Identification of causal genes for complex traits.

MotivationAlthough genome-wide association studies (GWAS) have identified thousands of variants associated with common diseases and complex traits, only a handful of these variants are validated to be causal. We consider 'causal variants' as variants which are responsible for the association signal at a locus. As opposed to association studies that benefit from linkage disequilibrium (LD), the main challenge in identifying causal variants at associated loci lies in distinguishing among the many closely correlated variants due to LD. This is particularly important for model organisms such as inbred mice, where LD extends much further than in human populations, resulting in large stretches of the genome with significantly associated variants. Furthermore, these model organisms are highly structured and require correction for population structure to remove potential spurious associations.ResultsIn this work, we propose CAVIAR-Gene (CAusal Variants Identification in Associated Regions), a novel method that is able to operate across large LD regions of the genome while also correcting for population structure. A key feature of our approach is that it provides as output a minimally sized set of genes that captures the genes which harbor causal variants with probability ρ. Through extensive simulations, we demonstrate that our method not only speeds up computation, but also have an average of 10% higher recall rate compared with the existing approaches. We validate our method using a real mouse high-density lipoprotein data (HDL) and show that CAVIAR-Gene is able to identify Apoa2 (a gene known to harbor causal variants for HDL), while reducing the number of genes that need to be tested for functionality by a factor of 2.Availability and implementationSoftware is freely available for download at genetics.cs.ucla.edu/caviar

Internet diffusion and interregional digital divide in Russia: trends, factors, and the influence of the pandemic

The demand for digital technologies has been growing due to a shift in the technological and economic paradigm. The need for online services has increased since the beginning of the COVID pandemic. There are significant disparities between Russian regions in the digital technology accessibility and the development of computer skills. In 2020, the Internet diffused rapidly in most regions, although previously, there had been a slowdown. As markets got saturated with digital services, the digital divide between Russian regions narrowed. Overall, the Internet use patterns are consistent with those of the spatial diffusion of innovations. Amongst the leaders, there are regions home to the largest agglomerations and northern territories of Russia, whereas those having a high proportion of rural population lag behind. Coastal and border regions (St. Petersburg, the Kaliningrad region, Karelia, Primorsky Krai, etc.) have better access to the Internet due to their proximity to the centres of technological innovations as well as the high intensity of external relations. Leading regions have an impact on their neighbours through spatial diffusion. Econometrically, access to the Internet depends on income, the average age and level of education, and its use depends on the business climate and Internet accessibility factors. Regional markets are gradually getting more saturated with digital services and technologies. The difference between regions in terms of access to the Internet is twofold, whereas, in terms of digital technology use, the gap is manifold. In many regions, the share of online commerce, which became the driver of economic development during the lockdown, is minimal. Based on the results of the study, several recommendations have been formulated

Integrating Functional Data to Prioritize Causal Variants in Statistical Fine-Mapping Studies

Standard statistical approaches for prioritization of variants for functional testing in fine-mapping studies either use marginal association statistics or estimate posterior probabilities for variants to be causal under simplifying assumptions. Here, we present a probabilistic framework that integrates association strength with functional genomic annotation data to improve accuracy in selecting plausible causal variants for functional validation. A key feature of our approach is that it empirically estimates the contribution of each functional annotation to the trait of interest directly from summary association statistics while allowing for multiple causal variants at any risk locus. We devise efficient algorithms that estimate the parameters of our model across all risk loci to further increase performance. Using simulations starting from the 1000 Genomes data, we find that our framework consistently outperforms the current state-of-the-art fine-mapping methods, reducing the number of variants that need to be selected to capture 90% of the causal variants from an average of 13.3 to 10.4 SNPs per locus (as compared to the next-best performing strategy). Furthermore, we introduce a cost-to-benefit optimization framework for determining the number of variants to be followed up in functional assays and assess its performance using real and simulation data. We validate our findings using a large scale meta-analysis of four blood lipids traits and find that the relative probability for causality is increased for variants in exons and transcription start sites and decreased in repressed genomic regions at the risk loci of these traits. Using these highly predictive, trait-specific functional annotations, we estimate causality probabilities across all traits and variants, reducing the size of the 90% confidence set from an average of 17.5 to 13.5 variants per locus in this data

simGWAS: a fast method for simulation of large scale case-control GWAS summary statistics.

MOTIVATION: Methods for analysis of GWAS summary statistics have encouraged data sharing and democratized the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some 'truth' is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study. RESULTS: We have developed a novel method based on an alternative approach, directly simulating GWAS summary data, without individual data as an intermediate step. We mathematically derive the expected statistics for any set of causal variants and their effect sizes, conditional upon control haplotype frequencies (available from public reference datasets). Simulation of GWAS summary output can be conducted independently of sample size by simulating random variates about these expected values. Across a range of scenarios, our method, produces very similar output to that from simulating individual genotypes with a substantial gain in speed even for modest sample sizes. Fast simulation of GWAS summary statistics will enable more complete and rapid evaluation of summary statistic methods as well as opening new potential avenues of research in fine mapping and gene set enrichment analysis. AVAILABILITY AND IMPLEMENTATION: Our method is available under a GPL license as an R package from http://github.com/chr1swallace/simGWAS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Технико-экономические подходы к вопросу уменьшения энергозатрат в отдельных отраслях Белкоопсоюза

The paper considers an approach to execution of measures pertaining to higher power efficiency in some branches of consumers’ cooperation of theRepublicofBelarus. The approach is based on the method for unification of the investigated enterprises. The described mechanism takes into account organizational peculiarities of the Belkoopsoyuz structure and also technical equipment of the investigated consumers’ cooperation and it permits to specify the most power consuming directions and develop typical innovation technical solutions pertaining to the objects of the consumers’ cooperation of theRepublicofBelarus.Рассматривается подход к проведению мероприятий по повышению энергетической эффективности в отдельных отраслях потребительской кооперации Республики Беларусь, основанный на методе унификации исследуемых предприятий. Описываемый механизм учитывает как организационные особенности структуры Белкоопсоюза, так и техническую оснащенность исследуемых отраслей потребительской кооперации, позволяет выделить наиболее энергоемкие направления и разработать типовые инновационные технические решения по объектам потребительской кооперации Республики Беларусь

Анализ энергетических затрат на технологию производства хлебобулочных изделий в потребительской кооперации Республики Беларусь

Results of a numerical analysis of power efficiency in usage of fuel- and power resources in bakery sub-industry of the consumer cooperation in the Republic of Belarus are given in the paper.  The paper reveals economic justification of executing technological modernization of bakery plants with installation of energy-efficient equipment.Приведены результаты численного анализа энергетической эффективности использования топливно-энергетических ресурсов в хлебопекарной подотрасли потребительской кооперации Республики Беларусь. Показана экономическая целесообразность проведения технологической модернизации хлебозаводов с установкой энергоэффективного оборудования.