RT Journal Article
SR Electronic
T1 Reversed graph embedding resolves complex single-cell developmental trajectories
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 110668
DO 10.1101/110668
A1 Xiaojie Qiu
A1 Qi Mao
A1 Ying Tang
A1 Li Wang
A1 Raghav Chawla
A1 Hannah Pliner
A1 Cole Trapnell
YR 2017
UL http://biorxiv.org/content/early/2017/02/21/110668.abstract
AB Organizing single cells along a developmental trajectory has emerged as a powerful tool for understanding how gene regulation governs cell fate decisions. However, learning the structure of complex single-cell trajectories with two or more branches remains a challenging computational problem. We present Monocle 2, which uses reversed graph embedding to reconstruct single-cell trajectories in a fully unsupervised manner. Monocle 2 learns an explicit principal graph to describe the data, greatly improving the robustness and accuracy of its trajectories compared to other algorithms. Monocle 2 uncovered a new, alternative cell fate in what we previously reported to be a linear trajectory for differentiating myoblasts. We also reconstruct branched trajectories for two studies of blood development, and show that loss of function mutations in key lineage transcription factors diverts cells to alternative branches on the a trajectory. Monocle 2 is thus a powerful tool for analyzing cell fate decisions with single-cell genomics.