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Single-cell genomics has enabled the study of biological processes at an unprecedented scale and resolution. These studies were enabled by innovative data generation technologies coupled with emerging computational tools specialized for single-cell data. As single-cell technologies have become more prevalent, so has the development of new analysis tools, which has resulted in over 1,700 published algorithms1 (as of February 2024). Thus, there is an increasing need to continually evaluate which algorithm performs best in which context to inform best practices2,3 that evolve with the field. In many fields of quantitative science, public competitions and benchmarks address this need by evaluating state-of-the-art methods against known criteria, following the concept of a common task framework4. Here, we present Open Problems, a living, extensive, community-guided platform including 12 current single-cell tasks that we envisage raising standards for the selection, evaluation and development of methods in single-cell analysis. 

Abstract Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.