Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.

Copy number alterations are driving forces of tumour development and the emergence of intratumour heterogeneity. A comprehensive picture of these genomic aberrations is therefore essential for the development of personalised and precise cancer diagnostics and therapies. Single-cell sequencing offers the highest resolution for copy number profiling down to the level of individual cells. Recent high-throughput protocols allow for the processing of hundreds of cells through shallow whole-genome DNA sequencing. The resulting low read-depth data poses substantial statistical and computational challenges to the identification of copy number alterations. We developed SCICoNE, a statistical model and MCMC algorithm tailored to single-cell copy number profiling from shallow whole-genome DNA sequencing data. SCICoNE reconstructs the history of copy number events in the tumour and uses these evolutionary relationships to identify the copy number profiles of the individual cells. We show the accuracy of this approach in evaluations on simulated data and demonstrate its practicability in applications to a xenograft breast cancer sample. * Contributed equally

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient’s data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe.

Understanding the structure of the heart at the microscopic scale of cardiomyocytes and their aggregates provides new insights into the mechanisms of heart disease and enables the investigation of effective therapeutics. Diffusion Tensor Cardiac Magnetic Resonance (DT-CMR) is a unique non-invasive technique that can resolve the microscopic structure, organisation, and integrity of the myocardium without the need for exogenous contrast agents. However, this technique suffers from relatively low signal-to-noise ratio (SNR) and frequent signal loss due to respiratory and cardiac motion. Current DT-CMR techniques rely on acquiring and averaging multiple signal acquisitions to improve the SNR. Moreover, in order to mitigate the influence of respiratory movement, patients are required to perform many breath holds which results in prolonged acquisition durations (e.g., ∼30 mins using the existing technology). In this study, we propose a novel cascaded Convolutional Neural Networks (CNN) based compressive sensing (CS) technique and explore its applicability to improve DT-CMR acquisitions. Our simulation based studies have achieved high reconstruction fidelity and good agreement between DT-CMR parameters obtained with the proposed reconstruction and fully sampled ground truth. When compared to other stateof-the-art methods, our proposed deep cascaded CNN method and its stochastic variation demonstrated significant improvements. To the best of our knowledge, this is the first study using deep CNN based CS for the DT-CMR reconstruction. In addition, with relatively straightforward modifications to the acquisition scheme, our method can easily be translated into a method for online, at-the-scanner reconstruction enabling the deployment of accelerated DT-CMR in various clinical applications.