Abstract
Single-cell genome sequencing has become a useful tool in medicine and biology studies. However, an independent library is required for each cell in single-cell genome sequencing, so that the cost grows with the number of cells. In this study, we report a study which efficiently analyses single-cell copy number variation (CNV) using overlapping pooling strategy and branch and bound (B&B) algorithm. Single cells were overlapped pooled before sequencing, and later were assorted into specific types by estimating their CNV patterns by B&B algorithm. Instead of constructing libraries for each cell, a library is required only for each pool. As the number of pools is smaller than the cells, fewer libraries are required, which means lower cost. Through computer simulations, we overlapped pooled 80 cells into 40 or 27 pools and classified them into cell types based on CNV pattern. The results showed that 84% cells in 40 pools and 76.5% cells in 27 pools were correctly classified on average, while only half or one-third of the sequencing libraries were required. Combining with traditional approaches, our method is expected to significantly improve the efficiency of single-cell genome sequencing.
Highlights
Genomics variants range from single-nucleotide changes to large chromosomal-level aberrations and can be presented in many forms, including single-nucleotide variations (SNVs), small insertions and deletions (Indels), copy number variations (CNVs), larger structural variants and entire chromosome alteration (Aneuploidy) [1,2]
The results showed that 84% cells in 40 pools and 76.5% in 27 pools could be correctly classified to their origin CNV patterns on average
The results showed that 84% cells in 40 pools and 76.5% cells in 27 pools could be accurately restored to their original CNV types
Summary
Genomics variants range from single-nucleotide changes to large chromosomal-level aberrations and can be presented in many forms, including single-nucleotide variations (SNVs), small insertions and deletions (Indels), copy number variations (CNVs), larger structural variants and entire chromosome alteration (Aneuploidy) [1,2]. CNVs originally represent amplifications and deletions of the fragments of genomics DNA which are greater royalsocietypublishing.org/journal/rsos R. With the development of methodologies, the 2 concept of CNVs is later widened where smaller (50 b–1 kb) amplifications and deletions are included [5]. More and more studies have shown that CNVs confer susceptibility to a variety of human cancers [6,7]. Inter-tumour and intra-tumour heterogeneity pose a great challenge for cancer treatment and recovery [8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
