Modern developments in single cell sequencing technologies enable broad insights into cellular state. Single cell RNA sequencing (scRNA-seq) can be used to explore cell types, states, and developmental trajectories to broaden understanding of cell heterogeneity in tissues and organs. Analysis of these sparse, high-dimensional experimental results requires dimension reduction. Several methods have been developed to estimate low-dimensional embeddings for filtered and normalized single cell data. However, methods have yet to be developed for unfiltered and unnormalized count data. We present a nonlinear latent variable model with robust, heavy-tailed error and adaptive kernel learning to estimate low-dimensional nonlinear structure in scRNA-seq data. Gene expression in a single cell is modeled as a noisy draw from a Gaussian process in high dimensions from low-dimensional latent positions. This model is called the Gaussian process latent variable model (GPLVM). We model residual errors with a heavy-tailed Student's t-distribution to estimate a manifold that is robust to technical and biological noise. We compare our approach to common dimension reduction tools to highlight our model's ability to enable important downstream tasks, including clustering and inferring cell developmental trajectories, on available experimental data. We show that our robust nonlinear manifold is well suited for raw, unfiltered gene counts from high throughput sequencing technologies for visualization and exploration of cell states.
- Downloaded 1,593 times
- Download rankings, all-time:
- Site-wide: 5,287 out of 89,211
- In genomics: 879 out of 5,693
- Year to date:
- Site-wide: 9,349 out of 89,211
- Since beginning of last month:
- Site-wide: 15,869 out of 89,211
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!