Biology subjects

peng, z.

Publications and source records attributed to peng, z..

3 recordsLinked to original sources

bioRxiv2023

AutoHiC: a deep-learning method for automatic and accurate chromosome-level genome assembly

An accurate genome at the chromosome level is the key to unraveling the mysteries of gene function and unlocking the mechanisms of disease. Irrespective of the sequencing methodology adopted, Hi-C aided scaffolding serves as a principal avenue for generating genome assemblies at the chromosomal level. However, the results of such scaffolding are often flawed and require extensive manual refinement. In this paper, we introduce AutoHiC, an innovative deep learning-based tool designed to identify and rectify genome assembly errors. Diverging from conventional approaches, AutoHiC harnesses the power of high-dimensional Hi-C data to enhance genome continuity and accuracy through a fully automated workflow and iterative error correction mechanism. AutoHiC was trained on Hi-C data from more than 300 species (approximately five hundred thousand interaction maps) in DNA Zoo and NCBI. Its confusion matrix results show that the average error detection accuracy is over 90%, and the area under the precision-recall curve is close to 1, making it a powerful error detection capability. The benchmarking results demonstrate AutoHiCs ability to substantially enhance genome continuity and significantly reduce error rates, providing a more reliable foundation for genomics research. Furthermore, AutoHiC generates comprehensive result reports, offering users insights into the assembly process and outcomes. In summary, AutoHiC represents a breakthrough in automated error detection and correction for genome assembly, effectively promoting more accurate and comprehensive genome assemblies.

bioinformatics↗

bioRxiv2023

Development of a xylose-inducible promoter and riboswitch combination system for manipulating gene expression in Fusobacterium nucleatum

Inducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls in Fusobacterium nucleatum by integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in an ftsX mutant strain, unveiling a dose-dependent manner in FtsX production. Without inducers, cells form long filaments, while increasing FtsX levels by increasing inducers concentrations led to a gradual reduction in cell length until normal morphology was restored. Crucially, this system facilitated essential gene investigation, identifying the signal peptidase lepB gene as vital for F. nucleatum. LepBs essentiality stems from depletion, affecting outer membrane biogenesis and cell division. This novel hybrid system holds the potential for advancing research on essential genes and accurate gene regulation in F. nucleatum.

microbiology↗

bioRxiv2023

Amino acid transporter SLC7A5 regulates Paneth cell function to affect the intestinal inflammatory response

The intestine is critical for not only processing and resorbing nutrients but also protecting the organism from the environment. These functions are mainly carried out by the epithelium, which is constantly being self-renewed. Many genes and pathways can influence intestinal epithelial cell proliferation. Among them is mTORC1, whose activation increases cell proliferation. Here, we report the first intestinal epithelial cell-specific knockout ({Delta}IEC) of an amino acid transporter capable of activating mTORC1. We show that the transporter, SLC7A5, is highly expressed in mouse intestinal crypt and Slc7a5{Delta}IEC reduces mTORC1 signaling. Surprisingly, Slc7a5{Delta}IEC mice have increased cell proliferation but reduced secretory cells, particularly mature Paneth cells. scRNA-seq and electron microscopic analyses revealed dedifferentiation of Paneth cells in Slc7a5{Delta}IEC mice, leading to markedly reduced secretory granules with little effect on Paneth cell number. We further show that Slc7a5{Delta}IEC mice are prone to experimental colitis. Thus, SLC7A5 regulates secretory cell differentiation to affect stem cell niche and/or inflammatory response to regulate cell proliferation.

immunology↗