies to "pretrain" models (i.e., train models on a slightly orthogonal dataset/modeling objective) which may aid prognostication by reducing the amount of information required for achieving optimal performance. Here, we develop an interpretable multimodal modeling framework that combines DNA methylation, gene expression, and histopathology (i.e., tissue slides) data, and we compare the performances of crossmodal pretraining, contrastive learning, and transfer learning versus the standard procedure in this context. Our models outperform the existing state-of-the-art method (average 11.54% C-index increase), and baseline clinically driven models. Our results demonstrate that the selection of pretraining strategies is crucial for obtaining highly accurate prognostication models, even more so than devising an innovative model architecture, and further emphasize the all-important role of the tumor microenvironment on disease progression.

pathology↗

bioRxiv2022

Gut Microbiome Contributes to Cold-climate Adaptation in Lizards

The metabolic cold-climate adaption hypothesis predicts that animals from cold environments have relatively high metabolic rates compared with their warm-climate counterparts. However, studies testing this hypothesis are sparse. Here, we compared gut microbes between two cold-climate lizard species of the genus Phrynocephalus to test the hypothesis that gut microbiota can help lizards adapt to cold environments by promoting metabolism and absorption efficiency. We kept lizards at 24{degrees}C and 30{degrees}C for 25 d, and then collected their fecal samples to analyze and compare the microbiota based on 16S rRNA gene sequencing technology. The gut microbiota was mainly composed of Proteobacteria, Firmicutes, Bacteroidetes, and Verrucomicrobia at the phylum level in both species (Proteobacteria > Firmicutes > Verrucomicrobiota in P. erythrurus, and Bacteroidota > Proteobacteria > Firmicutes in P. przewalskii). Further analysis revealed that the gut microbiota contributed to the hosts cold adaptation, but with differences in the relative abundance of these contributory bacteria between the two species. KEGG analysis revealed that the gut microbiota primarily played roles in metabolism, genetic information processing, cellular processes, and environmental information processing in both species. Furthermore, genes related to metabolism were more abundant in P. erythrurus at 24 {degrees}C than in other species x temperature combinations, indicating the role of gut microbiota in long-term cold-climate adaptation. Our finding that gut microbiome contributes to cold-climate adaptation in both species but more evidently in P. erythrurus using colder habitats than P. przewalskii throughout a year confirms the gut microbiotas role in the cold-climate adaptation in lizards. IMPORTANCEThis study proves that temperature affects the composition and relative abundance of the gut microbiota in two Phrynocephalus lizards in a species-specific manner. Both species harbor specific gut microbiota with significant roles in cold-climate adaptation. Specifically, P. erythrurus has a higher Proteobacteria ratio and relative abundance of metabolism-related microbial genes in the gut than P. przewalskii. Given that P. erythrurus uses colder habitats than P. przewalskii throughout a year, these results suggest that gut microbiota contributes to cold-climate adaptation in both species lizards but more evidently in P. erythrurus. This study provides evidence linking gut microbiome with cold adaptation. The co-evolution mechanism between gut microbiota and their hosts in extreme environments will provide new insights into animal adaptation.

ecology↗

bioRxiv2021

An angiosperm NLR atlas reveals that NLR gene reduction is associated with ecological specialization and signal transduction component deletion

Nucleotide-binding site-leucine-rich repeat receptor (NLR) genes comprise the largest family of plant disease resistance genes. NLR genes are phylogenetically divided into the TNL, CNL, and RNL subclasses. NLR copy numbers and subclass composition vary tremendously across angiosperm genomes. However, the evolutionary associations between genomic NLR content and plant lifestyle, or between NLR content and signal transduction components, are poorly characterized due to limited genome availability. Here, we established an angiosperm NLR atlas (ANNA, http://compbio.nju.edu.cn/app/ANNA/), which includes NLR genes from over 300 angiosperm genomes. Using ANNA, we revealed that NLR copy numbers differ up to 66-fold among closely related species due to rapid gene loss and gain. Interestingly, NLR contraction was associated with adaptations to aquatic, parasitic, and carnivorous lifestyles. The convergent NLR reduction in aquatic plants resembles the long-term evolutionary silence of NLR genes in green algae before the colonization of land. A co-evolutionary pattern between NLR subclasses and plant immune-pathway components was also identified, suggesting that immune pathway deficiencies may drive TNL loss. Finally, we recovered a conserved TNL lineage that may function independently of the RNL pathway. Our findings provide new insights into the evolution of NLR genes in the context of plant lifestyles and genome content variation.

plant biology↗

bioRxiv2020

Inhibition of Pten activity promotes IB4 positive sensory neuronal axon growth

Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduce total PTEN expression in adult sensory neurons, however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

neuroscience↗

bioRxiv2020

Identification and exploration of 2'-O-methylation sites in rRNA and mRNA with a novel RNase based platform

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain largely unknown due to the lack of accurate and efficient identification tools. To overcome this gap, we established NJU-seq (an accurate high-throughput single-base method) and Nm-VAQ (a site-specific quantification tool). We identified thousands of new Nm sites on mRNA of human and mouse cell lines, in which 68 of 84 selected sites were further validated to be 2'-O-methylated more than 1%. Unlike rRNA, the methylated ratios of most validated mRNA Nm sites were lower than 30%. In addition, mRNA 2'-O-methylation was dynamic-changing according to the circumstance, which was presented with MHV infection. Furthermore, Nm sites of lung surgery samples revealed commonness of lung cancer pathogenesis, providing potential new diagnostic markers.

biochemistry↗

bioRxiv2019

Widespread positive selection for mRNA secondary structure at synonymous sites in domesticated yeast

mRNA secondary structure assumes a critical role in gene regulation, especially for translational efficiency. Previous studies have a growing appreciation of purifying selection for the conserved mRNA structure across lineages of different species. However, the effect of mRNA structure on positive evolution remains unclear. Here, we construct a large-scale dataset of single nucleotide polymorphisms (SNPs) at synonymous sites in the population of Saccharomyces cerevisiae, combined with the experimental assessment of mRNA structure, and perform empirical population genetics data analysis through unfolded site-frequency spectra. Our results suggest that functional mRNA stem drives faster evolution of increasing GC contents itself with the purpose of regulating translational speed, which is greatly influenced by length. At the synonymous site without codon usage bias, this kind of positive selection still exists. Furthermore, mRNA secondary structure is subject to positive selection widespread among the yeast genome, particularly related to mitochondria activities, which is possibly aimed to achieve a balance between cellular respiration and alcoholic fermentation precisely at a non-protein level. It is conducive to the adaption of the dramatic environment alterations from wild to man-made environments during the domestication.

evolutionary biology↗

bioRxiv2019

The Telomerase Reverse Transcriptase (TERT) and p53 Regulate Mammalian PNS and CNS Axon Regeneration downstream of c-Myc

Although several genes have been identified to promote axon regeneration in the central nervous system, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using sensory axon and optic nerve regeneration as model systems, we revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provided strong evidence that TERT and p53 acted downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells (RGCs) was sufficient to promote sensory axon and optic never regeneration, respectively. The study revealed a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.

neuroscience↗