Identifying Synergistic Components of Botanical Fungicide Formulations Using Interpretable Graph Neural Networks.

Botanical formulations are promising candidates for developing new biopesticides that can protect crops from pests and diseases while reducing harm to the environment. These biopesticides can be combined with permeation enhancer compounds to boost their efficacy against pests and fungal diseases. However, finding synergistic combinations of these compounds is challenging due to the large and complex chemical space. In this paper, we propose a novel deep learning method that can predict the synergy of botanical products and permeation enhancers based on in vitro assay data. Our method uses a weighted combination of component feature vectors to represent the input mixtures, which enables the model to handle a variable number of components and to interpret the contribution of each component to the synergy. We also employ an ensemble of interpretation methods to provide insights into the underlying mechanisms of synergy. We validate our method by testing the predicted synergistic combinations in wet-lab experiments and show that our method can discover novel and effective biopesticides that would otherwise be difficult to find. Our method is generalizable and applicable to other domains, where predicting mixtures of chemical compounds is important.

Pan-cancer integrative analysis of whole-genome De novo somatic point mutations reveals 17 cancer types.

BACKGROUND: The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence, there is no definitive treatment for most cancer types. This reveals the importance of developing new pipelines to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. RESULTS: In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in many samples to identify cancer subtypes. We apply our pipeline to 12,270 samples collected from the international cancer genome consortium, covering 19 cancer types. As a result, we identify 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways. CONCLUSIONS: This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. Additionally, we analyze the mutational signatures for samples in each subtype, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on "gene-motif" suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer .