J. G. González

Melanie F. Pradier, Niranjani Prasad, Paidamoyo Chapfuwa et al. · microsoft-research

Recent advances in immunomics have shown that T-cell receptor (TCR) signatures can accurately predict active or recent infection by leveraging the high specificity of TCR binding to disease antigens. However, the extreme diversity of the adaptive immune repertoire presents challenges in reliably identifying disease-specific TCRs. Population genetics and sequencing depth can also have strong systematic effects on repertoires, which requires careful consideration when developing diagnostic models. We present an Adaptive Immune Repertoire-Invariant Variational Autoencoder (AIRIVA), a generative model that learns a low-dimensional, interpretable, and compositional representation of TCR repertoires to disentangle such systematic effects in repertoires. We apply AIRIVA to two infectious disease case-studies: COVID-19 (natural infection and vaccination) and the Herpes Simplex Virus (HSV-1 and HSV-2), and empirically show that we can disentangle the individual disease signals. We further demonstrate AIRIVA's capability to: learn from unlabelled samples; generate in-silico TCR repertoires by intervening on the latent factors; and identify disease-associated TCRs validated using TCR annotations from external assay data.

Javier G. Gonzalez

The Offline software framework for data analysis of the Pierre Auger Observatory is a set of computational tools developed to cater to the needs of a large and geographically dispersed collaboration established to measure the spectrum, arrival directions, and composition of ultra-high energy cosmic rays over a period of 20 years. One of its design goals was to facilitate the collaborative effort by allowing collaborators to progressively contribute small portions of code. The observatory has grown over time and it has undergone improvements and additions that have tested the flexibility of the framework. The framework was originally thought to accommodate a hybrid view of cosmic ray detection, made of a surface and a fluorescence detector. Since then, the framework has been extended to include a radio antenna array and both under-ground and above-ground scintillator arrays. Different tools from the framework have been used by other collaborations, notably NA61/Shine and HAWC. All these experiences accumulated over the years allow us to draw conclusions in terms of the successes and failures of the original design.