From intuition to AI: evolution of small molecule representations in drug discovery.

Within drug discovery, the goal of AI scientists and cheminformaticians is to help identify molecular starting points that will develop into safe and efficacious drugs while reducing costs, time and failure rates. To achieve this goal, it is crucial to represent molecules in a digital format that makes them machine-readable and facilitates the accurate prediction of properties that drive decision-making. Over the years, molecular representations have evolved from intuitive and human-readable formats to bespoke numerical descriptors and fingerprints, and now to learned representations that capture patterns and salient features across vast chemical spaces. Among these, sequence-based and graph-based representations of small molecules have become highly popular. However, each approach has strengths and weaknesses across dimensions such as generality, computational cost, inversibility for generative applications and interpretability, which can be critical in informing practitioners' decisions. As the drug discovery landscape evolves, opportunities for innovation continue to emerge. These include the creation of molecular representations for high-value, low-data regimes, the distillation of broader biological and chemical knowledge into novel learned representations and the modeling of up-and-coming therapeutic modalities.

How do environmentally friendly antifouling alkaloids affect marine fouling microbial communities?

Most previous studies on antifouling (AF) agents have focused on the influence of biofilm formation constituted by single or multiple cultured microbial species, and very few studies have analyzed the relationship between environmentally friendly AF compounds and marine fouling microbial communities (MFMCs). This is the first investigation of the impact of three environmentally friendly alkaloids (5-chlorosclerotiamide, circumdatin F and notoamide C) produced by the deep-sea-derived fungus Aspergillus westerdijkiae on MFMCs using high-throughput Illumina sequencing in a field test. The results of this study showed that the three alkaloids could significantly decrease the coverage of marine microflora (p < 0.05) and affect the composition and diversity of MFMCs on polyvinyl chloride (PVC) plates. Furthermore, 5-chlorosclerotiamide and notoamide C could completely inhibit many macrofouler-inductive-bacteria, such as Pseudoalteromonas and Pseudomonas, and promote the anti-macrofouler-bacteria, such as Winogradskyella, from 0.21% to more than 10% of the MFMCs on PVC plates. These results suggested that 5-chlorosclerotiamide and notoamide C could influence the compositions of MFMCs and make it unfavorable for the settlement of macrofoulers, by reducing the abundance of macrofouler-inductive-bacteria and promoting the percentage of anti-macrofouler-bacteria on PVC plates. The present study provides a new way to evaluate the effect of environmentally friendly AF compounds and obtain a better understanding of the antifouling process.

Deep Insights into Gut Microbiota in Four Carnivorous Coral Reef Fishes from the South China Sea.

Investigations of gut microbial diversity among fish to provide baseline data for wild marine fish, especially the carnivorous coral reef fishes of the South China Sea, are lacking. The present study investigated the gut microbiota of four carnivorous coral reef fishes, including Oxycheilinus unifasciatus, Cephalopholis urodeta, Lutjanus kasmira, and Gnathodentex aurolineatus, from the South China Sea for the first time using high-throughput Illumina sequencing. Proteobacteria, Firmicutes, and Bacteroidetes constituted 98% of the gut microbiota of the four fishes, and 20 of the gut microbial genera recovered in this study represent new reports from marine fishes. Comparative analysis indicated that the four fishes shared a similar microbial community, suggesting that diet type (carnivorous) might play a more important role in shaping the gut microbiota of coral reef fishes than the species of fish. Furthermore, the genera Psychrobacter, Escherichia-Shigella, and Vibrio constituted the core microbial community of the four fishes, accounting for 61-91% of the total sequences in each fish. The lack of the genus Epulopiscium in the four fishes was in sharp contrast to what has been found in coral reef fishes from the Red Sea, in which Epulopiscium was shown to be the most dominant gut microbial genus in seven herbivorous coral reef fishes. In addition, while unique gut microbial genera accounted for a small proportion (8-13%) of the total sequences, many such genera were distributed in each coral reef fish species, including several genera (Endozoicomonas, Clostridium, and Staphylococcus) that are frequently found in marine fishes and 11 new reports of gut microbes in marine fishes. The present study expands our knowledge of the diversity and specificity of gut microbes associated with coral reef fishes.