Investigation of a 22-gene genomic classifier (GC) for risk stratification and molecular subtyping in an Asian prostate cancer (PCa) cohort.

249 Background: A 22-gene GC has been proposed to refine risk stratification of localized PCa by conventional NCCN criteria, and this may potentially influence treatment recommendations. Nonetheless, majority of studies looking at the utility of GC were conducted in White and non-White men from Western cohorts. We therefore investigated the association of GC with NCCN risk groups (RG) in an Asian PCa cohort. Additionally, we examined for inter-racial differences in molecular subtyping between Asian and White/non-White PCa. Methods: GC (Decipher Biosciences Inc., CA) was performed on diagnostic biopsies of men who were treated with radiotherapy +/- hormonal therapy at a single institution (N = 75). ISUP Gleason’s grade (GG) and tumor cellularity were reviewed by an expert GU pathologist. RNA was extracted from 2 x 2.0-mm tumor cores using Qiagen AllPrep DNA/RNA FFPE Kit (Qiagen, Germany) and gene expression was performed on Affymetrix Human Exon 1.0 ST Array (ThermoFischer, CA). PAM50 molecular subtyping was derived using the DecipherGRID database. Results: We profiled 80 tumors from 75 patients, comprising of 18 (24.0%), 9 (12.0%), 21 (28.0%), and 19 (25.3%) NCCN low-/favorable intermediate-, unfavorable intermediate-, high- and very high-RG, respectively; of note, 8 (10.7%) patients had regional/metastatic disease at diagnosis. Using the GC, 27 (33.8%), 14 (17.5%) and 39 (48.8%) were classified as low- (<0.45), intermediate- (0.45-0.6) and high-RG, respectively (>0.6). When stratified using a three-tier clinico-genomic (CG) classification system (Spratt et al. 2017), 6 of 21 (28.6%) NCCN-defined high-risk and 4 of 19 (21.1%) very high-risk patients were downgraded to CG-defined intermediate-/low-risk, while 2 of 27 (7.4%) NCCN low-/intermediate-risk patients were in fact upgraded to CG high-risk. Next, we interrogated the PAM50 basal-luminal signature in our cohort. Interestingly, when matched to White (N = 5762) and non-White (N = 155) for NCCN RG, ISUP GG and age, we observed a high proportion of basal subtype (62.7%) in Asians, which contrasted the prevalence observed in White (16.7%) and non-White (15.9%) North American patients (Chi-sq P <0.001). Conclusions: Here, we demonstrated the utility of the 22-gene GC for refining the NCCN risk stratification in a largest Asian PCa dataset to-date. An unexpectedly high proportion of PAM50 basal-subtype was observed, suggesting race-specific differences of the tumor transcriptome.

Design and Application of a Case Analysis System for Handling Power Grid Operational Accidents Based on Case-Based Reasoning

In recent years, power grid accidents have occurred frequently and higher requirements have been placed on their safety operation. In current safety management in the world, there is an effective practice that uses a unified standard for structuring an accident case database and based on that database, conducts quantitative analysis to cope with accident risks. However, that is not the case for power safety management. Case-based reasoning (CBR) is such a process that solves new problems based on the solutions to similar past problems. It works by matching a current problem with historical cases and solutions in a database, in order to obtain similar case solutions or inspirations. In the matching process, if necessary, such past solutions may be modified in order to better adapt to the current actual problems. Based on the CBR method, this paper proposes how to construct a case database of power grid operational accidents, provide data support for management of power grid risks and provide knowledge services for accurate grasping of grid accident development dynamics and making quick decisions to rapidly response to the emergencies. First, it designs an operational accident case database after considering the following three aspects: case features, power grid features and accident features based on safety management theory. Secondly, in terms of how to use the power grid operational accident case database, it proposed a two-level search strategy, as well as the corresponding similarity calculation methods for different feature attributes of the case. Finally, it carried out a demonstration to verify the model by selecting four typical grid accidents. The grid database and CBR strategy proposed in this article could help China’s power grids practice intelligent analysis of grid operational accidents and improve digitalization in safety management.

A Low-Altitude Flight Conflict Detection Algorithm Based on a Multilevel Grid Spatiotemporal Index

Flight conflict detection is fundamental to flight dispatch, trajectory planning, and flight safety control. An ever-increasing aircraft population and higher speeds, particularly the emergence of hypersonic/supersonic aircrafts, are challenging the timeliness and accuracy of flight conflict detection. Traditional trajectory conflict detection algorithms rely on traversing multivariate equations of every two trajectories, in order to yield the conflict result and involve extensive computation and high algorithmic complexity; these algorithms are often unable to provide the flight conflict solutions required quickly enough. In this paper, we present a novel, low-altitude flight conflict detection algorithm, based on the multi-level grid spatiotemporal index, that transforms the traditional trajectory-traversing multivariate conflict computation into a grid conflict state query of distributed grid databases. Essentially, this is a method of exchanging "storage space" for "computational time". First, we build the spatiotemporal subdivision and encoding model based on the airspace. The model describes the geometries of the trajectories, low-altitude obstacles, or dangerous fields and identifies the grid with grid codes. Next, we design a database table structure of the grid and create a grid database. Finally, we establish a multilevel grid spatiotemporal index, design a query optimization scheme, and examine the flight conflict detection results from the grid database. Experimental verification confirms that the computation efficiency of our algorithm is one order of magnitude higher than those of traditional methods. Our algorithm can perform real-time (dynamic/static) conflict detection on both individual aircraft and aircraft flying in formation with more efficient trajectory planning and airspace utilization.

grID: A CRISPR-Cas9 guide RNA Database and Resource for Genome-Editing

ABSTRACTCRISPR-Cas9 genome-editing is a revolutionary technology that is transforming biological research. The explosive growth and advances in CRISPR research over the last few years, coupled with the potential for clinical applications and therapeutics, is heralding a new era for genome engineering. To further support this technology platform and to provide a universal CRISPR annotation system, we introduce the grID database (http://crispr.technology), an extensive compilation of gRNA properties including sequence and variations, thermodynamic parameters, off-target analyses, and alternative PAM sites, among others. To aid in the design of optimal gRNAs, the website is integrated with other prominent databases, providing a wealth of additional resources to guide users from in silico analysis through experimental CRISPR targeting. Here, we make available all the tools, protocols, and plasmids that are needed for successful CRISPR-based genome targeting.