A review: simulation tools for genome-wide interaction studies.

Genome-wide association study (GWAS) is essential for investigating the genetic basis of complex diseases; nevertheless, it usually ignores the interaction of multiple single nucleotide polymorphisms (SNPs). Genome-wide interaction studies provide crucial means for exploring complex genetic interactions that GWAS may miss. Although many interaction methods have been proposed, challenges still persist, including the lack of epistasis models and the inconsistency of benchmark datasets. SNP data simulation is a pivotal intermediary between interaction methods and real applications. Therefore, it is important to obtain epistasis models and benchmark datasets by simulation tools, which is helpful for further improving interaction methods. At present, many simulation tools have been widely employed in the field of population genetics. According to their basic principles, these existing tools can be divided into four categories: coalescent simulation, forward-time simulation, resampling simulation, and other simulation frameworks. In this paper, their basic principles and representative simulation tools are compared and analyzed in detail. Additionally, this paper provides a discussion and summary of the advantages and disadvantages of these frameworks and tools, offering technical insights for the design of new methods, and serving as valuable reference tools for researchers to comprehensively understand GWAS and genome-wide interaction studies.

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study.

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.