Single-cell analyses to tailor treatments

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Abstract

Single-cell RNA-seq could play a key role in personalized medicine by facilitating characterization of cells, pathways, and genes associated with human diseases such as cancer.

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Most cited references 7

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Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses

Yonit Lavin, Soma Kobayashi, Andrew Leader … (2017)

To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single cell analysis of the tumor, non-involved lung and blood cells together with multiplex tissue imaging to assess spatial cell distribution, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. Comparing single tumor cells with adjacent normal tissue and blood from patients with lung adenocarcinoma charts early changes in tumor immunity and provides insights to guide immunotherapy design.

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Seq-Well: A Portable, Low-Cost Platform for High-Throughput Single-Cell RNA-Seq of Low-Input Samples

Todd M. Gierahn, Marc Wadsworth, Travis K. Hughes … (2017)

Single-cell RNA-Seq can precisely resolve cellular states but application to sparse samples is challenging. Here, we present Seq-Well, a portable, low-cost platform for massively-parallel single-cell RNA-Seq. Barcoded mRNA capture beads and single cells are sealed in an array of subnanoliter wells using a semi-permeable membrane, enabling efficient cell lysis and transcript capture. We characterize Seq-Well using species-mixing experiments and PBMCs, and profile thousands of primary human macrophages exposed to tuberculosis.

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Precision oncology for acute myeloid leukemia using a knowledge bank approach

Moritz Gerstung, Elli Papaemmanuil, Inigo Martincorena … (2017)

Peter Campbell, Hartmut Döhner and colleagues present an analysis of genetic mutations and clinical information from 1,540 patients with acute myeloid leukemia, demonstrating the utility of clinical knowledge banks for personalized medicine. They show that use of their approach could reduce the number of hematopoietic cell transplants in patients with AML by up to 25% while maintaining survival rates.