A comparative benchmarking and evaluation framework for heterogeneous network-based drug repositioning methods.

Computational drug repositioning, which involves identifying new indications for existing drugs, is an increasingly attractive research area due to its advantages in reducing both overall cost and development time. As a result, a growing number of computational drug repositioning methods have emerged. Heterogeneous network-based drug repositioning methods have been shown to outperform other approaches. However, there is a dearth of systematic evaluation studies of these methods, encompassing performance, scalability and usability, as well as a standardized process for evaluating new methods. Additionally, previous studies have only compared several methods, with conflicting results. In this context, we conducted a systematic benchmarking study of 28 heterogeneous network-based drug repositioning methods on 11 existing datasets. We developed a comprehensive framework to evaluate their performance, scalability and usability. Our study revealed that methods such as HGIMC, ITRPCA and BNNR exhibit the best overall performance, as they rely on matrix completion or factorization. HINGRL, MLMC, ITRPCA and HGIMC demonstrate the best performance, while NMFDR, GROBMC and SCPMF display superior scalability. For usability, HGIMC, DRHGCN and BNNR are the top performers. Building on these findings, we developed an online tool called HN-DREP (http://hn-drep.lyhbio.com/) to facilitate researchers in viewing all the detailed evaluation results and selecting the appropriate method. HN-DREP also provides an external drug repositioning prediction service for a specific disease or drug by integrating predictions from all methods. Furthermore, we have released a Snakemake workflow named HN-DRES (https://github.com/lyhbio/HN-DRES) to facilitate benchmarking and support the extension of new methods into the field.

Bi-functionality of glyoxal caged nucleic acid coupled with CRISPR/Cas12a system for Hg2+ determination.

A highly sensitive and selective fluorescence method has been conducted for the detection of Hg2+ based on aminophenylboronic acid-modified carboxyl magnetic beads (CMB@APBA) and CRISPR/Cas12a system mediated by glyoxal caged nucleic acid (gcDNA). As a bi-functional DNA linker, gcDNA offers advantages of simultaneous recognition by boronic acid and complementary DNA/RNA. Under acidic condition, gcDNA can be immobilized on CMB@APBA through the formation of borate ester bond. The formed boric acid-esterified gcDNA can further bind with complementary CRISPR RNA through A-T base pairing to activate Cas12a with kcat/Km ratio of 3.4 × 107 s-1 M-1, allowing for amplified signal. Hg2+ can specifically combine with CMB@APBA, resulting in the release of gcDNA from CMB@APBA and the following inhibition on the activation of CRISPR/Cas12a system around magnetic bead. Under optimal conditions, the method exhibits a linear range from 20 to 250 nM, with a detection limit of 2.72 nM. The proposed method can detect Hg2+ in milk and tea beverages, providing a great significance for on-site monitoring of Hg2+ contamination in food.

Genome-wide screening for highly discriminative SNPs for personal identification and their assessment in world populations.

The applications of DNA profiling aim to identify perpetrators, missing family members and disaster victims in forensic investigations. Single nucleotide polymorphisms (SNPs) based forensic applications are emerging rapidly with a potential to replace short tandem repeats (STRs) based panels which are now being used widely, and there is a need for a well-designed SNP panel to meet such challenge for this transition. Here we present a panel of 175 SNP markers (referred to as Fudan ID Panel or FID), selected from ∼3.6 million SNPs, for the application of personal identification. We optimized and validated FID panel using 729 Chinese individuals using a next generation sequencing (NGS) technology. We showed that the SNPs in the panel possess very high heterozygosity as well as low within- and among-continent differentiations, enabling FID panel exhibit discrimination power in both regional and worldwide populations, with the average match probabilities ranging from 4.77×10-71 to 1.06×10-64 across 54 world populations. With the advent of biomedical research, the SNPs connecting physical anthropological, physiological, behavioral and phenotypic traits will be eventually added to the forensic panels that will revolutionize criminal investigation.