The thesis project is an essential step to obtain an MSc degree. Within STEM and Life Sciences disciplines, computational theses have specific characteristics that differentiate them from wet laboratory ones. In this article, we present Ten simple rules to direct and support Master students who are about to start a computational research project for their Master thesis. We begin by recommending defining the personal learning goals for the project; we then highlight specific pitfalls that computational students might encounter during their work, such as procrastination by computation or wasting time while attempting to reinvent computational tools. We provide the students a series of suggestions on how to work following FAIR principles, learn new computing languages, and think ahead for computational challenges. We hope that these 10 simple rules will provide Master students with a framework for the successful completion of their computational thesis.

Deep learning applications have had a profound impact on many scientific fields, including functional genomics. Deep learning models can learn complex interactions between and within omics data; however, interpreting and explaining these models can be challenging. Interpretability is essential not only to help progress our understanding of the biological mechanisms underlying traits and diseases but also for establishing trust in these model's efficacy for healthcare applications. Recognizing this importance, recent years have seen the development of numerous diverse interpretability strategies, making it increasingly difficult to navigate the field. In this review, we present a quantitative analysis of the challenges arising when designing interpretable deep learning solutions in functional genomics. We explore design choices related to the characteristics of genomics data, the neural network architectures applied, and strategies for interpretation. By quantifying the current state of the field with a predefined set of criteria, we find the most frequent solutions, highlight exceptional examples, and identify unexplored opportunities for developing interpretable deep learning models in genomics.

Unsupervised learning, particularly clustering, plays a pivotal role in disease subtyping and patient stratification, especially with the abundance of large-scale multi-omics data. Deep learning models, such as variational autoencoders (VAEs), can enhance clustering algorithms by leveraging inter-individual heterogeneity. However, the impact of confounders-external factors unrelated to the condition, e.g. batch effect or age-on clustering is often overlooked, introducing bias and spurious biological conclusions. In this work, we introduce four novel VAE-based deconfounding frameworks tailored for clustering multi-omics data. These frameworks effectively mitigate confounding effects while preserving genuine biological patterns. The deconfounding strategies employed include (i) removal of latent features correlated with confounders, (ii) a conditional VAE, (iii) adversarial training, and (iv) adding a regularization term to the loss function. Using real-life multi-omics data from The Cancer Genome Atlas, we simulated various confounding effects (linear, nonlinear, categorical, mixed) and assessed model performance across 50 repetitions based on reconstruction error, clustering stability, and deconfounding efficacy. Our results demonstrate that our novel models, particularly the conditional multi-omics VAE (cXVAE), successfully handle simulated confounding effects and recover biologically driven clustering structures. cXVAE accurately identifies patient labels and unveils meaningful pathological associations among cancer types, validating deconfounded representations. Furthermore, our study suggests that some of the proposed strategies, such as adversarial training, prove insufficient in confounder removal. In summary, our study contributes by proposing innovative frameworks for simultaneous multi-omics data integration, dimensionality reduction, and deconfounding in clustering. Benchmarking on open-access data offers guidance to end-users, facilitating meaningful patient stratification for optimized precision medicine.

This paper presents a semi-supervised approach for intrusion detection. The method extends the unsupervised multivariate statistical network monitoring approach based on the principal component analysis by introducing a supervised optimization technique to learn the optimum scaling in the input data. It inherits the advantages of the unsupervised strategy, capable of uncovering new threats, with that of supervised strategies, capable of learning the pattern of a targeted threat. The supervised learning is based on an extension of the gradient descent method based on partial least squares (PLS). Moreover, we enhance this method by using sparse PLS variants. The practical application of the system is demonstrated on a recently published real case study, showing relevant improvements in detection performance and in the interpretation of the attacks.

Summary: To unlock the full potential of genome data and to enhance data interoperability and reusability of genome annotations we have developed SAPP, a Semantic Annotation Platform with Provenance. SAPP is designed as an infrastructure supporting FAIR de novo computational genomics but can also be used to process and analyze existing genome annotations. SAPP automatically predicts, tracks and stores structural and functional annotations and associated dataset- and element-wise provenance in a Linked Data format, thereby enabling information mining and retrieval with Semantic Web technologies. This greatly reduces the administrative burden of handling multiple analysis tools and versions thereof and facilitates multi-level large scale comparative analysis. Availability and implementation: SAPP is written in JAVA and freely available at https://gitlab.com/sapp and runs on Unix-like operating systems. The documentation, examples and a tutorial are available at https://sapp.gitlab.io. Contact: [email protected] or [email protected].