The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Friday, August 12 until 2:00 AM ET on Saturday, August 13 due to maintenance. We apologize for the inconvenience.
Explore Scholarly Publications and Datasets in the NSF-PAR
Have feedback or suggestions for a way to improve these results?
!
Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher.
Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?
Some links on this page may take you to non-federal websites. Their policies may differ from this site.
Abstract 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 »synthetic lethal relationships. These models then identify unexpected sets of 100-300 genes where reduced CRISPR measurements can produce genome-scale loss-of-function predictions across >18,000 genes. Thus, it is possible to reduce in vitro CRISPR libraries by orders of magnitude—with some information loss—when we remove redundant genes and not redundant sgRNAs.« less
Free, publicly-accessible full text available December 1, 2023
Tran, Thu Nguyen-Anh; Wikle, Nathan B.; Albert, Emmy; Inam, Haider; Strong, Emily; Brinda, Karel; Leighow, Scott M.; Yang, Fuhan; Hossain, Sajid; Pritchard, Justin R.; et al(
, BMC Medicine)
Abstract 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 »on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not have been included in the first round of vaccination. And, we account for age-specific immune patterns in both states at the time of the start of the vaccination program. Our analysis assumes that health systems during winter 2020–2021 had equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff. Results We find that allocating a substantial proportion (>75 % ) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. This result is robust to different profiles of waning vaccine efficacy and several different assumptions on age mixing during and after lockdown periods. As we do not explicitly model other high-mortality groups, our results on vaccine allocation apply to all groups at high risk of mortality if infected. A median of 327 to 340 deaths can be avoided in Rhode Island (3444 to 3647 in Massachusetts) by optimizing vaccine allocation and vaccinating the elderly first. The vaccination campaigns are expected to save a median of 639 to 664 lives in Rhode Island and 6278 to 6618 lives in Massachusetts in the first half of 2021 when compared to a scenario with no vaccine. A policy of vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and would result in 0.5% to 1% reductions in cumulative hospitalizations and deaths by mid-2021. Conclusions Assuming high vaccination coverage (>28 % ) and no major changes in distancing, masking, gathering size, hygiene guidelines, and virus transmissibility between 1 January 2021 and 1 July 2021 a combination of vaccination and population immunity may lead to low or near-zero transmission levels by the second quarter of 2021.« less
Free, publicly-accessible full text available December 1, 2022
