DROEG: a method for cancer drug response prediction based on omics and essential genes integration.

Predicting therapeutic responses in cancer patients is a major challenge in the field of precision medicine due to high inter- and intra-tumor heterogeneity. Most drug response models need to be improved in terms of accuracy, and there is limited research to assess therapeutic responses of particular tumor types. Here, we developed a novel method DROEG (Drug Response based on Omics and Essential Genes) for prediction of drug response in tumor cell lines by integrating genomic, transcriptomic and methylomic data along with CRISPR essential genes, and revealed that the incorporation of tumor proliferation essential genes can improve drug sensitivity prediction. Concisely, DROEG integrates literature-based and statistics-based methods to select features and uses Support Vector Regression for model construction. We demonstrate that DROEG outperforms most state-of-the-art algorithms by both qualitative (prediction accuracy for drug-sensitive/resistant) and quantitative (Pearson correlation coefficient between the predicted and actual IC50) evaluation in Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopedia datasets. In addition, DROEG is further applied to the pan-gastrointestinal tumor with high prevalence and mortality as a case study at both cell line and clinical levels to evaluate the model efficacy and discover potential prognostic biomarkers in Cisplatin and Epirubicin treatment. Interestingly, the CRISPR essential gene information is found to be the most important contributor to enhance the accuracy of the DROEG model. To our knowledge, this is the first study to integrate essential genes with multi-omics data to improve cancer drug response prediction and provide insights into personalized precision treatment.

N-Acyl-Homoserine Lactone (AHL)-Mediated Microalgal-Bacterial Communication Driving Chlorella-Activated Sludge Bacterial Biofloc Formation.

N-acyl-homoserine lactones (AHLs) as autoinducers of Gram-negative bacteria for quorum sensing regulation have shown positive effects on the production of aromatic proteins in extracellular polymeric substances (EPSs) during bioflocculation. To investigate the role of AHLs in aromatic protein production, a Chlorella-bacteria system with great bioflocculation was established via fed-batch cultivation. Tryptophan and aromatic proteins as the main compounds in the EPS of bioflocs showed an increasing trend during fed-batch cultivation. The Chlorella cells only secreted tryptophan rather than aromatic proteins during axenic cultivation. N-dodecanoyl-l-homoserine lactone (C12-HSL) was correlated with the flocculation activity and extracellular protein content of bioflocs during fed-batch cultivation. The addition of exogenous C12-HSL enhanced the flocculation activity of the Chlorella-bacteria system and aromatic protein production in the EPS. Chlorella cells sensed exogenous C12-HSL and significantly upregulated the aromatic protein synthesis pathway during axenic cultivation. In addition, vanillin as a quorum-sensing inhibitor suppressed the positive effect of C12-HSL on flocculation activity and aromatic protein production and synthesis. This result indicated that vanillin intercepts the response of Chlorella cells to C12-HSL. Overall, C12-HSL is supposed to be an important signal molecule to achieve communication between Chlorella and Gram-negative bacteria and subsequently induce Chlorella cells to produce aromatic proteins for biofloc formation.

Nitrification performance evaluation of activated sludge under high potassium ion stress during high-ammonia nitrogen organic wastewater treatment.

The recycling reverse osmosis (RO) membrane concentrate of some high-ammonia nitrogen (NH4+-N) organic wastewater to the biological unit could cause potassium ion (K+) accumulation, thereby affecting the removal of NH4+-N by activated sludge. Thus, the effects of high K+ stress on activated sludge nitrification performance was studied. The results showed that the high K+ stress promoted the floc sludge to produce more extracellular polymers (EPS), which accelerated the sludge sedimentation and enriched the biomass in sequential batch reactors (SBRs). The ammonia oxidation process and nitrite (NO2--N) oxidation process were further analyzed in the nitrification process. High K+ stress enriched ammonia oxidizing bacteria (AOB), which ensured the efficient ammonia oxidation process in SBRs, and ensured the removal rate of NH4+-N was maintained above 93%. However, high K+ stress (15g/L KCl) inhibited the activity of NO2--N oxidizing bacteria (NOB) and reduced the abundance of NOB, thus leading to the accumulation of NO2--N, and finally worsened the nitrification performance of activated sludge. In short, the performance of activated sludge will not be inhibited when the K+ in the wastewater does not exceed 5.23 g/L. The results could provide a reference for the optimization of the biological performance in treating high-NH4+-N organic wastewater with activated sludge coupled RO membrane treatment process.