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For example, in developmental biology, the dynamics of differentiation can now be mapped quantitatively using single-cell RNA sequencing, yet it is difficult to infer molecular regulators of developmental transitions. Here, we show that discovering informative features in the data is crucial for statistical analysis as well as making experimental predictions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identify features based on their ability to discriminate between clusters of the data points. We define a class of problems in which linear separability of clusters is hidden in a low-dimensional space. We propose an unsupervised method to identify the subset of features that define a low-dimensional subspace in which clustering can be conducted. This is achieved by averaging over discriminators trained on an ensemble of proposed cluster configurations. We then apply our method to single-cell RNA-seq data from mouse gastrulation, and identify 27\u2009key transcription factors (out of 409 total), 18 of which are known to define cell states through their expression levels. In this inferred subspace, we find clear signatures of known cell types that eluded classification prior to discovery of the correct low-dimensional subspace.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>https:\/\/github.com\/smelton\/SMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa690","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T19:15:12Z","timestamp":1595531712000},"page":"202-212","source":"Crossref","is-referenced-by-count":14,"title":["Discovering a sparse set of pairwise discriminating features in high-dimensional data"],"prefix":"10.1093","volume":"37","author":[{"given":"Samuel","family":"Melton","sequence":"first","affiliation":[{"name":"Applied Mathematics Harvard University , Cambridge, MA 02138, USA"}]},{"given":"Sharad","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Applied Physics, John A. Paulson School of Engineering and Applied Sciences, Harvard University , Cambridge, MA 02138, USA"},{"name":"Department of Stem Cell and Regenerative Biology , Cambridge, MA 02138, USA"},{"name":"Department of Molecular and Cellular Biology, Harvard University , Cambridge, MA 02138, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"2023051601060156000_btaa690-B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nrm2618","article-title":"Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo","volume":"10","author":"Arnold","year":"2009","journal-title":"Nat. Rev. Mol. 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