Optimizing sparse sequencing of single cells for highly multiplex copy number profiling

Baslan, Timour; Kendall, Jude; Ward, Brian; Cox, Hilary; Leotta, Anthony; Rodgers, Linda; Riggs, Michael; D'Italia, Sean; Sun, Guoli; Mao, Yong; Miskimen, Kristy; Gilmore, Hannah; Saborowski, Michael; Dimitrova, Nevenka; Krasnitz, Alexander; Harris, Lyndsay N.; Wigler, Michael; Hicks, James

doi:10.1101/gr.188060.114

Cited by 119 publications

(122 citation statements)

References 38 publications

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“…This is now possible on a single cell basis at the level of whole genome copy number analysis (63)(64)(65)(66)(67). Combined with morphologic analysis of CTCs, the addition of genomic analysis provides a capacity to study cancer populations as a collection of individual cells, often revealing cancers to be oligoclonal proliferations of cancer cells, rather than truly clonal populations possessing a singular genome (68).…”

Section: Future Technologies For Tumor Characterization Of Ctcsmentioning

confidence: 99%

Biophysical technologies for understanding circulating tumor cell biology and metastasis

Nieva

2017

Transl. Lung Cancer Res.

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An understanding of cancer evolution in lung cancer with its associated resistance to therapy can only be achieved with repeated sampling and analysis of the cancer. Given the high risks and costs associated with repeat physical biopsy, alternative technologies must be applied. Several modalities exist for analysis and re-analysis of cancer biology. Among them are the CellSearch platform, the CTC chip, and the highdefinition CTC platform. While the former is primarily able to provide prognosticating information in the form of CTC enumeration, the latter two have the advantage of serving as a platform to study tumor biology. Techniques for analysis of single cell genomics, as well as protein expression on a single cell basis provide scientists with the capacity to understand cancer cell populations as a collection of individual cells, rather than as an average of all cells. A multimodal combination of circulating tumor DNAs (ctDNAs), CTCs, proteomics, and CTC-derived xenografts (CDXs) to create computational models useful in diagnosis, prognostication, and predictiveness to treatment is likely the future of tailoring individualized cancer care.

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Section: Future Technologies For Tumor Characterization Of Ctcsmentioning

confidence: 99%

Biophysical technologies for understanding circulating tumor cell biology and metastasis

Nieva

2017

Transl. Lung Cancer Res.

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“…To address these issues, several studies have begun to develop multiplexing strategies for SCS experiments. A recent method, called C-DOP-P, uses 96 barcodes to improve multiplexing of SNS and increase the throughput for single-cell copy number profiling (Baslan et al 2015). Commercial microfluidic approaches such as the Fluidigm C1 system have also been developed for analyzing 96 single-cell RNA profiles in parallel using nanoliter reaction volumes.…”

Section: Technical Challenges and Emerging Technologiesmentioning

confidence: 99%

The first five years of single-cell cancer genomics and beyond

2015

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Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five years, there has been extraordinary progress in technological developments and research applications, but these efforts represent only the tip of the iceberg. In the coming years, SCS will greatly improve our understanding of invasion, metastasis, and therapy resistance during cancer progression. These tools will also have direct translational applications in the clinic, in areas such as early detection, noninvasive monitoring, and guiding targeted therapy. In this perspective, I discuss the progress that has been made and the myriad of unexplored applications that still lie ahead in cancer research and medicine.

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“…Single cell genome sequencing studies have taken one of two approaches: high depth of sequencing per cell for purposes of single nucleotide variant detection 2,8 , or low-pass sequencing to identify copy number variants (CNVs) and the presence of aneuploidy 1,9,10 . In the latter approach, the lack of a method to cost-effectively produce high numbers of single cell libraries has prevented the ability to quantitatively measure the frequency of CNV-harboring cells at population-level scale, or provide a robust analysis of heterogeneity in the context of cancer 11 .…”

Section: Introductionmentioning

confidence: 99%

Construction of thousands of single cell genome sequencing libraries using combinatorial indexing

Vitak

Torkenczy

Rosenkrantz

et al. 2016

Preprint

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Single cell genome sequencing has proven to be a valuable tool for the detection of somatic variation, particularly in the context of tumor evolution and neuronal heterogeneity. Current technologies suffer from high per-cell library construction costs which restrict the number of cells that can be assessed, thus imposing limitations on the ability to quantitatively measure genomic heterogeneity within a tissue. Here, we present Single cell Combinatorial Indexed Sequencing (SCI-seq) as a means of simultaneously generating thousands of low-pass single cell libraries for the purpose of somatic copy number variant detection. In total, we constructed libraries for 16,698 single cells from a combination of cultured cell lines, frontal cortex tissue from Macaca mulatta, and two human adenocarcinomas. This novel technology provides the opportunity for low-cost, deep characterization of somatic copy number variation in single cells, providing a foundational knowledge across both healthy and diseased tissues.peer-reviewed)

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Optimizing sparse sequencing of single cells for highly multiplex copy number profiling

Cited by 119 publications

References 38 publications

Biophysical technologies for understanding circulating tumor cell biology and metastasis

Biophysical technologies for understanding circulating tumor cell biology and metastasis

The first five years of single-cell cancer genomics and beyond

Construction of thousands of single cell genome sequencing libraries using combinatorial indexing

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