Gabriele Scalia

Charting an organs' biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. Tangram can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.

Advances in deep neural network (DNN)-based molecular property prediction have recently led to the development of models of remarkable accuracy and generalization ability, with graph convolutional neural networks (GCNNs) reporting state-of-the-art performance for this task. However, some challenges remain, and one of the most important that needs to be fully addressed concerns uncertainty quantification. DNN performance is affected by the volume and the quality of the training samples. Therefore, establishing when and to what extent a prediction can be considered reliable is just as important as outputting accurate predictions, especially when out-of-domain molecules are targeted. Recently, several methods to account for uncertainty in DNNs have been proposed, most of which are based on approximate Bayesian inference. Among these, only a few scale to the large data sets required in applications. Evaluating and comparing these methods has recently attracted great interest, but results are generally fragmented and absent for molecular property prediction. In this paper, we quantitatively compare scalable techniques for uncertainty estimation in GCNNs. We introduce a set of quantitative criteria to capture different uncertainty aspects and then use these criteria to compare MC-dropout, Deep Ensembles, and bootstrapping, both theoretically in a unified framework that separates aleatoric/epistemic uncertainty and experimentally on public data sets. Our experiments quantify the performance of the different uncertainty estimation methods and their impact on uncertainty-related error reduction. Our findings indicate that Deep Ensembles and bootstrapping consistently outperform MC-dropout, with different context-specific pros and cons. Our analysis leads to a better understanding of the role of aleatoric/epistemic uncertainty, also in relation to the target data set features, and highlights the challenge posed by out-of-domain uncertainty.

In the first hours of a disaster, up-to-date information about the area of interest is crucial for effective disaster management. However, due to the delay induced by collecting and analysing satellite imagery, disaster management systems like the Copernicus Emergency Management Service (EMS) are currently not able to provide information products until up to 48-72 h after a disaster event has occurred. While satellite imagery is still a valuable source for disaster management, information products can be improved through complementing them with user-generated data like social media posts or crowdsourced data. The advantage of these new kinds of data is that they are continuously produced in a timely fashion because users actively participate throughout an event and share related information. The research project Evolution of Emergency Copernicus services (E2mC) aims to integrate these novel data into a new EMS service component called Witness, which is presented in this paper. Like this, the timeliness and accuracy of geospatial information products provided to civil protection authorities can be improved through leveraging user-generated data. This paper sketches the developed system architecture, describes applicable scenarios and presents several preliminary case studies, providing evidence that the scientific and operational goals have been achieved.