Biology subjects

Ru, J.

Publications and source records attributed to Ru, J..

7 recordsLinked to original sources

bioRxiv2024

Metagenomic analyses of single phages and phage cocktails show instances of contamination with temperate phages and bacterial DNA

Increasing antibiotic resistance has led to renewed attention being paid to bacteriophage therapy. Commercial phage cocktails are available but often their contents of the phages are not well defined. Some metagenomic studies have been done to retrospectively characterise these cocktails, but little is known about the replication cycle of the included phages, or about the possible bacterial DNA contamination. In this study, published metagenomic sequences were reanalysed using recent advances in viromics tools. Signs of temperate phage contigs were found in all cocktail metagenomes, as well as host DNA, which could poses a risk as it may lead to horizontal gene transfer of virulence factors to commensals and pathogens. This suggests the need to implement further quality measures before using phage cocktails therapeutically.

microbiology↗

bioRxiv2022

Replidec - Use naive Bayes classifier to identify virus lifecycle from metagenomics data

MotivationViruses are the most abundant biological entities on earth. The majority of these entities are bacterial viruses or phages which specifically infect bacteria. Phages can use different replication strategies to invade their hosts including lytic, lysogenic, chronic cycle and pseudolysogeny. While the determination of the replication strategy used by phages is important to explore the phage-bacteria relationships in different ecosystems there are not many tools that can predict this in metagenomic data. In addition, most of the tools available can only predict lytic and lysogenic cycles. To address this issue, we have developed a new software called Replidec to identify three most common phage replication cycles (virulent, temperate, chronic) in viral sequences. ResultsReplidec uses Naive Bayes classifier combined with alignment-based methods to improve the prediction accuracy in metagenomic data. We test Replidec on viral genomes with known replication cycle and simulated metagenomic sequences. Replidec perform relatively good both in isolated genomes (F1 score: 92.29% {+/-} 0.81; mcc: 89.14% {+/-} 1.22) and simulated metagenomic sequences(F1 score: 87.55% {+/-} 2.12; mcc: 88.23% {+/-} 2.55). Moreover, Replidec can also accurately predict the replication cycle in small viral fragments([~]3000bp). In conclusion, Replidec can achieve the best performance in simulated metagenomic data compared to most prediction softwares including BACPHLIP.

bioinformatics↗

bioRxiv2022

Altered virome structrue and function characterization in Helicobacter pylori-driven colorectal carcinogenesis and H. pylori eradication

The understanding of gut virome and its role in Helicobacter pylori-driven colorectal cancer (CRC), as well as the long-term impact of H. pylori eradication via antibiotic treatment on it could contribute to better understanding the mechanisms of the disruption of gut bacteriome homeostasis involved in H. pylori-driven colorectal carcinogenesis and antibiotic therapy for H. pylori eradication. In the dynamic analysis of viral genome shotgun metagenomic of samples from lower gastrointestinal tract of the Apc+/1638N and C57BL/6 mice with H. pylori infection and eradication, stable viral abundance and replacement of bursted unique viral contigs in infected and uninfected Apc+/1638N mice were observed. Temperate phages, which encoding comprehensive microbial functional genes and targeting various susceptible hosts, were expanded extremely prior to cancer exacerbation. In addition, short-term antibiotic exposure for H. pylori eradication was able to alter the gut virome and thrive the antibiotic resistance genes (ARGs) in the viral genome for at least 6 months. Collectively, these results point toward a potential role of the altered, but dynamically balanced gut virome, characterized by the expanded temperate phages, in contributing to the H. pylori-driven CRC, and indicate that viral genome may act as ARG reservoir for the antibiotic resistance of bacteria after the antibiotics therapy to H. pylori eradication.

microbiology↗

bioRxiv2022

DeepsmirUD: Precise prediction of regulatory effects on miRNA expression mediated by small molecular compounds using competing deep learning frameworks

Aberrant miRNA expression has pervasively been found to relate to a growing number of human diseases. Therefore, targeting miRNAs to regulate their expression levels has become an important therapy against diseases that stem from the dysfunction of oncogenic pathways regulated by the miRNAs. In recent years, small molecule compounds have demonstrated enormous potential as drugs to regulate miRNA expression (i.e., SM-miR). A clear understanding of the mechanism of action of small molecules on down- and up-regulating miRNA expression allows precise diagnosis and treatment of oncogenic pathways. However, outside of a slow and costly process of experimental determination, computational strategies to assist this in an ad hoc manner have still not been enabled. In this work, we develop, to the best of our knowledge, the first prediction tool, DeepsmirUD, to infer small molecule-mediated regulatory effects on miRNA expression. This method is powered by an ensemble of 12 cutting-edged deep learning frameworks and achieves state-of-the-art performance with AUC values of 0.840/0.969 and AUCPR values of 0.866/0.983 on two independent test datasets. With a complementarily constructed network inference approach based on similarity, we report a significantly improved accuracy of 0.813 in determining regulatory effects of nearly 650 SM-miR relations formed with either novel small molecules or novel miRNAs. By further integrating miRNA-cancer relations, we established a database of potentially pharmaceutical drugs to aid in understanding the drug mechanisms of action in diseases and to offer novel insight into drug repositioning. Taken together, our method shows great promise to assist and accelerate the therapeutic development of potential miRNA targets and small molecule drugs. Furthermore, we have employed DeepsmirUD to predict regulatory effects of a large number of high-confidence SM-miR relations curated from Psmir, which are publicly available through https://github.com/2003100127/deepsmirud and https://rujinlong.github.io/deepsmirud/ alongside the DeepsmirUD standalone package.

bioinformatics↗

bioRxiv2021

Tmem138, a photoreceptor connecting cilium (CC) protein, is required for rhodopsin transport across the cilium and outer segment (OS) biogenesis

Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as non-syndromic retinal degenerations. Despite extensive studies, protein trafficking across the photoreceptor CC is largely unknown. Here we genetically inactivated mouse Tmem138, a gene encoding a ciliary membrane protein localized to the ciliary TZ and linked to Joubert syndrome (JBTS). Germline deletion of Tmem138 abolished OS morphogenesis followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and, accordingly, the molecular compartments of the CC and axoneme of the mutant photoreceptors were altered despite ciliogenesis proceeding normally at the early stage of photoreceptor development. To gain further insights into Tmem138 function in OS biogenesis, we focused on trafficking of rhodopsin, the most abundant protein of the OS. Mislocalization of rhodopsin was readily observed as early as P5 in the mutant photoreceptors prior to growth of the OS. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing well-formed outer segment discs to disintegrate accompanied by mislocalization of rhodopsin in the cell body. Furthermore, Tmem138 interacted with rhodopsin, and two additional CC compartment proteins Ahi1 and Tmem231, which were both altered in the mutant photoreceptors. Taken together, these results suggest that Tmem138 has a distinct role in gating the transport of rhodopsin and likely other OS bound proteins through formation of CC transport complex(es).

cell biology↗

bioRxiv2020

Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling

The tear drainage apparatus evolved in terrestrial animals serving as conduits for tear flow. Obstruction of tear drainage causes a range of ocular surface disorders. Hitherto, genetics of tear duct development and obstruction has been scarcely explored. Here we report that a severe Prickle 1 hypomorph mouse line exhibited epiphora. This phenotype was due to blockage of the tear drainage by the incompletely formed nasolacrimal duct (NLD) and lacrimal canaliculi (CL). Further analysis revealed that the precocious eyelid opening, previously observed in the same type of Prickle 1 mutants, is also caused by tear duct dysplasia. A comparison of wild type, the Prickle 1 hypomorph and null mutants revealed a dose-dependent requirement of Prickle 1 for tear duct outgrowth. As a key component of a set of six Wnt/PCP core proteins, Prickle 1 usually works together with other PCP components. An investigation of expression of Wnt/PCP core genes demonstrated three of the six PCP components in tear duct, supporting the notion of context-dependent organization of PCP protein complexes. Furthermore, expression of Fgfr2/Fgf10 and p63 genes, mutations of which are associated with NLD and CL hypoplasia in human, were not altered in Prickle 1 mutant mice. Lastly, we showed that Prickle 1 expression in developing tear drainage system is conserved between mouse and human despite anatomical differences. Altogether, the study uncovered how obstruction of the tear drainage could lead to a complex ocular surface disorder, which may have genetic implications in human ocular health.

genetics↗

bioRxiv2020

Ontogenesis of the tear drainage system requires Prickle 1-controlled polarized basement membrane (BM) deposition

In terrestrial animals, lacrimal drainage apparatus evolved to serve as conduits for tear flow. Little is known about the ontogenesis of this system. Here, we investigated tear duct origin, developmental course, genetic and cellular determinants in mouse. We report that primordial tear duct (PTD) originates from junction epithelium of the joining maxillary and lateral nasal processes, which reshapes into future tear duct branches. We identified Prickle 1 as a hallmark for tear duct outgrowth, ablation of which stalled duct elongation. In particular, the disruption of basement membrane (BM) with cytoplasmic accumulation of laminin suggests aberrant protein trafficking. Mutant embryoid bodies (EBs) derived from iPSCs recapitulate BM phenotype of the PTD exhibiting defective visceral endoderm (VE), which normally expresses high level of Prickle 1. Furthermore, replenishing mutant VE with Prickle 1 completely rescued BM but not cell polarity. Taken together, our results reveal a distinct role of Prickle 1 in regulating polarized BM secretion and deposition in precedently uncharacterized tear drainage system and VE, which is independent of apicobasal polarity establishment.

developmental biology↗