Deep Neural Networks (DNNs) are renowned for their high accuracy and versatility, which has led to their application in many fields of research, including biology. However, this accuracy often comes at the expense of interpretability, making it challenging to reason about the inner workings of most DNNs. Particularly in biological research, understanding the mechanisms behind specific outcomes is highly valuable. To elucidate the latent space of DNNs in the context of cancer biology, we introduce GONNECT: a Gene Ontology-derived Neural Network for Explainable Cancer Typing. GONNECT incorporates biological prior knowledge from the Gene Ontology (GO) directly into its network architecture, enabling interpretability through model structure. Using an autoencoder framework, we evaluate GONNECT as both encoder and decoder module and demonstrate its ability to learn which biological processes are distinctive for different cancer types. Furthermore, we show how a variant including soft links (GONNECT-SL) can expand on current knowledge by proposing new interactions between biological processes. GONNECT is flexible both in the amount of prior knowledge it incorporates and the set of input genes, and can potentially be applied in modeling of gene perturbation effects and drug target discovery.

Single-cell RNA sequencing (scRNAseq) is a measuring technique of gene expressions in single cells that has allowed researchers to tackle Alzheimer’s disease (AD) in many ways. Single-cell data has been joined with machine learning to classify brain cells as affected by AD. However, not much is known regarding the usage of such classification models in a spatial setting. This paper analyzes how models trained on scRNAseq data can be used to find AD properties of single cells when measuring them with spatially resolved transcriptomics. With that we study the hypothesis that cells labeled as affected by the disease should appear closer to amyloid plaques, than those that are unaffected. To find out if this holds, three models are used to classify single cells spatially and their predictions are analyzed. Two single-cell datasets are used for training, each giving a drastically different classification outcome. The models do not come to a consensus on the hypothesis’ validity either, as the analysis finds no significant correlation between the variables.

Alzheimer's Disease (AD) is a complex heterogeneous disease and is the leading cause of dementia around the world. Treatment options remain limited and the underlying mechanisms are not yet fully understood. To get more insight on this celular level, single-cell gene expression data can be used. It has proven to be effective with machine learning for tasks like cell type classification. While prior studies have explored AD classification using scRNA-seq, this has only been a binary classification. Severity of AD is classified using multiple measures, ranging from cognitive ability scores, to neuro pathological measures. This research explores the possibility of expanding the binary prediction of AD by including these measures for AD severity. In addition, given that these measures are associated, we also investigate if Multi Task Learning (MTL) models can improve the predictions by learning multiple AD related data points. If successful, this approach can give additional analysis into key tasks, genes and/or cells (sub)types that drive the models, which would lead to more possibilities for personalized treatment options, alongside more insight into the development of AD in the brain. We used a three-layer neural network architecture alongside a translation from cellular level to individual level to make individual-level predictions. Results show that Cognitive Ability can be classified best, but overal performance is only slightly above Naive Bayes. Furthermore, MTL does not appear to have any measurable positive effect on scores compared to single task models. A link to the github repository is available at \url{https://github.com/WillemDieleman/ADseverityCSE3000}.