PLM-ARG: antibiotic resistance gene identification using a pretrained protein language model.

MOTIVATION: Antibiotic resistance presents a formidable global challenge to public health and the environment. While considerable endeavors have been dedicated to identify antibiotic resistance genes (ARGs) for assessing the threat of antibiotic resistance, recent extensive investigations using metagenomic and metatranscriptomic approaches have unveiled a noteworthy concern. A significant fraction of proteins defies annotation through conventional sequence similarity-based methods, an issue that extends to ARGs, potentially leading to their under-recognition due to dissimilarities at the sequence level. RESULTS: Herein, we proposed an Artificial Intelligence-powered ARG identification framework using a pretrained large protein language model, enabling ARG identification and resistance category classification simultaneously. The proposed PLM-ARG was developed based on the most comprehensive ARG and related resistance category information (>28K ARGs and associated 29 resistance categories), yielding Matthew's correlation coefficients (MCCs) of 0.983 ± 0.001 by using a 5-fold cross-validation strategy. Furthermore, the PLM-ARG model was verified using an independent validation set and achieved an MCC of 0.838, outperforming other publicly available ARG prediction tools with an improvement range of 51.8%-107.9%. Moreover, the utility of the proposed PLM-ARG model was demonstrated by annotating resistance in the UniProt database and evaluating the impact of ARGs on the Earth's environmental microbiota. AVAILABILITY AND IMPLEMENTATION: PLM-ARG is available for academic purposes at https://github.com/Junwu302/PLM-ARG, and a user-friendly webserver (http://www.unimd.org/PLM-ARG) is also provided.

MagMD: Database summarizing the metabolic action of gut microbiota to drugs.

An increasing number of studies have reported that microbiome can affect drug response by altering pharmacokinetics and pharmacodynamics of formation of toxic metabolites. With the development of metagenomic sequencing, gut microbial composition as well as the metabolic function are drawing more and more attention for the patient stratification. The established microbiota databases provide useful information about the gut microbe-drug interactions. However, these databases generally lacked the detailed effects on substance and the metabolites, which are helpful in elucidating the mechanisms underlying drug biotransformation and personalized medicine. To address these issues, in this study, we developed Metabolic action of gut Microbiota to Drugs (MagMD), a database and a web-service covering 32, 678 records of interactions between 2,146 gut microbes, 36 enzymes and 219 substrates (mainly drugs). The detailed annotations for each entry, including the taxonomic level of microbes, the molecular form and PubChem ID of drugs from PubChem Compound Database, types of microbial secreted enzymes and the original reference links can also be accessed from the web service. Availability and implementation: MagMD is a publicly available resource, constantly updated. It has an intuitive web interface and can be freely accessed at http://www.unimd.org/magmd.

Comparative Transcriptome Analysis of Litopenaeus vannamei Reveals That Triosephosphate Isomerase-Like Genes Play an Important Role During Decapod Iridescent Virus 1 Infection.

Decapod iridescent virus 1 (DIV1) results in severe economic losses in shrimp aquaculture. However, little is known about the physiological effect of DIV1 infection on the host. In this study, we found that the lethal dose 50 of DIV1-infected Litopenaeus vannamei after 48, 72, 96, and 156 h were 4.86 × 106, 5.07 × 105, 2.13 × 105, and 2.38 × 104 copies/µg DNA, respectively. In order to investigate the mechanisms of DIV1 infection, a comparative transcriptome analysis of hemocytes from L. vannamei, infected or not with DIV1, was conducted. The BUSCO analysis showed that the transcriptome was with high completeness (complete single-copy BUSCOs: 57.3%, complete duplicated BUSCOs: 41.1%, fragmentation: 0.8%, missing: 0.8%). A total of 168,854 unigenes were assembled, with an average length of 601 bp. Based on homology searches, Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and cluster of orthologous groups of proteins (KOG) analysis, 62,270 (36.88%) unigenes were annotated. Among them, 1,112 differentially expressed genes (DEGs) were identified, of which 889 genes were up-regulated and 223 genes were down-regulated after DIV1 infection. These genes were mainly annotated to the major metabolic processes such as fructose and mannose metabolism, carbon metabolism, and inositol phosphate metabolism. Among these metabolic pathways, the triosephosphate isomerase (TPI) family was the most eye-catching DEG as it participates in several metabolic processes. Three types of TPI, LvTPI-like, LvTPI-Blike, and LvTPI-Blike1, were obtained for gene silencing by RNA interference. The results showed that LvTPI-like and LvTPI-Blike1 silencing caused a high mortality rate among L. vannamei. However, LvTPI-like and LvTPI-Blike silencing reduced DIV1 replication in DIV1-infected L. vannamei. All the results indicated that TPI-like genes play an important role during DIV1 infection, which provides valuable insight into the infection mechanism of DIV1 in shrimp and may aid in preventing viral diseases in shrimp culture.

Research into the hemocyte immune response of Fenneropenaeus merguiensis under decapod iridescent virus 1 (DIV1) challenge using transcriptome analysis.

The banana shrimp (Fenneropenaeus merguiensis) is a common cultural species worldwide. With the development of the shrimp farming industry, increasing number of diseases have emerged and cause huge impacts. Decapod iridescent virus 1 (DIV1) is a new virus of the family Iridoviridae isolated in China that causes very high mortality in shrimp. In this study, DIV1 and PBS were injected into two groups of shrimp, and hemocytes were collected for comparative transcriptomic analysis. We confirmed that F. merguiensis was the new host of DIV1 by nested PCR. A total of 100,759 unigenes were assembled from the control group and the DIV1 infected group, with an average length of 733.06 bp and N50 of 1136 bp. Significant hits were found in 21,465 unigenes compared to known sequences in major databases including COG (33.30%), GO (42.17%), KEGG (46.76%), KOG (61.37%), Pfam (66.90%), Swissprot (54.21%) and Nr (93.86%). A total of 1003 differentially expressed genes (DEGs) were identified, including 929 up-regulated genes and 74 down-regulated genes. Several known immune-related genes, including caspase, C-type lectin, Wnt5 and integrin, were among the differentially expressed transcripts. A total of 14,459 simple sequence repeats, including 8128 monomers, 3276 dimers, 1693 trimers, 150 quadmers, 4 pentamers and 16 hexamers, were found in the transcriptomic dataset. Our study is the first comprehensive investigation of the transcriptomic response to DIV1 infection in F. merguiensis. Collectively, these results not only provide valuable information for characterizing the immune mechanisms of the shrimp responses to DIV1 infection, they open new ways for the study of the molecular mechanisms of DIV1 infection in F. merguiensis.

Dietary supplementation with polypeptides improved growth performance, antibacterial immune and intestinal microbiota structure of Litopenaeus vannamei.

Antibacterial peptides (AMPs) are expected to replace some or all of the antibiotics and become a new feed additive. However, the high production cost and unclear mechanism limited the application of AMPs. In this research, the effects of a commercial polypeptide (Polypeptide S100) whose main components are AMPs on the growth, antibacterial immune and intestinal microbial of Litopenaeus vannamei were study. L. vannamei (initial weight of 0.16 ±â€¯0.03 g) were fed for 123 days with basal diet added Polypeptide S100 at two levels each (0.5% and 1%) as experimental groups, and a basal diet as control. Dietary inclusion of Polypeptide S100 at 1% level significantly increased the weight gain (WG) and specific growth rate (SGR) of L. vannamei. The survival rates of L. vannamei in 0.5% and 1% Polypeptide S100 groups were significantly higher than the control when infected by Vibrio harveyi but not Vibrio parahaemolyticus. The activities of total superoxide dismutase (T-SOD) and lysozyme (LZM) in the two experimental groups were all significantly higher than the control. Differently, the activities of amylase (AMS) and lipase (LPS) were significantly higher in 0.5% Polypeptide S100 group but lower in 1.0% Polypeptide S100 group. Illumina MiSeq high-throughput sequencing showed that the dominant phyla in the intestine of L. vannamei were Proteobacteria, followed by Actinobacteria, Bacteroidetes, Chloroflexi, Cyanobacteria, Fusobacteria and Tenericutes, and the abundance of predominant phyla Cyanobacteria were upregulated significantly in the experimental groups. At the family level, significant increase was observed in Pseudomonadaceae and Xanthomonadaceae but decrease in Vibrionaceae in the 1.0% Polypeptide S100 group. The abundance of predominant genus Photobacterium were obviously downregulated in the two experimental groups. Unlikely, the abundance of Pseudomonas and Stenotrophomonas were distinctly increased in the 1.0% Polypeptide S100 group but not significantly different from the control in 0.5% Polypeptide S100 group. All these results suggested that Polypeptide S100 could improve the growth performance, antibacterial immune and intestinal microbiota structure of L. vannamei.

[The characteristics of microstructure and chemical compositions of K-feldspar, sphene and zircon with zoning structure].

K-feldspar, sphene and zircon in quartz monzonite from Shahewan, south Qinling, showing strong zoning structure. Characteristics of microstructure and chemical compositions of K-feldspar, sphene and zircon with zoning structure were investigated using advanced instruments of electron probe micro analyses equipped with wavelength dispersive spectrometer (EPM-WDS), scanning electron microscopy with energy dispersive spectrometer (SEM-EDS) and laser ablation--inductively coupled plasma--mass spectrometry (LA-ICP-MS). Our study suggests that K+ could be substituted by small amounts of Na+, Ca2+, Ba2+, Fe2+ and Ce3+. Ca2+ in sphene could be replaced by V3+, Ce3+, Ba2+ and Ti4+ could be substituted by both Fe2+ and Al3+. Zircon contains trace elements like Fe, Th, U, Nb, Ta, Y, Hf, Yb and Pb. Concentration of Si, Al, K, Ca, Na, Mg and Ba in K-feldspar ranked from high to low, among which the contents of K and Na are negatively correlated, the lighter part of BSE images featuring K-feldspar is attributed to comparably higher Ba content, additionally, Si and K contents are elevated while Na content decreased rimward. Ca, Si, Ti, Ba, V, Ce, Al and Fe concentration listed downward, among which higher iron content corresponds to brighter portion of BSE images. Element concentration of zircon could be ranked from high to low as Zr, Si, Nd, Ce, Hf, U, Pb and Th, in which Hf and Zr exhibit negatively correlated. Zr concentration increased while Hf, U and Th concentration decreased from core to rim.