TCM visualizes trajectories and cell populations from single cell data

Profiling single cell gene expression data over specified time periods are increasingly applied to the study of complex developmental processes. Here, we describe a novel prototype-based dimension reduction method to visualize high throughput temporal expression data for single cell analyses. Our software preserves the global developmental trajectories over a specified time course, and it also identifies subpopulations of cells within each time point demonstrating superior visualization performance over six commonly used methods.Time series single cell expression data has large variance between time points and is challenging for analysis. Here, the authors develop a new dimension reduction and data visualization tool for large scale temporal scRNA-seq data which identifies trajectories and subpopulations.

[1]  Fabian J Theis,et al.  Diffusion pseudotime robustly reconstructs lineage branching , 2016, Nature Methods.

[2]  Chong Wang,et al.  Variational inference in nonconjugate models , 2012, J. Mach. Learn. Res..

[3]  Paul Theodor Pyl,et al.  HTSeq—a Python framework to work with high-throughput sequencing data , 2014, bioRxiv.

[4]  Fabian J Theis,et al.  Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells , 2015, Nature Biotechnology.

[5]  E. Pierson,et al.  ZIFA: Dimensionality reduction for zero-inflated single-cell gene expression analysis , 2015, Genome Biology.

[6]  Caleb Webber,et al.  Laplacian eigenmaps and principal curves for high resolution pseudotemporal ordering of single-cell RNA-seq profiles , 2015, bioRxiv.

[7]  M. V. Velzen,et al.  Self-organizing maps , 2007 .

[8]  Samira M. Azarin,et al.  Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling , 2012, Proceedings of the National Academy of Sciences.

[9]  Andrew J. Hill,et al.  Single-cell mRNA quantification and differential analysis with Census , 2017, Nature Methods.

[10]  Sean C. Bendall,et al.  Wishbone identifies bifurcating developmental trajectories from single-cell data , 2016, Nature Biotechnology.

[11]  Mikael Huss,et al.  Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. , 2010, Developmental cell.

[12]  Masayuki Yamamoto,et al.  GATA1 Function, a Paradigm for Transcription Factors in Hematopoiesis , 2005, Molecular and Cellular Biology.

[13]  W. Huber,et al.  which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets , 2011 .

[14]  Hans Clevers,et al.  Single-cell messenger RNA sequencing reveals rare intestinal cell types , 2015, Nature.

[15]  Michael I. Jordan,et al.  An Introduction to Variational Methods for Graphical Models , 1999, Machine Learning.

[16]  Sarah A. Teichmann,et al.  Temporal mixture modelling of single-cell RNA-seq data resolves a CD4+ T cell fate bifurcation , 2016, bioRxiv.

[17]  P. Kharchenko,et al.  Bayesian approach to single-cell differential expression analysis , 2014, Nature Methods.

[18]  Alex A. Pollen,et al.  Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex , 2014, Nature Biotechnology.

[19]  Ali Taylan Cemgil,et al.  Bayesian Inference for Nonnegative Matrix Factorisation Models , 2009, Comput. Intell. Neurosci..

[20]  Fabian J Theis,et al.  The Human Cell Atlas , 2017, bioRxiv.

[21]  Wuming Gong,et al.  Dpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis , 2017, Nature Communications.

[22]  Allon M. Klein,et al.  Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells , 2015, Cell.

[23]  N. Neff,et al.  Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq , 2016, Nature.

[24]  J. Hartigan,et al.  The Dip Test of Unimodality , 1985 .

[25]  Christopher M. Bishop,et al.  GTM: The Generative Topographic Mapping , 1998, Neural Computation.

[26]  Eric D. Adler,et al.  Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population , 2008, Nature.

[27]  Russell B. Fletcher,et al.  Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics , 2017, BMC Genomics.

[28]  F. Tang,et al.  The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells , 2015, Cell.

[29]  Alvaro Plaza Reyes,et al.  Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos , 2016, Cell.

[30]  David R. Kelley,et al.  Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks , 2012, Nature Protocols.

[31]  Sandy L. Klemm,et al.  Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase , 2012, Cell.

[32]  Hongkai Ji,et al.  TSCAN: Pseudo-time reconstruction and evaluation in single-cell RNA-seq analysis , 2016, Nucleic acids research.

[33]  F. Tang,et al.  Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing , 2013, Genome research.

[34]  Geoffrey E. Hinton,et al.  Visualizing Data using t-SNE , 2008 .

[35]  D. Thieffry Faculty Opinions recommendation of Decoding the regulatory network of early blood development from single-cell gene expression measurements. , 2017 .

[36]  Matthew D. Hoffman,et al.  Beta Process Non-negative Matrix Factorization with Stochastic Structured Mean-Field Variational Inference , 2014, ArXiv.

[37]  Nicola K. Wilson,et al.  Resolving Early Mesoderm Diversification through Single Cell Expression Profiling , 2016, Nature.

[38]  Cole Trapnell,et al.  The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells , 2014, Nature Biotechnology.

[39]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[40]  R. Sandberg,et al.  Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells , 2014, Science.

[41]  Pang Wei Koh,et al.  Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types , 2016, Cell.

[42]  Rona S. Gertner,et al.  Single cell RNA Seq reveals dynamic paracrine control of cellular variation , 2014, Nature.