VCFshiny: an R/Shiny application for interactively analyzing and visualizing genetic variants.

Summary: Next-generation sequencing generates variants that are typically documented in variant call format (VCF) files. However, comprehensively examining variant information from VCF files can pose a significant challenge for researchers lacking bioinformatics and programming expertise. To address this issue, we introduce VCFshiny, an R package that features a user-friendly web interface enabling interactive annotation, interpretation, and visualization of variant information stored in VCF files. VCFshiny offers two annotation methods, Annovar and VariantAnnotation, to add annotations such as genes or functional impact. Annotated VCF files are deemed acceptable inputs for the purpose of summarizing and visualizing variant information. This includes the total number of variants, overlaps across sample replicates, base alterations of single nucleotides, length distributions of insertions and deletions (indels), high-frequency mutated genes, variant distribution in the genome and of genome features, variants in cancer driver genes, and cancer mutational signatures. VCFshiny serves to enhance the intelligibility of VCF files by offering an interactive web interface for analysis and visualization. Availability and implementation: The source code is available under an MIT open source license at https://github.com/123xiaochen/VCFshiny with documentation at https://123xiaochen.github.io/VCFshiny.

Generation of hiPSCs with ABO c.767T>C substitution: resulting in splicing variants.

Introduction: The ABO blood group system has important clinical significance in the safety of blood transfusion and organ transplantation. Numerous ABO variations, especially variations in the splice sites, have been identified to be associated with some ABO subtypes. Methods: Here, we performed the c.767T>C substitution of the ABO gene in human induced pluripotent stem cells (hiPSCs) by the adenosine base editor (ABE) system and described its characteristics at the genome level in detail. Results: The hiPS cell line with c.767T>C substitution maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers in vivo. The genome-wide analysis demonstrated that the c.767T>C substitution in the ABO gene did not cause any detected negative effect in hiPSCs at the genome level. The splicing transcript analysis revealed that splicing variants were observed in the hiPSCs with ABO c.767T>C substitutions. Conclusion: All these results indicated that some splicing variants occurred in hiPSCs with c.767 T>C substitution of ABO gene, which probably had a significant effect on the formation of the rare ABO*Ael05/B101 subtype.

Generation of a homozygous ARHGAP11B knockout hiPSC line by CRISPR/Cas9 system.

The human specific gene ARHGAP11B is preferentially expressed in neural progenitors of fetal neocortex and plays a key role in the evolutionary expansion of the neocortex. Here, we generated a homozygous ARHGAP11B knockout human induced pluripotent stem cell (hiPSC) line through CRISPR/Cas9 gene editing system. ARHGAP11B deficient cell line maintained a normal karyotype (46, XX), expressed pluripotency markers, and showed the capability to spontaneously differentiate into all three germ layers in vivo. The ARHGAP11B knockout cell line can provide a new cell model for studying the evolution of human neocortex.