Invited Presentation 44th Lorne Genome Conference 2023

Invited Speaker Presentation - scONE-seq: A versatile single-cell multi-omics method for simultaneous dissection of phenotype and genotype heterogeneity from frozen tumors   (#42)

Angela Wu 1 , Lei Yu 2 , Xinlei Wang 2 , Quanhua Mu 3 , Sindy ST Tam 2 , Danson Shek Chun Loi 2 , Aden K.Y Chan 4 , Wai Sang Poon 5 , Ho-Keung Ng 4 , Danny T.M Chan 6 , Jiguang Wang 2 3 7 8 , Angela Ruohao Wu 2 3 9 10
  1. Hong Kong University of Science and Technology, Clear Water Bay, NEW TERRITORIES, Hong Kong
  2. Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, , Hong Kong S.A.R., China
  3. Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, , Hong Kong S.A.R., China
  4. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin, New Territories, , Hong Kong S.A.R., China
  5. Department of Surgery, The Chinese University of Hong Kong, , Hong Kong S.A.R., China.
  6. Department of Surgery, The Chinese University of Hong Kong, Hong Kong S.A.R., China., Hong Kong S.A.R., China.
  7. Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, , Hong Kong S.A.R., China
  8. State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, , Hong Kong S.A.R., China
  9. Hong Kong Branch of Guangdong Southern Marine Science and Engineering Laboratory (Guangzhou), The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, , Hong Kong S.A.R., China
  10. Center for Aging Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, , Hong Kong S.A.R., China

Abstract:

Single-cell multi-omics can provide a unique perspective on tumor cellular heterogeneity. Most previous single-cell-whole-genome-RNA-sequencing (scWGS-RNA-seq) methods demonstrate utility with intact cells from fresh samples. Among them, most are not applicable to frozen samples that cannot generate intact single-cell suspensions. We have developed scONE-seq, a versatile scWGS-RNA-seq method that amplifies single-cell DNA and RNA without separating them from each other. Compared with existing methods, scONE-seq is a one-tube reaction that eliminates loss due to DNA and RNA separation and thus is compatible with frozen biobanked tissue. We applied it to analyze a 2-year-frozen astrocytoma sample and identified a unique transcriptionally normal-like tumor clone. scONE-seq makes it possible to perform single-cell multi-omics interrogation on the vast quantities of biobanked tissue, to this end we have also developed a droplet array platform for implementing multi-step single-cell reactions at scale.