SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis

Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two single-cell CRISPR screens how these challenges cause calibration issues. We propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling, which infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCEPTRE demonstrates very good calibration and sensitivity on CRISPR screen data, yielding hundreds of new regulatory relationships supported by orthogonal biological evidence.

COMPARATIVE CHARACTERISTICS OF MODELS OF STATE SUPPORT FOR NATIONAL ECONOMIES OF THE WORLD IN THE CONTEXT OF THE COVID-19 PANDEMIC

The article describes economic and social problems of different countries resulting from the spread of the COVID-19 pandemic. The paper defines general and specific characteristics of economic difficulties in developed and developing countries. The authors carry out a preliminary analysis of the economic and social consequences of the coronavirus pandemic for the global economy as a whole. The study presents a comparative description of approaches to the formation of state financial support for businesses and households in developed countries of the European Union, China and Russia. The article identifies two main models of state support – push/pull, shows their differences in the amount of funds, the breadth of coverage of final recipients, the availability of benefits, and the degree of bureaucratization of procedures. The paper reveals the rules and procedures for providing state events to support businesses and entrepreneurs on the Russian market, and also uncovers shortcomings that significantly affected the economic situation of agents. The authors describe the consequences of lockdown for the economies of various countries. The study conducts a screen analysis of health systems and their mobilization response to the spread of coronavirus infection. The paper draws conclusions about the advantages of proactive social support for the population and business, the need to increase its targeting and the spread of effective practices in the future.

Conditional resampling improves calibration and sensitivity in single-cell CRISPR screen analysis

Single-cell CRISPR screens are an emerging biotechnology promising unprecedented insights into gene regulation. However, the analysis of these screens presents significant statistical challenges. For example, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two recent large-scale single-cell CRISPR screens how these challenges cause calibration issues among existing analysis methods. To address these challenges, we propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling. This methodology, designed to avoid calibration issues due to technical confounders and expression model misspecification, infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCETPRE demonstrates excellent calibration and sensitivity on the CRISPR screen data and yields 200 new regulatory relationships, many of which are supported by existing functional data.

CASPR, an analysis pipeline for single and paired guide RNA CRISPR screens, reveals optimal target selection for long noncoding RNAs

Motivation CRISPR-Cas9 loss-of-function pooled screening promises to identify which long noncoding RNAs (lncRNAs), amongst the many thousands to have been annotated so far, are capable of mediating cellular functions. The two principal loss-of-function perturbations, CRISPR-inhibition and CRISPR-deletion, employ one and two guide RNAs, respectively. However, no software solution has the versatility to identify hits across both modalities, and the optimal design parameters for such screens remain poorly understood. Results Here we present CASPR (CRISPR Analysis for Single and Paired RNA-guides), a user-friendly, end-to-end screen analysis tool. CASPR is compatible with both CRISPRi and CRISPR-del screens, and balances sensitivity and specificity by generating consensus predictions from multiple algorithms. Benchmarking on ground-truth sets of cancer-associated lncRNAs demonstrates CASPR’s improved sensitivity with respect to existing methods. Applying CASPR to published screens, we identify two parameters that predict lncRNA hits: expression, and annotation quality of the transcription start site. Thus CASPR is a versatile and complete solution for lncRNA CRISPR screen analysis, and reveals principles for including lncRNAs in screening libraries. Availability https://judithbergada.github.io/CASPR/ Supplementary information Supplementary data are available at Bioinformatics online.