Machine learning-based prediction models to guide the selection of Cas9 variants for efficient gene editing.

The increasing emergence of Cas9 variants has attracted broad interest, as these variants were designed to expand CRISPR applications. New Cas9 variants typically feature higher editing efficiency, improved editing specificity, or alternative PAM sequences. To select Cas9 variants and gRNAs for high-fidelity and efficient genome editing, it is crucial to systematically quantify the editing performances of gRNAs and develop prediction models based on high-quality datasets. Using synthetic gRNA-target paired libraries and next-generation sequencing, we compared the activity and specificity of gRNAs of four SpCas9 variants. The nucleotide composition in the PAM-distal region had more influence on the editing efficiency of HiFi Cas9 and LZ3 Cas9. We further developed machine learning models to predict the gRNA efficiency and specificity for the four Cas9 variants. To aid users from broad research areas, the machine learning models for the predictions of gRNA editing efficiency within human genome sites are available on our website.

Self-Regulation Failure? The Influence Mechanism of Leader Reward Omission on Employee Deviant Behavior.

Contingent reinforcement behavior is generally regarded as one of the key elements of being a "good" leader, yet the question of what happens when this behavior is absent has received little attention in past empirical research. Drawing upon self-regulation theory, we develop and test a model that specifies the effects of leader reward omission on employes' deviant behavior. Using the data of 230 workers from two manufacturing companies located in South China collected across three time points, we find that leader reward omission is positively associated with deviant behavior. Moreover, the indirect effects of leader reward omission on employes' deviant behavior are mediated by moral disengagement. Our study also reveals that Machiavellianism can aggravate the positive effect of leader reward omission on moral disengagement, and subsequently exacerbate the indirect effect on employes' deviant behavior. Taken together, our findings reveal the consequences of leader reward omission, and the importance of examining subordinate self-regulation under the lack of positive reinforcement.