Extend the benchmarking indel set by manual review using the individual cell line sequencing data from the Sequencing Quality Control 2 (SEQC2) project.

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

Microbiota, co-metabolites, and network pharmacology reveal the alteration of the ginsenoside fraction on inflammatory bowel disease.

Background: Panax ginseng Meyer (P. ginseng) is a traditional natural/herbal medicine. The amelioration on inflammatory bowel disease (IBD) activity rely mainly on its main active ingredients that are referred to as ginsenosides. However, the current literature on gut microbiota, gut microbiota-host co-metabolites, and systems pharmacology has no studies investigating the effects of ginsenoside on IBD. Methods: The present study was aimed to investigate the role of ginsenosides and the possible underlying mechanisms in the treatment of IBD in an acetic acid-induced rat model by integrating metagenomics, metabolomics, and complex biological networks analysis. In the study ten ginsenosides in the ginsenoside fraction (GS) were identified using Q-Orbitrap LC-MS. Results: The results demonstrated the improvement effect of GS on IBD and the regulation effect of ginsenosides on gut microbiota and its co-metabolites. It was revealed that 7 endogenous metabolites, including acetic acid, butyric acid, citric acid, tryptophan, histidine, alanine, and glutathione, could be utilized as significant biomarkers of GS in the treatment of IBD. Furthermore, the biological network studies revealed EGFR, STAT3, and AKT1, which belong mainly to the glycolysis and pentose phosphate pathways, as the potential targets for GS for intervening in IBD. Conclusion: These findings indicated that the combination of genomics, metabolomics, and biological network analysis could assist in elucidating the possible mechanism underlying the role of ginsenosides in alleviating inflammatory bowel disease and thereby reveal the pathological process of ginsenosides in IBD treatment through the regulation of the disordered host-flora co-metabolism pathway.

Advances in extraction, purification, structural characteristics and biological activities of hemicelluloses: A review.

Hemicelluloses, a major component of plant cell walls, are a non-cellulosic heteropolysaccharide composed of several distinct sugars that is second in abundance to cellulose, which are one of the most abundant and cheapest renewable resources on earth. Hemicelluloses structure is complex and its chemical structure varies greatly among the different plant species. In addition to its wide use in production of feed and other chemical materials, hemicelluloses are known for its remarkable biological activities that remain largely underutilised to date. Therefore, comprehensive investigations of hemicelluloses structural and biological properties would be helpful for achieving rational utilisation and high-value conversion of this underutilised substance into agents with enhanced health benefits for incorporation in drugs and health foods. In this review, details of diverse research initiatives that have enhanced our understanding of hemicelluloses properties are summarised, including hemicelluloses sources, extraction and purification methods, structural characteristics and biological activities. Furthermore, hemicelluloses structure-activity relationships and new directions for future hemicelluloses research studies are discussed.

Effects of sulfated polysaccharides from Laminaria japonica on regularating the gut microbiotan and alleviating intestinal inflammation in obese mice.

Due to their known health-enhancing properties, Laminaria japonica polysaccharides (LJP) may alleviate obesity via unknown mechanisms. This study aimed to investigate beneficial LJP effects and mechanism(s) of action using an animal obesity model (ICR mice fed a high-fat diet). First, LJP were confirmed to consist of sulfated polysaccharides via infrared spectroscopy. Next, LJP administration to mice was found to induce weight loss, reduce liver fat accumulation, and support healthy obesity-related blood serum indicator levels. Notably, LJP treatment significantly reduced TC and LDL levels and significantly increased HDL, LPL, UCP-2, and PPAR-α levels. Furthermore, examinations of tissues of LJP-treated mice revealed significantly reduced intestinal tissue inflammation as compared to corresponding results obtained for untreated obese controls. Additionally, LJP treatment relieved colonic shortening and reduced colonic levels of inflammatory factors TNF-α and IL-6. Further exploration of LJP treatment effects on mouse gut microbiota conducted via fecal 16S rRNA gene sequence-based gut microbiome profiling analysis revealed that LJP treatment increased the Bacteroidetes/Firmicutes ratio and increased gut abundances of probiotics Bacteroides acidifaciens, s_Lactobacillus intestinalis, and s_Lactobacillus murinus. In conclusion, these results collectively suggest that LJP use as a food supplement may alleviate obesity and related gut microbiota dysbiosis and intestinal inflammatory disorders.

Low-intensity focused ultrasound stimulation reverses social avoidance behavior in mice experiencing social defeat stress.

The excitatory neurons of the medial prefrontal cortex (mPFC) respond to social stimuli. However, little is known about how the neural activity is altered during social avoidance, and whether it could act as a target of low-intensity focused ultrasound stimulation (LIFUS) to rescue social deficits. The present study aimed to investigate the mechanisms of neuronal activities and inflammatory responses underlying the effect of LIFUS on social avoidance. We found that chronic LIFUS stimulation can effectively improve social avoidance in the defeated mice. Calcium imaging recordings by fiber photometry in the defeated mice showed inhibited ensemble activity during social behaviors. LIFUS instantaneously triggered the mPFC neuronal activities, and chronic LIFUS significantly enhanced their neuronal excitation related to social interactions. We further found that the excessive activation of microglial cells and the overexpression of the inflammation signaling, i.e. Toll-like receptors(TLR4)/nuclear factor-kappaB(NF-КB), in mPFC were significantly inhibited by LIFUS. These results suggest that the LIFUS may inhibit social avoidance behavior by reducing activation of the inflammatory response, increasing neuronal excitation, and protecting the integrity of the neuronal structure in the mPFC. Our findings raised the possibility of LIFUS being applied as novel neuromodulation for social avoidance treatment in neuropsychiatric diseases.

Drug-induced QT Prolongation Atlas (DIQTA) for enhancing cardiotoxicity management.

Drug-induced prolongation of the QT interval is common in a variety of pharmaceutical treatments and can lead to serious clinical outcomes. Although substantial efforts have been made to prevent drug-induced QT interval prolongation, the lack of a centralized data source remains the main obstacle to further study of the underlying mechanism and the development of effective prediction strategies. To fill this gap, we propose a schema for stratifying the risk of marketed QT prolonging drugs based on US Food and Drug Administration (FDA)-approved drug labeling and developed a Drug-Induced QT Prolongation Atlas (DIQTA). Potential application of DIQTA was shown by precision dosing in off-label use and therapeutic strategy optimization, as well as the facilitation of artificial intelligence (AI)-based modeling in predictive toxicity.

Comparative Analysis for the Performance of Long-Read-Based Structural Variation Detection Pipelines in Tandem Repeat Regions.

There has been growing recognition of the vital links between structural variations (SVs) and diverse diseases. Research suggests that, with much longer DNA fragments and abundant contextual information, long-read technologies have advantages in SV detection even in complex repetitive regions. So far, several pipelines for calling SVs from long-read sequencing data have been proposed and used in human genome research. However, the performance of these pipelines is still lack of deep exploration and adequate comparison. In this study, we comprehensively evaluated the performance of three commonly used long-read SV detection pipelines, namely PBSV, Sniffles and PBHoney, especially the performance on detecting the SVs in tandem repeat regions (TRRs). Evaluated by using a robust benchmark for germline SV detection as the gold standard, we thoroughly estimated the precision, recall and F1 score of insertions and deletions detected by the pipelines. Our results revealed that all these pipelines clearly exhibited better performance outside TRRs than that in TRRs. The F1 scores of Sniffles in and outside TRRs were 0.60 and 0.76, respectively. The performance of PBSV was similar to that of Sniffles, and was generally higher than that of PBHoney. In conclusion, our findings can be benefit for choosing the appropriate pipelines in real practice and are good complementary to the application of long-read sequencing technologies in the research of rare diseases.

Quantitative Structure-Activity Relationship (QSAR) Model for the Severity Prediction of Drug-Induced Rhabdomyolysis by Using Random Forest.

Drug-induced rhabdomyolysis (DIR) is a rare and potentially life-threatening muscle injury that is characterized by low incidence and high risk. To our best knowledge, the performance of the current predictive models for the early detection of DIR is suboptimal because of the scarcity and dispersion of DIR cases. Therefore, on the basis of the curated drug information from the Drug-Induced Rhabdomyolysis Atlas (DIRA) database, we proposed a random forest (RF) model to predict the DIR severity of the marketed drugs. Compared with the state-of-art methods, our proposed model outperformed extreme gradient boosting, support vector machine, and logistic regression in distinguishing the Most-DIR concern drugs from the No-DIR concern drugs (Matthews correlation coefficient (MCC) and recall rate of our model were 0.46 and 0.81, respectively). Our model was subsequently applied to predicting the potentially serious DIR for 1402 drugs, which were reported to cause DIR by the postmarketing DIR surveillance data in the FDA Spontaneous Adverse Events Reporting System (FAERS). As a result, 62.7% (94) of drugs ranked in the top 150 drugs with the Most-DIR concerns in FAERS can be identified by our model. The top four drugs (odds ratio >30) including acepromazine, rapacuronium, oxyphenbutazone, and naringenin were correctly predicted by our model. In conclusion, the RF model can well predict the Most-DIR concern drug only based on the chemical structure information and can be a facilitated tool for early DIR detection.

Recent progress in polysaccharides from Panax ginseng C. A. Meyer.

Panax ginseng C. A. Meyer (P. ginseng) has a long history of medicinal use and can treat a variety of diseases. P. ginseng contains a variety of active ingredients, such as saponins, polypeptides, volatile oils, and polysaccharides. Among them, saponins have always been considered as the main components responsible for its pharmacological activities. However, more and more studies have shown that polysaccharides play an indispensable role in the medicinal value of ginseng. Modern biological and medical studies have found that ginseng polysaccharides have complex structural characteristics and diverse biological activities, such as immune regulation, anti-tumor, antioxidant, hypoglycemic, and anti-radiation functions, among others. Additionally, the structural characteristics of ginseng polysaccharides are closely related to their activity. In this review, the research background, extraction, purification, structural characteristics, and biological activities of ginseng polysaccharides from different parts of P. ginseng (roots, flowers stems and leaves, and berries) under different growth conditions (artificially cultivated ginseng, mountain ginseng, and wild ginseng) are summarized. The structural characteristics of purified polysaccharides were reviewed. Meanwhile, their biological activities were introduced, and some possible mechanisms were listed. Furthermore, the structure-activity relationship of polysaccharides was discussed. Some research perspectives for the study of ginseng polysaccharides were also provided.

[Enhanced Treatment of Petrochemical Secondary Effluent by Biological Aerated Filter (Fe2+)-Ozonation Process].

Two parallel biological aerated filters (BAF)-ozonation,named as number 1(feeding with FeSO4·7H2O) and number 2,were used to treat petrochemical secondary effluent.The effect of FeSO4·7H2O on COD and phosphorus removal by BAF-ozonation was studied.Molecular weight distribution,three-dimensional fluorescence scan and gas chromatography-mass spectrometry (GC-MS) were used to analyze water quality before and after BAF-ozonation.The results showed the average COD and TP concentrations were 82.91 mg·L-1 and 1.37 mg·L-1,respectively.When the dosage of FeSO4·7H2O was 9 mg·L-1,the average removal rates of COD and TP were 52.20% and 71.50%,respectively.The average COD removal rate in number 1 combined process was 17.15%,which was higher than that in number 2 combined process.The TP removal rate in number 1 combined process was increased by 51.81%.The percentage of dissolved organic matters with relative molecular weight less than 1×103 was 52% in the raw wastewater.However,the percentage increased to 75% when treated by number 1 combined process and the removal rate of various molecular weight organics was increased.Three-dimensional fluorescence analysis showed that the dosage of FeSO4·7H2O could improve the removal of fluorescent substances.GC-MS results showed that the number and concentration of organics were reduced after number 1 combined process in comparison with number 2 combined process.BAF-ozone could be enhanced by FeSO4·7H2O when treating petrochemical secondary effluent.

Innovative combination of Fe2+-BAF and ozonation for enhancing phosphorus and organic micropollutants removal treating petrochemical secondary effluent.

Two sets of BAF - ozonation systems, with (System-A) and without (System-B) Fe2+ dosing into BAF, were used for organic micropollutants (OMPs) and phosphorus removal in the advanced treatment of petrochemical secondary effluent. Pilot scale study showed that when the influent COD, TP and TSS were 73.0, 1.40 and 24.6mgL-1, the effluent COD, TP and TSS were 48.9, 0.32, 7.78mgL-1 for System-A with the ozone and Fe2+ dosage of 25mgL-1 and 0.08mmolL-1, and 60.2, 1.16, 6.44mgL-1 for System-B with the ozone dosage of 25mgL-1. The dosage of Fe2+ into the BAF significantly enhanced the TP and OMPs removal ability. Exactly, the residual Fe2+ in the BAF-A effluent stimulated the catalytic ozonation in the following ozone unit. Therefore, the OMPs removal in System-A was obviously better than that in System-B. The dosage of Fe2+ from 0.02 to 0.10mmolL-1 had slight adverse effect on the biofilm activity in BAF. Based on the TP and OMPs removal ability, the System-B is selected as a proposed process for the advanced treatment of petrochemical secondary effluent.