Abstract
BackgroundTobacco smoke is the main cause of preventable mortality worldwide. Smoking increases the risk of developing many diseases and has been proposed as an aging accelerator. Yet, the molecular mechanisms driving smoking-related health decline and aging acceleration in most tissues remain unexplored.MethodsHere, we use data from the Genotype-Tissue Expression Project (GTEx) to perform a characterization of the effect of cigarette smoking across human tissues. We perform a multi-tissue analysis across 46 human tissues. Our multi-omics characterization includes analysis of gene expression, alternative splicing, DNA methylation, and histological alterations. We further analyze ex-smoker samples to assess the reversibility of these molecular alterations upon smoking cessation.ResultsWe show that smoking impacts tissue architecture and triggers systemic inflammation. We find that in many tissues, the effects of smoking significantly overlap those of aging. Specifically, both age and smoking upregulate inflammatory genes and drive hypomethylation at enhancers (odds ratio (OR) = 2). In addition, we observe widespread smoking-driven hypermethylation at target regions of the Polycomb repressive complex (OR = 2), which is a well-known aging effect. Smoking-induced epigenetic changes overlap causal aging CpGs, suggesting that these methylation changes may directly mediate the aging acceleration observed in smokers. Finally, we find that smoking effects that are shared with aging are more persistent over time.ConclusionOverall, our multi-tissue and multi-omic analysis of the effects of cigarette smoking provides an extensive characterization of the impact of tobacco smoke across tissues and unravels the molecular mechanisms driving smoking-induced tissue homeostasis decline and aging acceleration.

Abstract
Breakthroughs in sequencing technologies led to an exponential growth of genomic data, providing novel biological insights and therapeutic applications. However, analyzing large amounts of sensitive data raises key data privacy concerns, specifically when the information is outsourced to untrusted third-party infrastructures for data storage and processing (e.g., cloud computing). We introduce Gyosa, a secure and privacy-preserving distributed genomic analysis solution. By leveraging trusted execution environments (TEEs), Gyosa allows users to confidentially delegate their GWAS analysis to untrusted infrastructures. Gyosa implements a computation partitioning scheme that reduces the computation done inside the TEEs while safeguarding the users' genomic data privacy. By integrating this security scheme in Glow, Gyosa provides a secure and distributed environment that facilitates diverse GWAS studies. The experimental evaluation validates the applicability and scalability of Gyosa, reinforcing its ability to provide enhanced security guarantees.

Abstract
AbstractBreakthroughs in sequencing technologies led to an exponential growth of genomic data, providing unprecedented biological in-sights and new therapeutic applications. However, analyzing such large amounts of sensitive data raises key concerns regarding data privacy, specifically when the information is outsourced to third-party infrastructures for data storage and processing (e.g., cloud computing). Current solutions for data privacy protection resort to centralized designs or cryptographic primitives that impose considerable computational overheads, limiting their applicability to large-scale genomic analysis.We introduce Gyosa, a secure and privacy-preserving distributed genomic analysis solution. Unlike in previous work, Gyosafollows a distributed processing design that enables handling larger amounts of genomic data in a scalable and efficient fashion. Further, by leveraging trusted execution environments (TEEs), namely Intel SGX, Gyosaallows users to confidentially delegate their GWAS analysis to untrusted third-party infrastructures. To overcome the memory limitations of SGX, we implement a computation partitioning scheme within Gyosa. This scheme reduces the number of operations done inside the TEEs while safeguarding the users’ genomic data privacy. By integrating this security scheme inGlow, Gyosaprovides a secure and distributed environment that facilitates diverse GWAS studies. The experimental evaluation validates the applicability and scalability of Gyosa, reinforcing its ability to provide enhanced security guarantees. Further, the results show that, by distributing GWASes computations, one can achieve a practical and usable privacy-preserving solution.

Abstract
Aging involves complex biological processes leading to the decline of living organisms. As population lifespan increases worldwide, the importance of identifying factors underlying healthy aging has become critical. Integration of multi-modal datasets is a powerful approach for the analysis of complex biological systems, with the potential to uncover novel aging biomarkers. In this study, we leveraged publicly available epigenomic, transcriptomic and telomere length data along with histological images from the Genotype-Tissue Expression project to build tissue-specific regression models for age prediction. Using data from two tissues, lung and ovary, we aimed to compare model performance across data modalities, as well as to assess the improvement resulting from integrating multiple data types. Our results demostrate that methylation outperformed the other data modalities, with a mean absolute error of 3.36 and 4.36 in the test sets for lung and ovary, respectively. These models achieved lower error rates when compared with established state-of-the-art tissue-agnostic methylation models, emphasizing the importance of a tissue-specific approach. Additionally, this work has shown how the application of Hierarchical Image Pyramid Transformers for feature extraction significantly enhances age modeling using histological images. Finally, we evaluated the benefits of integrating multiple data modalities into a single model. Combining methylation data with other data modalities only marginally improved performance likely due to the limited number of available samples. Combining gene expression with histological features yielded more accurate age predictions compared with the individual performance of these data types. Given these results, this study shows how machine learning applications can be extended to/in multi-modal aging research. Code used is available at https://github.com/zroger49/multi_modal_age_prediction.

Abstract
APAtizer is a tool designed to analyze alternative polyadenylation events on RNA-sequencing data. The tool handles different file formats, including BAM, htseq, and DaPars bedGraph files. It provides a user-friendly interface that allows users to generate informative visualizations, including Volcano plots, heatmaps, and gene lists. These outputs allow the user to retrieve useful biological insights such as the occurrence of polyadenylation events when comparing two biological conditions. In addition, it can perform differential gene expression, gene ontology analysis, visualization of Venn diagram intersections, and correlation analysis.