RT Journal Article SR Electronic T1 FORKS: Finding Orderings Robustly using k-means and Steiner trees JF bioRxiv FD Cold Spring Harbor Laboratory SP 132811 DO 10.1101/132811 A1 Mayank Sharma A1 Huipeng Li A1 Debarka Sengupta A1 Shyam Prabhakar A1 Jayadeva YR 2017 UL http://biorxiv.org/content/early/2017/06/20/132811.abstract AB Recent advances in single cell RNA-seq technologies have provided researchers with unprecedented details of transcriptomic variation across individual cells. However, it has not been straightforward to infer differentiation trajectories from such data, due to the parameter-sensitivity of existing methods. Here, we present Finding Orderings Robustly using k-means and Steiner trees (FORKS), an algorithm that pseudo-temporally orders cells and thereby infers bifurcating state trajectories. FORKS, which is a generic method, can be applied to both single-cell and bulk differentiation data. It is a semi-supervised approach, in that it requires the user to specify the starting point of the time course. We systematically benchmarked FORKS and eight other pseudo-time estimation algorithms on six benchmark datasets, and found it to be more accurate, more reproducible, and more memory-efficient than existing methods for pseudo-temporal ordering. Another major advantage of our approach is its robustness – FORKS can be used with default parameter settings on a wide range of datasets.