Identification of druggable genes for multiple myeloma based on genomic information.

Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.

Investigation of susceptibility genes for chickenpox disease across multiple continents.

Chickenpox (varicella) is caused by infection with the varicella-zoster virus (VZV), a neurotropic alpha herpes virus with a double-stranded DNA genome. Chickenpox can cause life-threatening complications, including subsequent bacterial infections, central nervous system symptoms, and even death without any risk factors. Few studies have been reported to investigate genetic susceptibility implicated in chickenpox. Herein, our study identified global genetic variants that potentially contributed to chickenpox susceptibility by utilizing the established bioinformatic-based approach. We integrated several databases, such as genome-wide association studies (GWAS) catalog, GTEx portal, HaploReg version 4.1, and Ensembl databases analyses to investigate susceptibility genes associated with chickenpox. Notably, increased expression of HLA-S, HCG4P5, and ABHD16A genes underlie enhanced chickenpox susceptibility in the European, American, and African populations. As compared to the Asian population, Europeans, Americans, and Africans have higher allele frequencies of the extant variants rs9266089, rs10947050, and rs79501286 from the susceptibility genes. Our study suggested that these susceptibility genes and associated genetic variants might play a critical role in chickenpox progression based on host genetics with clinical implications.