Clinical Genomic Analysis and Diagnosis --Genomic Analysis Ex Vivo, in Vitro and in Silico.

Seven years ago, I systemically reviewed single cell techniques with genomic and proteomic analyses which was called Single-Cell Genomic Analysis. After many years of arduous work, single cell techniques with downstream genomic and proteomic analysis have been applied to clinical fields including molecular pathology, molecular genetics, forensic medicine and biomarker discovery. On top of that, dynamic cell-sorting technique combined with downstream cell culture and genomic analysis of stem cell for regeneration medicine and cancer stem cell for differentiation have also been greatly developed in clinical fields. More importantly, tissue level sampling with in silico analysis has been applied in therapeutic targeting for advanced neoplastic disease. Recent development in sorting homogeneous cells in vitro (or single cells technique), ex vivo (dynamic analysis or small number of cell culture with downstream genomic analysis) and insilico (tissue level sampling with in silico analysis) have allowed physician scientists with a choice to select one of these above techniques with genomic analysis to apply to their clinical research fields. To fully understand these modern techniques, this manual will review recently developed methods or clinical genomic analysis in vitro, in silico and ex vivo. In the review paper, I will also introduce how to utilize these techniques in different clinical fields. The manual will also address some of the challenges for clinical genomics analysis and diagnosis due to mixed cells from clinical specimens.