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Up to half of the senior dogs suffer from canine cognitive dysfunction syndrome (CCDS), the diagnosis method relies on subjective questionnaires such as canine cognitive dysfunction rating (CCDR) scores. Therefore, the necessity of objective diagnosis is emerging. Here, we developed blood-based biomarkers for CCDS early detection. Blood samples from dogs with CCDR scores above 25 were analyzed, and the biomarkers retinol-binding protein 4 (RBP4), C-X-C-motif chemokine ligand 10 (CXCL10), and NADPH oxidase 4 (NOX4) were validated against neurodegenerative models. Lower biomarker levels were correlated with higher CCDR scores, indicating cognitive decline. Machine-learning analysis revealed the highest predictive accuracy when analyzing the combination of RBP4 and NOX4 using the support vector machine algorithm and confirmed potential diagnostic biomarkers. These results suggest that blood-based biomarkers can notably improve CCDS early detection and treatment, with implications for neurodegenerative disease management in both animals and humans.

ObjectivesAs the public's interest in companion dogs grows, health issues in these animals are also emerging, necessitating the optimization of whole exome sequencing (WES) as a valuable method for disease prediction. While WES targeting the human genome is well established, WES targeting the canine genome is understudied, and there is a need to find effective analysis kits.MethodsWe compared and analyzed the performance of three WES kits from Twist and Agilent using the canine genome as the target to perform genetic analysis of canine diseases effectively. The levels of total reads, the duplication rate, and variant calling in canine genomic DNA samples from seven healthy dogs (three beagles, one bichon fry, one maltese, one welsh corgi, and one mixed breed) without any interventions were examined through WES via Twist and Agilent kits.ResultsWe found that while Twist had the lowest total read number, the number of reads in the SSXT series was significantly (PConclusionThe most important performance of the kit, the number of variants detected, was 48,302 for Twist and 130,506 for SSXT (O/N). On the basis of the performance comparison results, SSXT (O/N) was found to have the best performance.

Abstract In this paper, a reinforcement learning model is proposed that can maximize the predicted binding affinity between a generated molecule and target proteins. The model used to generate molecules in the proposed model was the Stacked Conditional Variation AutoEncoder (Stack-CVAE), which acts as an agent in reinforcement learning so that the resulting chemical formulas have the desired chemical properties and show high binding affinity with specific target proteins. We generated 1000 chemical formulas using the chemical properties of sorafenib and the three target kinases of sorafenib. Then, we confirmed that Stack-CVAE generates more of the valid and unique chemical compounds that have the desired chemical properties and predicted binding affinity better than other generative models. More detailed analysis for 100 of the top scoring molecules show that they are novel ones not found in existing chemical databases. Moreover, they reveal significantly higher predicted binding affinity score for Raf kinases than for other kinases. Furthermore, they are highly druggable and synthesizable.

Precise prognosis of cancer patients is important because it is associated with suggesting appropriate therapeutic strategies. Several computational and statistical methods have been proposed, but further improvement of these methods in terms of prediction accuracy is required. This paper presents a deep learning-based method for learning networks of prognostic genes, instead of only individual biomarker genes, for more accurate cancer prognosis prediction. This method utilizes generative adversarial networks, where the generator uses a biological network instead of a traditional fully connected network to learn the distributions of gene expression (mRNA), copy number variation, single nucleotide polymorphism, and DNA methylation data from cancer patients. The proposed model was applied to seven cancer types and exhibited higher prediction accuracy as compared to the existing state-of-the-art methods. On average, the area under the curve (AUC) was improved by 4% compared to the best performing existing methods for seven cancer types. In particular, for pancreatic adenocarcinoma, AUC was improved by 27.9%. The identified prognostic genes were reproducible and functionally meaningful. To the best of our knowledge, the proposed method represents the first attempt to learn genetic networks from multi-omics data.

Abstract Machine learning may be a powerful approach to more accurate identification of genes that may serve as prognosticators of cancer outcomes using various types of omics data. However, to date, machine learning approaches have shown limited prediction accuracy for cancer outcomes, primarily owing to small sample numbers and relatively large number of features. In this paper, we provide a description of GVES (Gene Vector for Each Sample), a proposed machine learning model that can be efficiently leveraged even with a small sample size, to increase the accuracy of identification of genes with prognostic value. GVES, an adaptation of the continuous bag of words (CBOW) model, generates vector representations of all genes for all samples by leveraging gene expression and biological network data. GVES clusters samples using their gene vectors, and identifies genes that divide samples into good and poor outcome groups for the prediction of cancer outcomes. Because GVES generates gene vectors for each sample, the sample size effect is reduced. We applied GVES to six cancer types and demonstrated that GVES outperformed existing machine learning methods, particularly for cancer datasets with a small number of samples. Moreover, the genes identified as prognosticators were shown to reside within a number of significant prognostic genetic pathways associated with pancreatic cancer.

Accurate prediction of cancer stage is important in that it enables more appropriate treatment for patients with cancer. Many measures or methods have been proposed for more accurate prediction of cancer stage, but recently, machine learning, especially deep learning-based methods have been receiving increasing attention, mostly owing to their good prediction accuracy in many applications. Machine learning methods can be applied to high throughput DNA mutation or RNA expression data to predict cancer stage. However, because the number of genes or markers generally exceeds 10,000, a considerable number of data samples is required to guarantee high prediction accuracy. To solve this problem of a small number of clinical samples, we used a Generative Adversarial Networks (GANs) to augment the samples. Because GANs are not effective with whole genes, we first selected significant genes using DNA mutation data and random forest feature ranking. Next, RNA expression data for selected genes were expanded using GANs. We compared the classification accuracies using original dataset and expanded datasets generated by proposed and existing methods, using random forest, Deep Neural Networks (DNNs), and 1-Dimensional Convolutional Neural Networks (1DCNN). When using the 1DCNN, the F1 score of GAN5 (a 5-fold increase in data) was improved by 39% in relation to the original data. Moreover, the results using only 30% of the data were better than those using all of the data. Our attempt is the first to use GAN for augmentation using numeric data for both DNA and RNA. The augmented datasets obtained using the proposed method demonstrated significantly increased classification accuracy for most cases. By using GAN and 1DCNN in the prediction of cancer stage, we confirmed that good results can be obtained even with small amounts of samples, and it is expected that a great deal of the cost and time required to obtain clinical samples will be reduced. The proposed sample augmentation method could also be applied for other purposes, such as prognostic prediction or cancer classification.