CRISPR/Cas9 is a popular genome editing technology, yet its clinical application is hindered by off-target effects. Many deep learning-based methods are available for off-target prediction. However, few can predict off-target activities with insertions or deletions (indels) between single guide RNA and DNA sequence pairs.
View Article and Find Full Text PDFCRISPR/Cas9 has been applied to edit the genome of various organisms, but our understanding of editing outcomes at specific sites after Cas9-mediated DNA cleavage is still limited. Several deep learning-based methods have been proposed for repair outcome prediction; however, there is still room for improvement in terms of performance regarding frameshifts and model interpretability. Here, we present DeepIndel, an end-to-end multi-label regression model for predicting repair outcomes based on the BERT-base module.
View Article and Find Full Text PDFCRISPR/Cas9 is a powerful genome-editing tool in biology, but its wide applications are challenged by a lack of knowledge governing single-guide RNA (sgRNA) activity. Several deep-learning-based methods have been developed for the prediction of on-target activity. However, there is still room for improvement.
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
March 2024
Clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) is a new generation of gene editing technology, which relies on single guide RNA to identify specific gene sites and guide Cas9 nuclease to edit specific location in the genome. However, the off-target effect of this technology hampers its development. In recent years, several deep learning models have been developed for predicting the CRISPR/Cas9 off-target activity, which contributes to more efficient and safe gene editing and gene therapy.
View Article and Find Full Text PDFOff-target effects of CRISPR/Cas9 can lead to suboptimal genome editing outcomes. Numerous deep learning-based approaches have achieved excellent performance for off-target prediction; however, few can predict the off-target activities with both mismatches and indels between single guide RNA (sgRNA) and target DNA sequence pair. In addition, data imbalance is a common pitfall for off-target prediction.
View Article and Find Full Text PDFIn silico design of single guide RNA (sgRNA) plays a critical role in clustered regularly interspaced, short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system. Continuous efforts are aimed at improving sgRNA design with efficient on-target activity and reduced off-target mutations. In the last 5 years, an increasing number of deep learning-based methods have achieved breakthrough performance in predicting sgRNA on- and off-target activities.
View Article and Find Full Text PDFBicyclic boronates play critical roles in the discovery of functional materials and antibacterial agents, especially against deadly bacterial pathogens. Their practical and convenient preparation is in high demand but with great challenge. Herein, we report an efficient strategy for the preparation of bicyclic boronates through metal-free heteroatom-directed alkenyl sp-C‒H borylation.
View Article and Find Full Text PDFThe coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a major public health crisis, posing a significant threat to human well-being. Despite the availability of vaccines, COVID-19 continues to spread owing to the emergence of SARS-CoV-2 mutants. This highlights the urgent need for the discovery of more effective drugs to combat COVID-19.
View Article and Find Full Text PDFIn nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess).
View Article and Find Full Text PDFCells of members of the family , phylum , are generally obligate anaerobic rods. Strains D2Q-14 and D2Q-11 were isolated from sediment of the saline lake Manisi in the Xinjiang Uygur Autonomous Region, PR China. In this study, we employed a polyphasic approach and whole genome analysis of the two isolates.
View Article and Find Full Text PDFMicroRNA exerts an important regulatory role in almost all the biological process, including hair follicle development in Liaoning Cashmere goat. In order to improve the Cashmere performance of goat, the regulatory role of microRNA in hair follicle cycle has drawn hotspot attention. However, the molecular mechanisms of miRNA-1-3p involved in hair follicle development are poorly understood.
View Article and Find Full Text PDFEmerging evidence indicates that circRNA can regulate various diseases. However, the mechanisms of circRNA in these diseases have not been fully understood. Therefore, detecting potential circRNA-disease associations has far-reaching significance for pathological development and treatment of these diseases.
View Article and Find Full Text PDFMetabolic syndrome (MetS) is a group of physiological states of metabolic disorders, which may increase the risk of diabetes, cardiovascular and other diseases. Therefore, it is of great significance to predict the onset of MetS and the corresponding risk factors. In this study, we investigate the risk prediction for MetS using a data set of 67,730 samples with physical examination records of three consecutive years provided by the Department of Health Management, Nanfang Hospital, Southern Medical University, P.
View Article and Find Full Text PDFArch Microbiol
December 2021
A novel extremely halophilic archaeon, designated WN019, was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China. Cells of WN019 were aerobic, motile, and pleomorphic rod-shaped, 0.5-0.
View Article and Find Full Text PDFArch Microbiol
December 2021
Strain WRN001, a Gram-staining-negative, strictly aerobic, non-motile bacterium was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China (38°46' N, 117°13' E). Cells of strain WRN001 were 0.3-0.
View Article and Find Full Text PDFA Gram-stain-negative, ovoid or rod-shaped, non-flagellated, motile-by-gliding and aerobic bacteria, designated S10-8, was isolated from marine sediment of the Yellow Sea. Colonies of strain S10-8 had a pink-red pigmentation and its cells were approximately 0.5-0.
View Article and Find Full Text PDFExploration of the diastereodivergent synthesis of spirocyclic oxindoles has been challenging. Herein we report asymmetric [3 + 2] annulations of isatin-derived Morita-Baylis-Hillman (MBH) carbonates and 5-alkenylthiazol-4(5)-ones. Interestingly, two different chiral catalysts, amide-phosphine and 4-dimethylaminopyridine (DMAP)-thiourea, could lead to two kinds of diastereomeric dispiro oxindoles with three contiguous stereogenic centers.
View Article and Find Full Text PDFQuorum sensing (QS), usually performed by -acyl-homoserine lactones (AHLs) in Gram-staining-negative bacteria, plays an important role in plant-bacteria interactions. M15 is a plant-growth-promoting rhizobacterium (PGPR) isolated from rice roots. In this study, we found a QS system in the endogenous plasmid of M15 and detected the activity of AHLs by a bioassay method.
View Article and Find Full Text PDFA Gram-staining-positive, aerobic, non-endospore-forming, coccus-shaped, non-flagellated, and non-motile bacterium, designated WN024, was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China. Cells of strain WN024 were catalase- and oxidase-positive. The isolate was able to grow between 20 and 45 °C (optimal at 33-37 °C), pH 6.
View Article and Find Full Text PDFCRISPR/Cas9 is a preferred genome editing tool and has been widely adapted to ranges of disciplines, from molecular biology to gene therapy. A key prerequisite for the success of CRISPR/Cas9 is its capacity to distinguish between single guide RNAs (sgRNAs) on target and homologous off-target sites. Thus, optimized design of sgRNAs by maximizing their on-target activity and minimizing their potential off-target mutations are crucial concerns for this system.
View Article and Find Full Text PDFA Gram-staining-positive, endospore-forming, aerobic strain, designed WN066, was isolated from saline-alkali wetland soil of Tianjin, China. Phylogenetic analysis based on 16S rRNA gene sequence indicated WN066 was a member of the genus of Bacillus, and most closely related to Bacillus drentensis DSM 15600 (98.9%), Bacillus cucumis CCM 8651 (98.
View Article and Find Full Text PDFThe rational design based on a deep understanding of the present reaction mechanism is an important, viable approach to discover new organic transformations. β-Hydrogen elimination from palladium complexes is a fundamental reaction in palladium catalysis. Normally, the eliminated β-hydrogen has to be attached to a sp-carbon.
View Article and Find Full Text PDFA Gram staining-negative, halophilic, aerobic, non-motile bacteria, designated strain WN018, were isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China (38°46'N, 117°13'E). Cells of strain WN018 were short rod-shaped, 0.3-0.
View Article and Find Full Text PDFA Gram-staining-negative, halophilic, aerobic, oval-shaped or vibrio-shaped, motile by a polar flagellum strain, designated YL5-2, was isolated from natural saline-alkaline wetland soil of Binhai new district, Tianjin, China. Strain YL5-2 grew optimally at 35 °C, pH 7.5-8.
View Article and Find Full Text PDFTwo extremely halophilic archaeal strains, designated SB29 and SB3, were isolated from the brine-seawater interface of Discovery Deep in the Red Sea. Cells of both strains were pleomorphic (irregular polyhedrals, ovals, and rods) and stained Gram-negative; colonies were pigmented pink. The sequence similarity of the 16S rRNA gene of strain SB29 with that of its most closely related validly described species ( DSM 16227) and that of strain SB3 with its closest validly described relative ( ATCC 35960) was 98.
View Article and Find Full Text PDF