Fig. 1

Phenotype-based high-throughput laser-aided isolation and sequencing (PHLI-seq) bridges the genotypic information to the corresponding phenotypic one in high throughput. a The tumor mass is sectioned and stained with H&E. The section is prepared on a discharging layer-coated glass. The tissue section is imaged, and the cancer cells in the section are grouped. Using grouping by phenotypes, cells that represent minor populations can be chosen. Grouping can be aided by pathologist manual observations. b A tissue section or cells prepared on the discharging layer can be isolated with an infrared (1064 nm) laser. Because the discharging layer readily vaporizes where the infrared laser is applied, the cells on the vaporized area can be released downward by pressure due to vaporization. c After isolating the cells, we performed whole-genome amplification and massively parallel sequencing to analyze the CNA and SNV with their spatial organization in the tissue context. d PHLI-seq can be applied to various types of samples, and the resolution of isolating cells can be down to single-cell level