Understanding how complex networks of genes integrate to produce dividing cells is an important goal that is limited by the difficulty in defining the function of individual genes. Current resources for the systematic identification of gene function such as siRNA libraries and collections of deletion strains are costly and organism specific. We describe here integration profiling, a novel approach to identify the function of eukaryotic genes based upon dense maps of transposon integration. As a proof of concept, we used the transposon Hermes to generate a library of 360,513 insertions in the genome of Schizosaccharomyces pombe. On average, we obtained one insertion for every 29 bp of the genome. Hermes integrated more often into nucleosome free sites and 33% of the insertions occurred in ORFs. We found that ORFs with low integration densities successfully identified the genes that are essential for cell division. Importantly, the nonessential ORFs with intermediate levels of insertion correlated with the nonessential genes that have functions required for colonies to reach full size. This finding indicates that integration profiles can measure the contribution of nonessential genes to cell division. While integration profiling succeeded in identifying genes necessary for propagation, it also has the potential to identify genes important for many other functions such as DNA repair, stress response, and meiosis.T HE accelerated rate of gene discovery in an increasing number of species has challenged the existing methods for determining the functions of genes. Traditional approaches for characterizing the function of genes rely on obtaining mutant alleles and testing them in individual experiments for phenotypes. Direct and systematic methods for evaluating gene function have been developed. Genomewide RNAi screens of cultured cells require the synthesis, validation, and refinement of large libraries of double stranded RNAs or vectors that express double stranded RNAs. While RNAi screens have successfully identified many genes that may contribute to key functions such as the replication of human immunodeficiency virus (Brass et al. 2008;Konig et al. 2008;Zhou et al. 2008), the production of RNAi libraries is resource intensive and substantial complications exist, such as off-target effects and incomplete mRNA knockdown.An alternate approach for characterizing gene function in haploid cells relies on targeted gene deletions. For Saccharomyces cerevisiae and Schizosaccharomyces pombe, collections of strains have been created that contain systematic deletions of the predicted coding sequences (Winzeler et al. 1999;Kim et al. 2010). These comprehensive collections of strains can be readily screened under a variety of conditions to probe the contributions of individual genes to specific processes. However, considerable effort and resources are required to generate deletion sets and once generated, it is difficult to study the deletions in combination with other mutations. Another limitation with deletion collec...

Declaration of interests KNA serves on the scientific advisory board of TrioHealth, Inc.. MJG has served as an ad hoc member of Canadian HIV Advisory Boards of Merck, Gilead and ViiV. RDM has previously consulted for Medscape. MJS has received grants from Gilead and, formerly, Merck. The remaining authors have no conflicts of interest to disclose.

Key Points Question Are the rate and risk of COVID-19 breakthrough infections higher among vaccinated people with vs without HIV in the United States through December 31, 2021? Findings In this cohort study of 113 994 patients, risk of breakthrough infection was low overall (3.8%) but 28% higher in people with vs without HIV. The breakthrough rate was also higher in people with vs without HIV (55 cases per 1000 person-years vs 43 cases per 1000 person-years). Meaning The higher rate and risk of infection in people with HIV observed in this study suggests comprehensive inclusion of this population in recommendations for additional primary doses in immunocompromised groups.

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Diseases were associated with socioeconomic status and age of patients and with serotype of organism.

One in 10 and 1 in 50 syphilis or gonorrhea diagnoses were followed by an human immunodeficiency virus diagnosis within 2 years among men who have sex with men and non–men who have sex with men males, respectively, in Baltimore City.

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004–2007, 2008–2011, and 2012–2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004–2007 to 2012–2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities.