Biology subjects

She, J.

Publications and source records attributed to She, J..

10 recordsLinked to original sources

bioRxiv2026

CnidoSite: A Multi-Omics Database for Cnidarians

The phylum Cnidaria, encompassing reef-building corals, sea anemones, hydroids, and jellyfish, includes both ecological keystones of the marine biosphere and indispensable models for reconstructing early animal evolution. However, escalating ocean warming, recurrent mass coral bleaching events, and intensifying jellyfish blooms have underscored the urgent need to dissect the molecular underpinnings of cnidarian thermal tolerance, symbiosis, and environmental adaptation. Progress in cnidarian research is hindered by the lack of centralized, high-quality multi-omics resources. To address this, we present CnidoSite (https://CnidoSite.org), a comprehensive, analysis-ready multi-omics platform dedicated to Cnidaria. Spanning 327 species across 120 families, 23 orders, and 7 classes, it integrates 147 full-annotated genomes, 15,642 bulk transcriptomes, 50 single-cell datasets, 46 proteomes, 723 epigenomes, 1,650 metagenomic samples, and 180,652 phenotype records. Complemented by advanced toolkits for multidimensional functional and comparative analyses, CnidoSite provides extensive functional genomic resources, including genome assemblies, phylogenies, fossil entries, functional annotations, BUSCO assessments, and mitochondrial annotations. Key features include 29 co-expression networks with cross-tissue visualization and single-cell atlases to map developmental trajectories and stress responses. In summary, CnidoSite serves as a centralized platform that bridges cnidarian biology, marine conservation, and evolutionary genomics to investigate coral bleaching, symbiosis breakdown, jellyfish blooms, and the mechanisms driving environmental adaptation.

bioinformatics↗

bioRxiv2025

Comprehensive benchmarking with guidelines for analyzing transposable element-derived RNA expression

Transposable element-derived RNAs (teRNAs) have been recognized with accelerating fundamental or pathogenic roles, especially in human. Despite the rapid development of computational methods, the best practice for accurate identification and quantification of teRNAs are currently lacking owing to the difficulties of evaluation. Here we present benchmarking of 16 representative tools with 120 simulated datasets and 60 real-world paired datasets (comprising both long- and short-read data), by evaluating the performance of teRNA identification or quantification across family-, unit-, exon-, and transcript-level. Our findings demonstrate not only the exon-level as a trade-off between accuracy and resolution for teRNA analysis, but also the level-dependent strengths and weaknesses of evaluated methods. To refine our benchmarking results, we present decision-tree-style guidelines and develop an integrated best-practice pipeline, serving as the basis for future functional researches. In addition, our evaluation framework also provides a gold standard for developing and benchmarking better computational tools in the field.

bioinformatics↗

bioRxiv2025

Transposable elements drive species-specific and tissue-specific transcriptomes in human development

BackgroundTransposable elements (TEs) are an abundant and crucial regulatory resource in the human genome. Serving as alternative promoters, TEs can be reactivated and produce TE-initiated transcripts, which play importance roles in early development and differentiated tissues. However, the prevalence and function of TE-initiated transcription in human development are poorly characterized. ResultsWe identified 12,918 TE-initiated transcripts across 40 human body sites and embryonic stem cells. Among TE-initiated transcripts, 80% were activated in a tissue-specific manner. TEs with tissue-specific transcription factor binding motifs were enriched in particular tissues. Additionally, approximately half of TE-derived TSSs were primates-specific. Notably, 375 primates-specific TE-derived TSSs were found to create novel tissue-specific gene expression patterns during evolution. ConclusionsOur results characterize the global profile of TE-initiated transcription and enhance our understanding of TE contribution to the primate-specific gene regulatory networks in human development.

bioinformatics↗

bioRxiv2025

TEITbase: a database for transposable element (TE)-initiated transcripts in human cancers

Transposable elements (TEs) are abundant and play a crucial regulatory role in the human genome. Functioning as alternative promoters, TEs can be reactivated to produce TE-initiated transcripts. In cancer, TE-initiated transcription may upregulate oncogene expression and generate novel tumor-specific antigens, which could serve as potential targets for immunotherapy. However, there remains a lack of comprehensive databases that systematically investigate TE-initiated transcription in cancer. To address this gap, we developed a deep learning-based method and identified 38,995 TE-initiated transcripts across 33 cancer types from The Cancer Genome Atlas. Among these, 6,203 were tumor-specific expressed and strongly associated with the tumorigenesis. Using these annotations, we created TEITbase (http://teitbase.medbioinfo.org/), a user-friendly database that provides researchers with tools to conduct various downstream analyses and investigations for TE-initiated transcripts, including 546 novel onco-exaptation events. The establishment of TEITbase provides new insights into transcriptional reprogramming in cancers and enables further investigation into the potential roles of TE-initiated transcripts in cancer diagnostics and therapeutic strategies.

bioinformatics↗

bioRxiv2025

Obesity Increases Atherosclerosis Susceptibility via Inter-tissue miR-30e-SLC7A11 Axis

BackgroundWith obesity as a risk factor for atherosclerotic disease, recent research suggests that adipose tissue in obese animal models and humans can generate endocrine-like molecules that affect arterial health later on. Previous studies showed that microRNA-30e (miR-30e) level is elevated in atherosclerosis and solute carrier family 7 member 11 (SLC7A11), a cystine/glutamate transporter, is involved in atherogenesis. However, whether an endocrine-like link between the adipose-derived miR-30e-5p and SLC7A11 in the vascular endothelium can lead to obesity-caused atherosclerosis is unknown. MethodsMiRNA data mining and RT-PCR validations were used to demonstrate the positive association among serum level of miR-30e-5p, obesity, and coronary arterial disease in human patients. Transcriptomics (RNA-seq and single-nucleus RNA-seq), metabolomics, and in silico analysis were used to establish a miR-30e-5p-SLC7A11 regulation of central carbon metabolism, mitochondrial and endothelial cell (EC) function. Mouse models with EC-specific Slc7a11 knockout (EC-Slc7a11-/-) and gain or loss of function of miR-30e-5p were used to elucidate the detrimental role of this endocrine-like axis in obesity-related atherosclerosis. ResultsThe level of adipocyte-derived miR-30e-5p was significantly upregulated in obese humans with coronary artery disease and obese and atherosclerotic mice. Via serum exosomes, the adipocyte-generated miR-30e-5p targeted SLC7A11 mRNA in vascular ECs. SLC7A11 deficiency due to miR-30e-5p targeting dysregulated glutamate/cystine metabolism increased glycolysis, reduced oxidative phosphorylation, and impaired mitochondrial function. The EC dysfunction could be rectified by SLC7A11 overexpression or miR-30e-5p antagonism. Exogenously delivered miR-30e-5p phenocopied the increased atherosclerosis in EC-Slc7a11-/- mice. In contrast, miR-30e-5p antagomir treatment reduced atherosclerosis in Apoe-/- and ob/ob mice. ConclusionOur multi-omics approaches demonstrates that the adipose-derived miR-30e-5p downregulated SLC7A11 mRNA in ECs via tissue crosstalk. The resulting EC dysfunction led to obesity-related atherosclerosis in mice. These findings underscore a causality between obesity and atherosclerosis in the context of cardiovascular-kidney-metabolic syndrome.

molecular biology↗

bioRxiv2023

Epigenetic regulation of p63 blocks squamous-to-neuroendocrine transdifferentiation in esophageal development and malignancy

While cell fate determination and maintenance are important in establishing and preserving tissue identity and function during development, aberrant cell fate transition leads to cancer cell heterogeneity and resistance to treatment. Here, we report an unexpected role for the transcription factor p63 (Trp63/TP63) in the fate choice of squamous versus neuroendocrine lineage in esophageal development and malignancy. Deletion of p63 results in extensive neuroendocrine differentiation in the developing mouse esophagus and esophageal progenitors derived from human embryonic stem cells. In human esophageal neuroendocrine carcinoma (eNEC) cells, p63 is transcriptionally silenced by EZH2-mediated H3K27 trimethylation (H3K27me3). Upregulation of the major p63 isoform {Delta}Np63, through either ectopic expression or EZH2 inhibition, promotes squamous transdifferentiation of eNEC cells. Together these findings uncover p63 as a rheostat in coordinating the transition between squamous and neuroendocrine cell fates during esophageal development and tumor progression.

cell biology↗

bioRxiv2022

ccnWheat: A Database for Comparing Co-expression Networks Analysis of Allohexaploid Wheat and Its Progenitors

Genetic and epigenetic changes after polyploidization events could result in variable gene expression and modified regulatory networks. Here, using large-scale transcriptome data, we constructed co-expression networks for diploid, tetraploid, and hexaploid wheat species, and built a platform for comparing co-expression networks of allohexaploid wheat and its progenitors, named ccnWheat. ccnWheat is a platform for searching and comparing specific functional co-expression networks, as well as identifying the related functions of the genes clustered therein. Functional annotations like pathway, gene family, protein-protein interactions, microRNA (miRNA), and several lines of epigenome data are integrated in this platform, and Gene Ontology (GO) annotation, gene set enrichment analysis (GSEA), motif identification, and other useful tools are also included. Using ccnWheat, we found that the network of WHEAT ABERRANT PANICLE ORGANIZATION 1 (WAPO1) has more co-expressed genes related to spike development in hexaploid wheat than its progenitors. We also found a novel motif of CArG specifically in the promoter region of WAPO-A1, suggesting that neofunctionalization of the WAPO-A1 gene affects spikelet development in hexaploid wheat. ccnWheat is useful for investigating co-expression networks and conducting other associated analyses, and thus facilitates comparative and functional genomic studies in wheat. ccnWheat is freely available at http://bioinformatics.cau.edu.cn/ccnWheat.

bioinformatics↗

bioRxiv2020

DEBKS: A Tool to Detect Differentially Expressed Circular RNA

Circular RNAs (circRNAs) are involved in various biological processes and in disease pathogenesis. However, only a small number of functional circRNAs have been identified among hundreds of thousands of circRNA species, partly because most current methods are based on circular junction counts and overlook the fact that circRNA is formed from the host gene by back-splicing (BS). To distinguish between expression originating from BS and that from the host gene, we present DEBKS, a software program to streamline the discovery of differential BS between two rRNA-depleted RNA sequencing (RNA-seq) sample groups. By applying real and simulated data and employing RT-qPCR for validation, we demonstrate that DEBKS is efficient and accurate in detecting circRNAs with differential BS events between paired and unpaired sample groups. DEBKS is available at https://github.com/yangence/DEBKS as open-source software.

bioinformatics↗

bioRxiv2020

Structural insights into the Ca 2+-dependent gating of the human mitochondrial calcium uniporter

Mitochondrial Ca2+ uptake plays an important role in cellular physiology such as modulating ATP production, regulating cytoplasmic Ca2+ dynamics, and triggering cell death, and is mediated by the mitochondrial calcium uniporter, a highly selective calcium channel localized to the inner mitochondrial membrane. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca2+ dependent manner. Here we present the EM structures of the human mitochondrial calcium uniporter holocomplex (uniplex) in the presence and absence of Ca2+, revealing distinct Ca2+ dependent assembly of the uniplex. In the presence of Ca2+, MICU1 and MICU2 form a heterotetramer of MICU1-(MICU2)2-MICU1 and bridge the dimeric form of the MCU-EMRE subcomplex through electrostatic interactions between MICU1 and EMRE, leaving the MCU channel pore unblocked. In the absence of Ca2+, multiple uniplex assemblies are observed but is predominantly occupied by the MICU1 subunit from a MICU1-MICU2 heterodimer blocking the MCU channel pore. Our structural observations suggest that Ca2+ changes the dimerization interaction between MICU1 and MICU2, which in turn determines how the MICU1-MICU2 subcomplex interacts with the MCU-EMRE channel and, consequently, changes the distribution of the uniplex assemblies between the blocked and unblocked states.View Full Text

biochemistry↗

bioRxiv2020

Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

Gastric cancer (GC) is a heterogeneous disease of diverse genetic, genomic, and epigenetic alterations. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate GC heterogeneity, we developed an Integrative Sequential Causality Test (ISCT) to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts containing methylation, CNV and transcriptomic data, 11 common methylation-driven key regulators (ADHFE1, CDO1, CRYAB, FSTL1, GPT, PKP3, PTPRCAP, RAB25, RHOH, SFN, and SORD) were identified. Based on these 11 genes, gastric tumors were clustered into 3 clusters which were associated with known molecular subtypes, Lauren classification, tumor stage, and patient survival, suggesting significance of the methylation-driven key regulators in molecular and histological heterogeneity of GC. We further showed that chemotherapy benefit was different in the 3 GC clusters and varied depending on the tumor stage. Both immune/stromal proportions in TME and tumor cell genomic variations contributed to expression variations of the 11 methylation-driven key regulators and to the GC heterogeneity.

genomics↗