Eleven grand challenges in single-cell data science

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Metrics details. The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands—or even millions—of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems.

Here, we outline eleven challenges that will be central to bringing this emerging field of single-cell data science forward. For each challenge, we highlight motivating research questions, review prior work, and formulate open problems. This compendium is for established researchers, newcomers, and students alike, highlighting interesting and rewarding problems for the coming years.

Single-cell measurements of both RNA and DNA, and more recently also of epigenetic marks and protein levels, can stratify cells at the finest resolution possible. Single-cell RNA sequencing scRNA-seq enables transcriptome-wide gene expression measurement at single-cell resolution, allowing for cell type clusters to be distinguished for an early example, see [ 2 ] , the arrangement of populations of cells according to novel hierarchies, and the identification of cells transitioning between states.

This can lead to a much clearer view of the dynamics of tissue and organism development, and on structures within cell populations that had so far been perceived as homogeneous. The opportunities arising from single-cell sequencing sc-seq are enormous: only now is it possible to re-evaluate hypotheses about differences between pre-defined sample groups at the single-cell level—no matter if such sample groups are disease subtypes, treatment groups, or simply morphologically distinct cell types.

It is therefore no surprise that enthusiasm about the possibility to screen the genetic material of the basic units of life has continued to grow. A prominent example is the Human Cell Atlas [ 5 ], an initiative aiming to map the numerous cell types and states comprising a human being. Encouraged by the great potential of investigating DNA and RNA at the single-cell level, the development of the corresponding experimental technologies has experienced considerable growth.

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