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A pan-CRISPR analysis of mammalian cell specificity identifies ultra-compact sgRNA subsets for genome-scale experimentsAbstract A genetic knockout can be lethal to one human cell type while increasing growth rate in another. This context specificity confounds genetic analysis and prevents reproducible genome engineering. Genome-wide CRISPR compendia across most common human cell lines offer the largest opportunity to understand the biology of cell specificity. The prevailing viewpoint, synthetic lethality, occurs when a genetic alteration creates a unique CRISPR dependency. Here, we use machine learning for an unbiased investigation of cell type specificity. Quantifying model accuracy, we find that most cell type specific phenotypes are predicted by the function of related genes of wild-type sequence, notmore »Free, publicly-accessible full text available December 1, 2023
Free, publicly-accessible full text available May 2, 2023
SARS-CoV-2 epidemic after social and economic reopening in three U.S. states reveals shifts in age structure and clinical characteristicsCOVID-19 clinical outcomes improved over the first 6 months, but infection fatality rates were initially above 1.5%.Free, publicly-accessible full text available January 28, 2023
Optimal SARS-CoV-2 vaccine allocation using real-time attack-rate estimates in Rhode Island and MassachusettsAbstract Background When three SARS-CoV-2 vaccines came to market in Europe and North America in the winter of 2020–2021, distribution networks were in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation was critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs likely require that distribution is prioritized to the elderly, health care workers, teachers, essential workers, and individuals with comorbidities putting them at risk of severe clinical progression. Methods We evaluate various age-based vaccine distributions using a validated mathematical model basedmore »Free, publicly-accessible full text available December 1, 2022