RT Journal Article SR Electronic T1 The Specious Art of Single-Cell Genomics JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.08.25.457696 DO 10.1101/2021.08.25.457696 A1 Chari, Tara A1 Banerjee, Joeyta A1 Pachter, Lior YR 2021 UL http://biorxiv.org/content/early/2021/08/26/2021.08.25.457696.abstract AB Dimensionality reduction is standard practice for filtering noise and identifying relevant dimensions in large-scale data analyses. In biology, single-cell expression studies almost always begin with reduction to two or three dimensions to produce ‘all-in-one’ visuals of the data that are amenable to the human eye, and these are subsequently used for qualitative and quantitative analysis of cell relationships. However, there is little theoretical support for this practice. We examine the theoretical and practical implications of low-dimensional embedding of single-cell data, and find extensive distortions incurred on the global and local properties of biological patterns relative to the high-dimensional, ambient space. In lieu of this, we propose semi-supervised dimension reduction to higher dimension, and show that such targeted reduction guided by the metadata associated with single-cell experiments provides useful latent space representations for hypothesis-driven biological discovery.Competing Interest StatementThe authors have declared no competing interest.