Chromosome-segment scanning for gain- or loss-of-function screening (CHASING)
Yan Xia,
Lichao Sun,
Zeyu Liang,
Zhongrao Han,
Jing Li,
Pengyu Dong,
Yi-Xin Huo,
Shuyuan Guo
Affiliations
Yan Xia
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
Lichao Sun
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China; Tangshan Research Institute, Beijing Institute of Technology, No. 57, South Jianshe Road, Lubei District, Tangshan, Hebei 063000, China
Zeyu Liang
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
Zhongrao Han
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
Jing Li
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
Pengyu Dong
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China
Yi-Xin Huo
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China; Tangshan Research Institute, Beijing Institute of Technology, No. 57, South Jianshe Road, Lubei District, Tangshan, Hebei 063000, China; Center for Future Foods, Muyuan Laboratory, Zhengzhou, Henan 450016, China; Corresponding author
Shuyuan Guo
Department of Gastroenterology, Aerospace Center Hospital, College of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China; Corresponding author
Summary: Identifying beneficial or functional mutations for a specific species is a task always relies on the labor-intensive construction of a library containing thousands of single-gene knockout or interference strains. Here, we systematically demonstrated that the task could be done by constructing a genome-scale library, designed by AutoGSL, containing a limited number of large fragment deletion strains. The loss-of- and gain-of-function phenotypes could be efficiently screened out by our chromosome-segment scanning, and the specific gene corresponding to an observed phenotype could be quickly identified and visualized by our computer-aided gene-annotation web tool. Additionally, a Clusters of Orthologous Gene Transformer learned representations were transferred to predict growth phenotypes of the genome-scale library under varying conditions. We further utilized our chromosome segment scanning for gain- or loss-of-function screening (CHASING) strategy to obtain acetoin- and lycopene-overproducing hosts. Our work highlighted the significance of CHASING in functional genomics investigation, robust chassis engineering, and chemical overproduction.
