PT  - JOURNAL ARTICLE
AU  - Xiaojie Qiu
AU  - Qi Mao
AU  - Ying Tang
AU  - Li Wang
AU  - Raghav Chawla
AU  - Hannah Pliner
AU  - Cole Trapnell
TI  - Reversed graph embedding resolves complex single-cell developmental trajectories
AID  - 10.1101/110668
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 110668
4099  - http://biorxiv.org/content/early/2017/02/21/110668.short
4100  - http://biorxiv.org/content/early/2017/02/21/110668.full
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.