Biology subjects

Xin, C.

Publications and source records attributed to Xin, C..

6 recordsLinked to original sources

bioRxiv2025

MF-ProtDisMap: protein real-valued distance prediction with fusion of sequence and coevolutionary features

The precise estimation of protein inter-residue distances is essential for high-accuracy protein structure modeling. Currently, the prediction methods are predominantly based on MSA-derived coevolutionary features or language model-based sequence features. To effectively leverage the strengths of both methods, this study developed MF-ProtDisMap (Multi-Feature Protein Distance Map), an integrative framework that effectively combines both feature types to achieve superior real-valued distance prediction. Briefly, MSA Transformer is employed to extract the coevolutionary features from protein multiple sequence alignments, whereas ESM2 is used to capture long-range interactions and sequence-level features. To reduce the computational cost while maximumly represent fused feature information, we implement group pooling for feature dimensionality reduction and introduce Diff-former--a novel module combining a diffusion model with a triangular attention mechanism to enhance representation learning. MF-ProtDisMap achieved a MAE of 2.20 [A] and an RMSE of 3.40 [A] in the protein real-valued distance prediction task. The predicted distances can be converted into contact results, achieving ROC and PR values of 84.56% and 81.01%, respectively. These results demonstrate that MF-ProtDisMap outperforms state-of-the-art real-valued protein distance methods.

bioinformatics↗

bioRxiv2025

Prevalence of Campylobacter and non-typhoidal Salmonella along broiler chicken production and distribution networks, Vietnam

Campylobacter and non-typhoidal Salmonella (NTS) are among the most common foodborne pathogens found in chickens at any production stage and cause gastroenteritis in humans. This study aimed to estimate the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in broiler production and distribution networks (PDN) using a Bayesian approach. A cross-sectional study was conducted in four provinces in northern Vietnam between March 2021 and March 2022. A total of 102 sites, including live bird markets, slaughter facilities (slaughterhouses and slaughter points), and their supplying farms, were randomly selected for sampling. Cecal and environmental samples were cultured for isolation of Campylobacter and NTS, with serotypes of NTS determined by targeted analysis of whole genome sequences. Bayesian models were developed to estimate the prevalence of Campylobacter at two levels (bird-level and site-level) and NTS at site-level. The selected best-fitted models indicated that C. jejuni prevalence was primarily influenced by site type, while C. coli was affected by both province and site types. For NTS, only site type was included. The highest overall prevalence of infected broilers was estimated on farms for C. coli (26.2% [95% High Density Interval (HDI): 19.0-36.0%]) and C. jejuni (19.9% [95%HDI 13.0-27.0%]). Slaughter points (97.6% [95%HDI 63.3-99.9%]) and wholesale markets (91.7% [95%HDI 28.2-99.9%]) had the highest probability of C. coli and C. jejuni contamination, respectively, but retail markets had the highest proportion of infected broilers at contaminated sites. NTS contamination was more frequent in markets and slaughter facilities (42.8% [95%HDI 30.8-57.1%]) than on farms (18.6% [95%HDI 9.5-30.1%]). Among 16 detected NTS serotypes, S. Infantis and S. Kentucky were the most common. These findings highlight the widespread contamination of broiler PDNs with Campylobacter and NTS in northern Vietnam, emphasizing the need for enhanced surveillance and control measures in PDNs to mitigate the risk of foodborne transmission. Author SummaryCampylobacter spp. and non-typhoidal Salmonella (NTS) are enteric pathogens that are key global pathogens causing diarrheal diseases. The Campylobacter species that are most frequently responsible for human diseases (campylobacteriosis) are Campylobacter jejuni (C. jejuni) and Campylobacter coli (C. coli). The severity of the salmonellosis depends on host factors and the serotype of NTS. Poultry and poultry products are recognized as major sources of NTS and Campylobacter infections in humans. In Vietnam, these pathogens have been detected in the broiler production and distribution networks (PDN). Factors that may increase the risk of transmission of those pathogens include low biosecurity practices, inadequate waste management, and high farm density. In this work, we estimated the prevalence of Campylobacter spp. (C. coli and C. jejuni) and NTS in PDN markets and slaughterhouses and farms supplying these facilities in four provinces in northern Vietnam. We estimated a high prevalence of Campylobacter contamination in slaughter points and wholesale markets and higher NTS contamination in slaughter facilities and markets than in farms. S. Infantis was one of the most frequently identified serovars. However, it was not reported as being frequently detected in humans in Vietnam. Therefore, serovar may vary depending on the source and region of contamination. Our results help us look at levels of infection/contamination with Campylobacter and NTS in the broiler PDNs, thus informing stakeholders to prevent and control campylobacteriosis and salmonellosis.

microbiology↗

bioRxiv2024

Clair3-RNA: A deep learning-based small variant caller for long-read RNA sequencing data

Variant calling using long-read RNA sequencing (lrRNA-seq) can be applied to diverse tasks, such as capturing full-length isoforms and gene expression profiling. It poses challenges, however, due to higher error rates than DNA data, the complexities of transcript diversity, RNA editing events, etc. In this paper, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data. Clair3-RNA leverages the strengths of the Clair series pipelines and incorporates several techniques optimized for lrRNA-seq data, such as uneven coverage normalization, refinement of training materials, editing site discovery, and the incorporation of phasing haplotype to enhance variant-calling performance. Clair3-RNA is available for various platforms, including PacBio and ONT complementary DNA sequencing (cDNA), and ONT direct RNA sequencing (dRNA). Our results demonstrated that Clair3-RNA achieved a [~]91% SNP F1-score on the ONT platform using the latest ONT SQK-RNA004 kit (dRNA004) and a [~]92% SNP F1-score in PacBio Iso-Seq and MAS-Seq for variants supported by at least four reads. The performance reached a [~]95% and [~]96% F1-score for ONT and PacBio, respectively, with at least ten supporting reads and disregarding the zygosity. With read phased, the performance reached [~]97% for ONT and [~]98% for PacBio. Extensive evaluation of various GIAB samples demonstrated that Clair3-RNA consistently outperformed existing callers and is capable of distinguishing RNA high-quality editing sites from variants accurately. Clair3-RNA is open-source and available at (https://github.com/HKU-BAL/Clair3-RNA).

bioinformatics↗

bioRxiv2023

Genome editing induces the transfer of mitochondrial DNA into the nuclear genome

Mitochondria serve as the cellular powerhouse, and their distinct DNA makes them a prospective target for gene editing to treat genetic disorders. However, the impact of genome editing on mitochondrial DNA (mtDNA) stability remains a mystery. Our study reveals previously unknown risks of genome editing that both nuclear and mitochondrial editing cause broad transfer of mitochondrial DNA segments into the nuclear genome in various cell types including human cell lines, primary T cells, retinal cells, and mouse embryos. Furthermore, drug-induced mitochondrial stresses and mtDNA breaks exacerbate this transfer of mtDNA into the nuclear genome. Notably, we observe that the newly developed mitochondrial base editor DdCBE can also cause widespread mtDNA integrations. However, we provide a practical solution to suppress the transfer of mtDNA by co-expressing TREX1 or TREX2 exonucleases during DdCBE editing. These findings also shed light on the origins of mitochondrial-nuclear DNA segments.

genomics↗

bioRxiv2021

MS2 RNA aptamer enhances prime editing in rice

Prime editing is a universal and very promising precise genome editing technology. However, optimization of prime editor (PE) from different aspects remains vital for its use as a routine tool in plant basic research and crop molecular breeding. In this report, we tested MS2-based prime editor (MS2PE). We fused the M-MLV reverse transcriptase (RT) gene variant to the MS2 RNA binding protein gene, MCP, and allowed the MCP-RT fusion gene to co-express with the SpCas9 nickase gene, SpCas9H840A, and various engineered pegRNAs harboring MS2 RNA (MS2pegR). Compared with control PEs, MS2PEs significantly enhanced editing efficiency at four of six targets in rice protoplasts, and achieved 1.2[~]10.1-fold increase in editing efficiency at five of six targets in transgenic rice lines. Furthermore, we tested total 22 different MS2pegR scaffolds, 3 RT variants or genes, 2 MCP variants, and various combinations of the Cas9 nickase, RT, and MCP modules. Our results demonstrated an alternative strategy for enhancing prime editing.

molecular biology↗

bioRxiv2021

Global detection of DNA repair outcomes induced by CRISPR-Cas9

CRISPR-Cas9 generates double-stranded DNA breaks (DSBs) to activate cellular DNA repair pathways for genome editing. The repair of DSBs leads to small insertions or deletions (indels) and other complex byproducts, including large deletions and chromosomal translocations. Indels are well understood to disrupt target genes, while the other deleterious byproducts remain elusive. We developed a new in silico analysis pipeline for the previously described primer-extension-mediated sequencing assay to comprehensively characterize CRISPR-Cas9-induced DSB repair outcomes in human or mouse cells. We identified tremendous deleterious DSB repair byproducts of CRISPR-Cas9 editing, including large deletions, plasmid integrations, and chromosomal translocations. We further elucidated the important roles of microhomology, chromosomal interaction, recurrent DSBs, and DSB repair pathways in the generation of these byproducts. Our findings provide an extra dimension for genome editing safety besides off-targets. And caution should be exercised to avoid not only off-target damages but also deleterious DSB repair byproducts during genome editing.

genomics↗