Cutting-edge research employing single-cell RNA sequencing and multi-omics is elucidating complex disease mechanisms and identifying novel biomarkers across multiple conditions. Studies have detailed cellular pathways in post-traumatic stress disorder and depression by examining gene expression in specific brain cells, highlighted distinct immune cell populations driving the heterogeneity of systemic sclerosis organ damage, and mapped cellular origins of liver transplant injury through cfDNA methylation patterns. Integrative exome sequencing combined with machine learning further identifies novel genes contributing to systemic sclerosis risk. These advances pave the way for precision diagnostics and tailored therapies for autoimmune, psychiatric, and transplant-related diseases.