HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Single-cell DNA sequencing (scDNA-seq) is crucial for understanding somatic cancer variation.
• Current scDNA-seq methods face limitations in throughput and integration with transcriptome sequencing.
• A need exists for scalable, accessible assays to profile both DNA and RNA at the single-cell level.

Purpose of the Study:

• To introduce HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a novel assay for parallel low-coverage DNA and RNA profiling.
• To demonstrate the scalability and accessibility of the HIPSD&R-seq assay.
• To validate the assay's capability in detecting rare cell populations.

Main Methods:

• Modification of the 10X Genomics platform for simultaneous scATAC and multiome profiling.
• Development of a high-throughput assay for low-coverage DNA and RNA sequencing in single cells.
• Application of combinatorial indexing to achieve large-scale cell profiling.

Main Results:

• HIPSD&R-seq successfully profiles low-coverage DNA and RNA in thousands of cells in parallel.
• The assay demonstrated feasibility in human cell models and primary tissues.
• Rare clones were effectively detected using the HIPSD&R-seq method.
• Combinatorial indexing enabled profiling of over 17,000 cells.

Conclusions:

• HIPSD&R-seq offers a scalable, simple, and accessible solution for single-cell DNA and RNA sequencing.
• The assay enables the detection of rare clones, advancing cancer genomics research.
• HIPSD&R-seq integrates DNA and RNA profiling, providing comprehensive single-cell insights.